Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Embryo-Maternal Interactions Underlying Reproduction in Mammals
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Embryo-Maternal Interactions Underlying Reproduction in Mammals

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (29 November 2019) | Viewed by 134854

Special Issue Editors

Dr. Stefan Bauersachs

E-Mail Website
Guest Editor
Vetsuisse Faculty Zurich, University of Zurich, Eschikon 27, AgroVet-Strickhof, 8315 Lindau, Switzerland
Interests: endometrium; embryo; extracellular vesicles/exosomes; preimplantation phase; sperm miRNAs; gene expression; transcriptomics; RNA-sequencing; microRNA; bioinformatics
Dr. Carmen Almiñana

E-Mail Website
Guest Editor
Vetsuisse Faculty Zurich, University of Zurich, Eschikon 27, AgroVet-Strickhof, 8315 Lindau (ZH), Switzerland
Interests: oviduct; endometrium; embryo; extracellular vesicles/exosomes; preimplantation phase; gene expression; transcriptomics; reproductive biotechnologies; in vitro embryo production; embryo cryopreservation

Special Issue Information

Dear Colleagues,

This Special Issue, “Embryo-Maternal Interactions Underlying Reproduction in Mammals”, will include a selection of recent research topics and current review articles related to the study of embryo-maternal interactions in mammalian species during the preimplantation phase. Up-to-date review articles, commentaries as well as original experimental papers are welcome. Since the reproductive strategies show considerable differences between mammalian groups, articles are not restricted to a specific mammalian species and comparative approaches among species are also welcome.

For the last two decades, omics technologies have revolutionized the study of embryo-maternal interactions and revealed an unexpected complexity and diversity of this dialog among mammals. Differences have been identified regarding the maternal support of embryo development, recognition of pregnancy, and preparation for implantation. Studies have been performed on all players involved in these interactions; embryos at different stages, oviduct, endometrium, and more recently oviductal and endometrial fluid including extracellular vesicles/exosomes contained in these fluids. Particularly, the latter have been proposed as modulators of the maternal-embryo dialogue by the exchange of various types of molecules (RNAs, proteins, lipids, and other metabolites) and also as an epigenetic mechanism for the transfer of these maternal molecules to the early embryo.

Dr. Stefan Bauersachs
Dr. Carmen Almiñana
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • oviduct
  • endometrium
  • embryo
  • conceptus
  • extracellular vesicles/exosomes
  • preimplantation phase
  • maternal recognition of pregnancy
  • implantation
  • transcriptomics
  • proteomics

Published Papers (24 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

6 pages, 524 KiB  
Editorial
Embryo–Maternal Interactions Underlying Reproduction in Mammals
by Stefan Bauersachs and Carmen Almiñana
Int. J. Mol. Sci. 2020, 21(14), 4872; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21144872 - 10 Jul 2020
Cited by 3 | Viewed by 2497
Abstract
This Special Issue, “Embryo-Maternal Interactions Underlying Reproduction in Mammals”, gathers a collection of 23 articles, 16 original research articles and 7 up-to-date reviews, providing new findings or summarizing current knowledge on embryo–maternal interactions in seven different mammalian species including humans. Considering the different [...] Read more.
This Special Issue, “Embryo-Maternal Interactions Underlying Reproduction in Mammals”, gathers a collection of 23 articles, 16 original research articles and 7 up-to-date reviews, providing new findings or summarizing current knowledge on embryo–maternal interactions in seven different mammalian species including humans. Considering the different players involved in these embryo-maternal interactions, articles are mainly focused on one of these different players: the oviduct, the uterus, the embryo or the emergent extracellular vesicles. Additionally, a few articles bring up the impact of reproductive, but also non-reproductive, diseases, as well as stress factors, on the establishment of pregnancy. We hope the readers enjoy this collection of articles and that the knowledge assembled here will support and inspire current and future research investigations. We would like to thank all authors for their contributions to this Special Issue. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

Research

Jump to: Editorial, Review

19 pages, 1509 KiB  
Article
Protein Synthesis by Day 16 Bovine Conceptuses during the Time of Maternal Recognition of Pregnancy
by Irene Malo Estepa, Haidee Tinning, Elton Jóse Rosas Vasconcelos, Beatriz Fernandez-Fuertes, José María Sánchez, Gregory W. Burns, Thomas E. Spencer, Pat Lonergan and Niamh Forde
Int. J. Mol. Sci. 2020, 21(8), 2870; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082870 - 20 Apr 2020
Cited by 12 | Viewed by 3770
Abstract
Interferon Tau (IFNT), the conceptus-derived pregnancy recognition signal in cattle, significantly modifies the transcriptome of the endometrium. However, the endometrium also responds to IFNT-independent conceptus-derived products. The aim of this study was to determine what proteins are produced by the bovine conceptus that [...] Read more.
Interferon Tau (IFNT), the conceptus-derived pregnancy recognition signal in cattle, significantly modifies the transcriptome of the endometrium. However, the endometrium also responds to IFNT-independent conceptus-derived products. The aim of this study was to determine what proteins are produced by the bovine conceptus that may facilitate the pregnancy recognition process in cattle. We analysed by mass spectrometry the proteins present in conceptus-conditioned media (CCM) after 6 h culture of Day 16 bovine conceptuses (n = 8) in SILAC media (arginine- and lysine-depleted media supplemented with heavy isotopes) and the protein content of extracellular vesicles (EVs) isolated from uterine luminal fluid (ULF) of Day 16 pregnant (n = 7) and cyclic (n = 6) cross-bred heifers on day 16. In total, 11,122 proteins were identified in the CCM. Of these, 5.95% (662) had peptides with heavy labelled amino acids, i.e., de novo synthesised by the conceptuses. None of these proteins were detected in the EVs isolated from ULF. Pregnancy-associated glycoprotein 11, Trophoblast Kunitz domain protein 1 and DExD-Box Helicase 39A were de novo produced and present in the CCM from all conceptuses and in previously published CCM data following 6 and 24 h. A total of 463 proteins were present in the CCM from all the conceptuses in the present study, and after 6 and 24 h culture in a previous study, while expression of their transcripts was not detected in endometrium indicating that they are likely conceptus-derived. Of the proteins present in the EVs, 67 were uniquely identified in ULF from pregnant heifers; 35 of these had been previously reported in CCM from Day 16 conceptuses. This study has narrowed a set of conceptus-derived proteins that may be involved in EV-mediated IFNT-independent embryo–maternal communication during pregnancy recognition in cattle. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

25 pages, 3112 KiB  
Article
Asynchronous Embryo Transfer Followed by Comparative Transcriptomic Analysis of Conceptus Membranes and Endometrium Identifies Processes Important to the Establishment of Equine Pregnancy
by Charlotte Gibson, Marta de Ruijter-Villani, Stefan Bauersachs and Tom A.E. Stout
Int. J. Mol. Sci. 2020, 21(7), 2562; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072562 - 07 Apr 2020
Cited by 8 | Viewed by 2983
Abstract
Preimplantation horse conceptuses require nutrients and signals from histotroph, the composition of which is regulated by luteal progesterone and conceptus-secreted factors. To distinguish progesterone and conceptus effects we shortened the period of endometrial progesterone-priming by asynchronous embryo transfer. Day 8 embryos were transferred [...] Read more.
Preimplantation horse conceptuses require nutrients and signals from histotroph, the composition of which is regulated by luteal progesterone and conceptus-secreted factors. To distinguish progesterone and conceptus effects we shortened the period of endometrial progesterone-priming by asynchronous embryo transfer. Day 8 embryos were transferred to synchronous (day 8) or asynchronous (day 3) recipients, and RNA sequencing was performed on endometrium and conceptuses recovered 6 and 11 days later (embryo days 14 and 19). Asynchrony resulted in many more differentially expressed genes (DEGs) in conceptus membranes (3473) than endometrium (715). Gene ontology analysis identified upregulation in biological processes related to organogenesis and preventing apoptosis in synchronous conceptuses on day 14, and in cell adhesion and migration on day 19. Asynchrony also resulted in large numbers of DEGs related to ‘extracellular exosome’. In endometrium, genes involved in immunity, the inflammatory response, and apoptosis regulation were upregulated during synchronous pregnancy and, again, many genes related to extracellular exosome were differentially expressed. Interestingly, only 14 genes were differentially expressed in endometrium recovered 6 days after synchronous versus 11 days after asynchronous transfer (day 14 recipient in both). Among these, KNG1 and IGFBP3 were consistently upregulated in synchronous endometrium. Furthermore bradykinin, an active peptide cleaved from KNG1, stimulated prostaglandin release by cultured trophectoderm cells. The horse conceptus thus responds to a negatively asynchronous uterus by extensively adjusting its transcriptome, whereas the endometrial transcriptome is modified only subtly by a more advanced conceptus. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

19 pages, 4010 KiB  
Article
Spatial and Pregnancy-Related Changes in the Protein, Amino Acid, and Carbohydrate Composition of Bovine Oviduct Fluid
by Beatriz Rodríguez-Alonso, Veronica Maillo, Omar Salvador Acuña, Rebeca López-Úbeda, Alejandro Torrecillas, Constantine A. Simintiras, Roger Sturmey, Manuel Avilés, Patrick Lonergan and Dimitrios Rizos
Int. J. Mol. Sci. 2020, 21(5), 1681; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051681 - 29 Feb 2020
Cited by 14 | Viewed by 4404
Abstract
Knowledge of how the biochemical composition of the bovine oviduct is altered due to the oviduct anatomy or the presence of an embryo is lacking. Thus, the aim of this study was to assess the effect of (І) oviduct anatomy and (ІІ) embryo [...] Read more.
Knowledge of how the biochemical composition of the bovine oviduct is altered due to the oviduct anatomy or the presence of an embryo is lacking. Thus, the aim of this study was to assess the effect of (І) oviduct anatomy and (ІІ) embryo presence on oviductal fluid (OF) protein, amino acid, and carbohydrate composition. Cross-bred beef heifers (n = 19) were synchronized and those in standing estrus were randomly allocated to a cyclic (non-bred) or pregnant (artificially inseminated) group. All heifers were slaughtered on Day 3 after estrus. The oviducts ipsilateral to the corpus luteum from each animal were isolated, straightened and cut, separating ampulla and isthmus. Each portion was flushed with 500 µl of PBS enabling recovery of the oocyte/embryo. Recovered unfertilized oocytes (cyclic group) and embryos (8-cell embryos; pregnant group) were located in the isthmus of the oviduct. Samples of flushing medium from the isthmus and ampulla were used for proteomic (n = 2 per group), amino acid (n = 5), and carbohydrate (n = 5) analysis. For proteomic analysis, total protein from cyclic and pregnant samples were labelled with different cyanine fluorescent probes and separated according to the isoelectric point using immobilized pH gradient strips (pH 3–10, 17 cm, Protean® IEF cell system, Bio Rad). Second dimension was performed in a polyacrylamide gel (12%) in the presence of SDS using a Protean II XL system (Bio Rad). Images were obtained with a Typhoon 9410 scanner and analyzed with Progenesis SameSpots software v 4.0. Amino acid content in the OF was determined by high performance liquid chromatography (HPLC). Glucose, lactate, and pyruvate were quantified using microfluorometric enzyme-linked assays. For the proteomic assessment, the results of the image analysis were compared by ANOVA. For both amino acid and carbohydrate analyses, statistical analysis was carried out by 2-way ANOVA with the Holm-Sidak nonparametric post hoc analysis. On Day 3 post-estrus, OF composition varied based on (І) anatomical region, where isthmic metabolites were present in lower (i.e., lactate, glycine, and alanine) or higher (i.e., arginine) concentrations compared to the ampulla; and (ІІ) embryo presence, which was correlated with greater, arginine, phosphoglycerate kinase 1, serum albumin, α-1-antiproteinase and IGL@ protein concentrations. In conclusion, data indicate that the composition of bovine OF is anatomically dynamic and influenced by the presence of an early embryo. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

10 pages, 2541 KiB  
Article
Initiation of Conceptus Elongation Coincides with an Endometrium Basic Fibroblast Growth Factor (FGF2) Protein Increase in Heifers
by Daniel Chiumia, Katy Schulke, Anna E. Groebner, Nadine Waldschmitt, Horst-Dieter Reichenbach, Valeri Zakhartchenko, Stefan Bauersachs and Susanne E. Ulbrich
Int. J. Mol. Sci. 2020, 21(5), 1584; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051584 - 26 Feb 2020
Cited by 7 | Viewed by 2361
Abstract
Fibroblast growth factors (FGF) play an important role during embryo development. To date, the role of FGF and the respective receptors (FGFR) during the preimplantation phase in cattle are not fully characterized. We examined FGF1, FGF2, FGFR1, FGFR2, and FGFR3 in cyclic and [...] Read more.
Fibroblast growth factors (FGF) play an important role during embryo development. To date, the role of FGF and the respective receptors (FGFR) during the preimplantation phase in cattle are not fully characterized. We examined FGF1, FGF2, FGFR1, FGFR2, and FGFR3 in cyclic and early pregnant heifers at Days 12, 15, and 18 after insemination (Day 0). Endometrial FGF1 mRNA transcript abundance in heifers varied significantly with respect to the day after insemination, the pregnancy status, and their interaction. The expression was higher in nonpregnant than in pregnant heifers at Day 18. The conceptus transcripts abundance of FGFR2 and FGFR3 were significantly lower at Day 15 than 18. In the endometrium, FGF1 protein abundance significantly decreased from Day 12 onwards and FGF2 protein abundance showed a minor, but a significant increase at Day 15 in comparison to Days 12 and 18. We concluded that the decrease in FGF1 mRNA expression in pregnant heifers at Day 18 points towards a potential contribution of FGF1 in the preimplantation process. Additionally, successful embryo elongation might require a spatiotemporal FGF2 protein increase in the endometrium. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

17 pages, 2693 KiB  
Article
FOXL2 is a Progesterone Target Gene in the Endometrium of Ruminants
by Caroline Eozenou, Audrey Lesage-Padilla, Vincent Mauffré, Gareth D. Healey, Sylvaine Camous, Philippe Bolifraud, Corinne Giraud-Delville, Daniel Vaiman, Takashi Shimizu, Akio Miyamoto, Iain Martin Sheldon, Fabienne Constant, Maëlle Pannetier and Olivier Sandra
Int. J. Mol. Sci. 2020, 21(4), 1478; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041478 - 21 Feb 2020
Cited by 10 | Viewed by 3313
Abstract
Forkhead Box L2 (FOXL2) is a member of the FOXL class of transcription factors, which are essential for ovarian differentiation and function. In the endometrium, FOXL2 is also thought to be important in cattle; however, it is not clear how its expression is [...] Read more.
Forkhead Box L2 (FOXL2) is a member of the FOXL class of transcription factors, which are essential for ovarian differentiation and function. In the endometrium, FOXL2 is also thought to be important in cattle; however, it is not clear how its expression is regulated. The maternal recognition of pregnancy signal in cattle, interferon-Tau, does not regulate FOXL2 expression. Therefore, in the present study, we examined whether the ovarian steroid hormones that orchestrate implantation regulate FOXL2 gene expression in ruminants. In sheep, we confirmed that FOXL2 mRNA and protein was expressed in the endometrium across the oestrous cycle (day 4 to day 15 post-oestrus). Similar to the bovine endometrium, ovine FOXL2 endometrial expression was low during the luteal phase of the oestrous cycle (4 to 12 days post-oestrus) and at implantation (15 days post-oestrus) while mRNA and protein expression significantly increased during the luteolytic phase (day 15 post-oestrus in cycle). In pregnant ewes, inhibition of progesterone production by trilostane during the day 5 to 16 period prevented the rise in progesterone concentrations and led to a significant increase of FOXL2 expression in caruncles compared with the control group (1.4-fold, p < 0.05). Ovariectomized ewes or cows that were supplemented with exogenous progesterone for 12 days or 6 days, respectively, had lower endometrial FOXL2 expression compared with control ovariectomized females (sheep, mRNA, 1.8-fold; protein, 2.4-fold; cattle; mRNA, 2.2-fold; p < 0.05). Exogenous oestradiol treatments for 12 days in sheep or 2 days in cattle did not affect FOXL2 endometrial expression compared with control ovariectomized females, except at the protein level in both endometrial areas in the sheep. Moreover, treating bovine endometrial explants with exogenous progesterone for 48h reduced FOXL2 expression. Using in vitro assays with COS7 cells we also demonstrated that progesterone regulates the FOXL2 promoter activity through the progesterone receptor. Collectively, our findings imply that endometrial FOXL2 is, as a direct target of progesterone, involved in early pregnancy and implantation. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

31 pages, 3915 KiB  
Article
The Oviductal Extracellular Vesicles’ RNA Cargo Regulates the Bovine Embryonic Transcriptome
by Stefan Bauersachs, Pascal Mermillod and Carmen Almiñana
Int. J. Mol. Sci. 2020, 21(4), 1303; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041303 - 14 Feb 2020
Cited by 30 | Viewed by 3815
Abstract
Oviductal extracellular vesicles (oEVs) are emerging as key players in the gamete/embryo–oviduct interactions that contribute to successful pregnancy. Various positive effects of oEVs on gametes and early embryos have been found in vitro. To determine whether these effects are associated with changes of [...] Read more.
Oviductal extracellular vesicles (oEVs) are emerging as key players in the gamete/embryo–oviduct interactions that contribute to successful pregnancy. Various positive effects of oEVs on gametes and early embryos have been found in vitro. To determine whether these effects are associated with changes of embryonic gene expression, the transcriptomes of embryos supplemented with bovine fresh (FeEVs) or frozen (FoEVs) oEVs during in vitro culture compared to controls without oEVs were analyzed by low-input RNA sequencing. Analysis of RNA-seq data revealed 221 differentially expressed genes (DEGs) between FoEV treatment and control, 67 DEGs for FeEV and FoEV treatments, and minor differences between FeEV treatment and control (28 DEGs). An integrative analysis of mRNAs and miRNAs contained in oEVs obtained in a previous study with embryonic mRNA alterations pointed to direct effects of oEV cargo on embryos (1) by increasing the concentration of delivered transcripts; (2) by translating delivered mRNAs to proteins that regulate embryonic gene expression; and (3) by oEV-derived miRNAs which downregulate embryonic mRNAs or modify gene expression in other ways. Our study provided the first high-throughput analysis of the embryonic transcriptome regulated by oEVs, increasing our knowledge on the impact of oEVs on the embryo and revealing the oEV RNA components that potentially regulate embryonic development. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

21 pages, 1317 KiB  
Article
Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits
by Maria Schindler, Sophia Mareike Pendzialek, Katarzyna Grybel, Tom Seeling and Anne Navarrete Santos
Int. J. Mol. Sci. 2020, 21(3), 919; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21030919 - 30 Jan 2020
Cited by 6 | Viewed by 3214
Abstract
Metabolic disorders of the mother adversely affect early embryo development, causing changes in maternal metabolism and consequent alterations in the embryo environment in the uterus. The goal of this study was to analyse the biochemical profiles of embryonic fluids and blood plasma of [...] Read more.
Metabolic disorders of the mother adversely affect early embryo development, causing changes in maternal metabolism and consequent alterations in the embryo environment in the uterus. The goal of this study was to analyse the biochemical profiles of embryonic fluids and blood plasma of rabbits with and without insulin-dependent diabetes mellitus (DT1), to identify metabolic changes associated with maternal diabetes mellitus in early pregnancy. Insulin-dependent diabetes was induced by alloxan treatment in female rabbits 10 days before mating. On day 6 post-coitum, plasma and blastocoel fluid (BF) were analysed by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) (Metabolon Inc. Durham, NC, USA). Metabolic datasets comprised a total of 284 and 597 compounds of known identity in BF and plasma, respectively. Diabetes mellitus had profound effects on maternal and embryonic metabolic profiles, with almost half of the metabolites changed. As predicted, we observed an increase in glucose and a decrease in 1,5-anhydroglucitol in diabetic plasma samples. In plasma, fructose, mannose, and sorbitol were elevated in the diabetic group, which may be a way of dealing with excess glucose. In BF, metabolites of the pentose metabolism were especially increased, indicating the need for ribose-based compounds relevant to DNA and RNA metabolism at this very early stage of embryo development. Other changes were more consistent between BF and plasma. Both displayed elevated acylcarnitines, body3-hydroxybutyrate, and multiple compounds within the branched chain amino acid metabolism pathway, suggesting that lipid beta-oxidation is occurring at elevated levels in the diabetic group. This study demonstrates that maternal and embryonic metabolism are closely related. Maternal diabetes mellitus profoundly alters the metabolic profile of the preimplantation embryo with changes in all subclasses of metabolites. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Graphical abstract

29 pages, 5528 KiB  
Article
Estradiol-17β-Induced Changes in the Porcine Endometrial Transcriptome In Vivo
by Piotr Kaczynski, Stefan Bauersachs, Monika Baryla, Ewelina Goryszewska, Jolanta Muszak, Waldemar J. Grzegorzewski and Agnieszka Waclawik
Int. J. Mol. Sci. 2020, 21(3), 890; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21030890 - 30 Jan 2020
Cited by 18 | Viewed by 3985
Abstract
Estradiol-17β (E2) is a key hormone regulating reproductive functions in females. In pigs, E2, as the main conceptus signal, initiates processes resulting in prolonged corpus luteum function, embryo development, and implantation. During early pregnancy the endometrium undergoes morphological and physiological transitions that are [...] Read more.
Estradiol-17β (E2) is a key hormone regulating reproductive functions in females. In pigs, E2, as the main conceptus signal, initiates processes resulting in prolonged corpus luteum function, embryo development, and implantation. During early pregnancy the endometrium undergoes morphological and physiological transitions that are tightly related to transcriptome changes. Recently, however, the importance of E2 as a primary conceptus signal in the pig has been questionable. Thus, the aim of the present study was to determine the effects of E2 on the porcine endometrial transcriptome in vivo and to compare these effects with transcriptome profiles on day 12 of pregnancy. Microarray analysis revealed differentially expressed genes (DEGs) in response to E2 with overrepresented functional terms related to secretive functions, extracellular vesicles, cell adhesion, proliferation and differentiation, tissue rearrangements, immune response, lipid metabolism, and many others. Numerous common DEGs and processes for the endometrium on day 12 of pregnancy and E2-treated endometrium were identified. In summary, the present study is the first evidence for the effect of E2 on transcriptome profiles in porcine endometrium in vivo in the period corresponding to the maternal recognition of pregnancy. The presented results provide a valuable resource for further targeted studies considering genes and pathways regulated by conceptus-derived estrogens and their role in pregnancy establishment. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

14 pages, 1864 KiB  
Article
Vascular Endothelial Growth Factor A and VEGFR-1 Change during Preimplantation in Heifers
by Daniel Chiumia, Anna-Katharina Hankele, Anna E. Groebner, Katy Schulke, Horst-Dieter Reichenbach, Katrin Giller, Valeri Zakhartchenko, Stefan Bauersachs and Susanne E. Ulbrich
Int. J. Mol. Sci. 2020, 21(2), 544; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020544 - 15 Jan 2020
Cited by 9 | Viewed by 2298
Abstract
Vascular endothelial growth factor A (VEGFA) plays a critical angiogenic role in the endometrium of placentalia during preimplantation. The role of VEGFA and its receptors is not fully characterised in bovine reproduction. We analysed the mRNA expression of VEGFA isoforms 121, 165 and [...] Read more.
Vascular endothelial growth factor A (VEGFA) plays a critical angiogenic role in the endometrium of placentalia during preimplantation. The role of VEGFA and its receptors is not fully characterised in bovine reproduction. We analysed the mRNA expression of VEGFA isoforms 121, 165 and 189, and VEGF receptors 1 and 2 in three experimental settings (A, B and C). We compared intercaruncular endometrium of cyclic to pregnant heifers at Days 12, 15 and 18 post insemination (Day 0), and between Day 15 and Day 18 conceptuses (A). We further compared caruncular versus intercaruncular endometrium at Day 15 (B), and endometrium of heifers carrying embryos originating from somatic cell nuclear transfer (SCNT) versus in vitro fertilisation (IVF) at Day 18 (C). Endometrial VEGFA protein was localised and quantified. Pregnant heifers displayed lower intercaruncular endometrial mRNA expression of VEGFA-121 (p = 0.045) and VEGFA-189 (p = 0.009) as well as lower VEGFA protein abundance (p < 0.001) at Day 15. The VEGFA protein was localised in intercaruncular luminal, glandular epithelium and in tunica muscularis of blood vessels. At Day 15, caruncular endometrium displayed higher VEGFA mRNA expression than intercaruncular endometrium (p < 0.05). Intercaruncular endometrial VEGFA protein at Day 18 was higher in abundance in SCNT than in IVF (p = 0.038). Therefore, during preimplantation in cattle, there may be a need for timely physiological reduction in intercaruncular endometrial VEGFA expression in favour of the caruncular area to facilitate a gradient towards the implantation sites. A higher expression of VEGFA in SCNT may predispose for later placentation abnormalities frequently observed following SCNT. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

17 pages, 1900 KiB  
Article
Identification of 56 Proteins Involved in Embryo–Maternal Interactions in the Bovine Oviduct
by Charles Banliat, Guillaume Tsikis, Valérie Labas, Ana-Paula Teixeira-Gomes, Emmanuelle Com, Régis Lavigne, Charles Pineau, Benoit Guyonnet, Pascal Mermillod and Marie Saint-Dizier
Int. J. Mol. Sci. 2020, 21(2), 466; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020466 - 11 Jan 2020
Cited by 15 | Viewed by 3475
Abstract
The bovine embryo develops in contact with the oviductal fluid (OF) during the first 4–5 days of pregnancy. The aim of this study was to decipher the protein interactions occurring between the developing embryo and surrounding OF. In-vitro produced 4–6 cell and morula [...] Read more.
The bovine embryo develops in contact with the oviductal fluid (OF) during the first 4–5 days of pregnancy. The aim of this study was to decipher the protein interactions occurring between the developing embryo and surrounding OF. In-vitro produced 4–6 cell and morula embryos were incubated or not (controls) in post-ovulatory OF (OF-treated embryos) and proteins were then analyzed and quantified by high resolution mass spectrometry (MS) in both embryo groups and in OF. A comparative analysis of MS data allowed the identification and quantification of 56 embryo-interacting proteins originated from the OF, including oviductin (OVGP1) and several annexins (ANXA1, ANXA2, ANXA4) as the most abundant ones. Some embryo-interacting proteins were developmental stage-specific, showing a modulating role of the embryo in protein interactions. Three interacting proteins (OVGP1, ANXA1 and PYGL) were immunolocalized in the perivitelline space and in blastomeres, showing that OF proteins were able to cross the zona pellucida and be taken up by the embryo. Interacting proteins were involved in a wide range of functions, among which metabolism and cellular processes were predominant. This study identified for the first time a high number of oviductal embryo-interacting proteins, paving the way for further targeted studies of proteins potentially involved in the establishment of pregnancy in cattle. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

14 pages, 2245 KiB  
Article
Does Maternal Stress Affect the Early Embryonic Microenvironment? Impact of Long-Term Cortisol Stimulation on the Oviduct Epithelium
by Shuaizhi Du, Nares Trakooljul, Jennifer Schoen and Shuai Chen
Int. J. Mol. Sci. 2020, 21(2), 443; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020443 - 10 Jan 2020
Cited by 8 | Viewed by 3192
Abstract
Maternal stress before or during the sensitive preimplantation phase is associated with reproduction failure. Upon real or perceived threat, glucocorticoids (classic stress hormones) as cortisol are synthesized. The earliest “microenvironment” of the embryo consists of the oviduct epithelium and the oviductal fluid generated [...] Read more.
Maternal stress before or during the sensitive preimplantation phase is associated with reproduction failure. Upon real or perceived threat, glucocorticoids (classic stress hormones) as cortisol are synthesized. The earliest “microenvironment” of the embryo consists of the oviduct epithelium and the oviductal fluid generated via the epithelial barrier. However, to date, the direct effects of cortisol on the oviduct are largely unknown. In the present study, we used a compartmentalized in vitro system to test the hypothesis that a prolonged stimulation with cortisol modifies the physiology of the oviduct epithelium. Porcine oviduct epithelial cells were differentiated at the air–liquid interface and basolaterally stimulated with physiological levels of cortisol representing moderate and severe stress for 21 days. Epithelium structure, transepithelial bioelectric properties, and gene expression were assessed. Furthermore, the distribution and metabolism of cortisol was examined. The polarized oviduct epithelium converted basolateral cortisol to cortisone and thereby reduced the amount of bioactive cortisol reaching the apical compartment. However, extended cortisol stimulation affected its barrier function and the expression of genes involved in hormone signaling and immune response. We conclude that continuing maternal stress with long-term elevated cortisol levels may alter the early embryonic environment by modification of basic oviductal functions. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

17 pages, 2670 KiB  
Article
Maternal Recognition of Pregnancy in the Horse: Are MicroRNAs the Secret Messengers?
by Katrien Smits, Yannick Gansemans, Laurentijn Tilleman, Filip Van Nieuwerburgh, Margot Van De Velde, Ilse Gerits, Cyrillus Ververs, Kim Roels, Jan Govaere, Luc Peelman, Dieter Deforce and Ann Van Soom
Int. J. Mol. Sci. 2020, 21(2), 419; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020419 - 09 Jan 2020
Cited by 10 | Viewed by 4265
Abstract
The signal for maternal recognition of pregnancy (MRP) has still not been identified in the horse. High-throughput molecular biology at the embryo–maternal interface has substantially contributed to the knowledge on pathways affected during MRP, but an integrated study in which proteomics, transcriptomics and [...] Read more.
The signal for maternal recognition of pregnancy (MRP) has still not been identified in the horse. High-throughput molecular biology at the embryo–maternal interface has substantially contributed to the knowledge on pathways affected during MRP, but an integrated study in which proteomics, transcriptomics and miRNA expression can be linked directly is currently lacking. The aim of this study was to provide such analysis. Endometrial biopsies, uterine fluid, embryonic tissues, and yolk sac fluid were collected 13 days after ovulation during pregnant and control cycles from the same mares. Micro-RNA-Sequencing was performed on all collected samples, mRNA-Sequencing on the same tissue samples and mass spectrometry was conducted previously on the same fluid samples. Differential expression of miRNA, mRNA and proteins showed high conformity with literature and confirmed involvement in pregnancy establishment, embryo quality, steroid synthesis and prostaglandin regulation, but the link between differential miRNAs and their targets was limited and did not indicate the identity of an unequivocal signal for MRP in the horse. Differential expression at the embryo–maternal interface was prominent, highlighting a potential role of miRNAs in embryo–maternal communication during early pregnancy in the horse. These data provide a strong basis for future targeted studies. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

17 pages, 2325 KiB  
Article
Metabolomic Profile of Oviductal Extracellular Vesicles across the Estrous Cycle in Cattle
by Julie Gatien, Pascal Mermillod, Guillaume Tsikis, Ophélie Bernardi, Sarah Janati Idrissi, Rustem Uzbekov, Daniel Le Bourhis, Pascal Salvetti, Carmen Almiñana and Marie Saint-Dizier
Int. J. Mol. Sci. 2019, 20(24), 6339; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20246339 - 16 Dec 2019
Cited by 30 | Viewed by 3906
Abstract
Oviductal extracellular vesicles (oEVs) have been proposed as key modulators of gamete/embryo maternal interactions. The aim of this study was to examine the metabolite content of oEVs and its regulation across the estrous cycle in cattle. Oviductal EVs were isolated from bovine oviducts [...] Read more.
Oviductal extracellular vesicles (oEVs) have been proposed as key modulators of gamete/embryo maternal interactions. The aim of this study was to examine the metabolite content of oEVs and its regulation across the estrous cycle in cattle. Oviductal EVs were isolated from bovine oviducts ipsilateral and contralateral to ovulation at four stages of the estrous cycle (post-ovulatory stage, early and late luteal phases, and pre-ovulatory stage). The metabolomic profiling of EVs was performed by proton nuclear magnetic resonance spectroscopy (NMR). NMR identified 22 metabolites in oEVs, among which 15 were quantified. Lactate, myoinositol, and glycine were the most abundant metabolites throughout the estrous cycle. The side relative to ovulation had no effect on the oEVs’ metabolite concentrations. However, levels of glucose-1-phosphate and maltose were greatly affected by the cycle stage, showing up to 100-fold higher levels at the luteal phase than at the peri-ovulatory phases. In contrast, levels of methionine were significantly higher at peri-ovulatory phases than at the late-luteal phase. Quantitative enrichment analyses of oEV-metabolites across the cycle evidenced several significantly regulated metabolic pathways related to sucrose, glucose, and lactose metabolism. This study provides the first metabolomic characterization of oEVs, increasing our understanding of the potential role of oEVs in promoting fertilization and early embryo development. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

16 pages, 3080 KiB  
Article
Expression Profile of the Chromosome 14 MicroRNA Cluster (C14MC) Ortholog in Equine Maternal Circulation throughout Pregnancy and Its Potential Implications
by Pouya Dini, Hossam El-Sheikh Ali, Mariano Carossino, Shavahn C. Loux, A. Esteller-Vico, Kirsten E. Scoggin, Peter Daels and Barry A. Ball
Int. J. Mol. Sci. 2019, 20(24), 6285; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20246285 - 13 Dec 2019
Cited by 13 | Viewed by 3024
Abstract
Equine chromosome 24 microRNA cluster (C24MC), the ortholog of human C14MC, is a pregnancy-related miRNA cluster. This cluster is believed to be implicated in embryonic, fetal, and placental development. The current study aimed to characterize the expression profile of this cluster in maternal [...] Read more.
Equine chromosome 24 microRNA cluster (C24MC), the ortholog of human C14MC, is a pregnancy-related miRNA cluster. This cluster is believed to be implicated in embryonic, fetal, and placental development. The current study aimed to characterize the expression profile of this cluster in maternal circulation throughout equine gestation. The expression profile of miRNAs belonging to this cluster was analyzed in the serum of non-pregnant (diestrus), pregnant (25 d, 45 d, 4 mo, 6 mo, 10 mo), and postpartum mares. Among the miRNAs examined, 11 miRNAs were differentially expressed across the analyzed time-points. Four of these miRNAs (eca-miR-1247-3p, eca-miR-134-5p, eca-miR-382-5p, and eca-miR-433-3p) were found to be enriched in the serum of pregnant mares at Day 25 relative to non-pregnant mares. To further assess the accuracy of these miRNAs in differentiating pregnant (25 d) from non-pregnant mares, receiver operating characteristic (ROC) analysis was performed for each of these miRNAs, revealing that eca-miR-1247-3p and eca-miR-134-5p had the highest accuracy (AUCROC = 0.92 and 0.91, respectively; p < 0.05). Moreover, eca-miR-1247-3p, eca-miR-134-5p, eca-miR-409-3p, and eca-miR-379-5p were enriched in the serum of Day 45 pregnant mares. Among those miRNAs, eca-miR-1247-3p and eca-miR-409-3p retained the highest accuracy as shown by ROC analysis. GO analysis revealed that these miRNAs are mainly implicated in nervous system development as well as organ development. Using in situ hybridization, we localized eca-miR-409-3p in the developing embryo (25 d) and extra-embryonic membranes (25 and 45 d). In conclusion, the present study is the first to elucidate the circulating maternal profile of C24MC-associated miRNAs throughout pregnancy and to suggest that serum eca-miR-1247-3p, eca-miR-134-5p, and eca-miR-409-3p could be used as pregnancy-specific markers during early gestation (25 and 45 d). Overall, the high abundance of these embryo-derived miRNAs in the maternal circulation suggests an embryo-maternal communication during the equine early pregnancy. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

20 pages, 2148 KiB  
Article
Which Low-Abundance Proteins are Present in the Human Milieu of Gamete/Embryo Maternal Interaction?
by Analuce Canha-Gouveia, A. Paradela, António Ramos-Fernández, Maria Teresa Prieto-Sánchez, Maria Luisa Sánchez-Ferrer, Fernando Corrales and Pilar Coy
Int. J. Mol. Sci. 2019, 20(21), 5305; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20215305 - 24 Oct 2019
Cited by 13 | Viewed by 3003
Abstract
The improvement of the embryo culture media is of high relevance due to its influence on successful implantation rates, pregnancy, neonatal outcomes, and potential effects in adult life. The ideal conditions for embryo development are those naturally occurring in the female reproductive tract, [...] Read more.
The improvement of the embryo culture media is of high relevance due to its influence on successful implantation rates, pregnancy, neonatal outcomes, and potential effects in adult life. The ideal conditions for embryo development are those naturally occurring in the female reproductive tract, i.e., the oviductal and uterine fluids. To shed light on the differences between chemical and natural media, we performed the first comparative study of the low abundance proteins in plasma, uterine, and oviductal fluid collected, simultaneously, from healthy and fertile women that underwent a salpingectomy. The rationale for this design derives from the fact that high-abundant proteins in these fluids are usually those coming from blood serum and frequently mask the detection of low abundant proteins with a potentially significant role in specific processes related to the embryo–maternal interaction. The proteomic analysis by 1D-nano LC ESI-MSMS detected several proteins in higher amounts in oviductal fluid when compared to uterine and plasma samples (RL3, GSTA1, EZRI, DPYSL3, GARS, HSP90A). Such oviductal fluid proteins could be a target to improve fertilization rates and early embryo development if used in the culture media. In conclusion, this study presents a high-throughput analysis of female reproductive tract fluids and contributes to the knowledge of oviductal and uterine secretome. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

13 pages, 7846 KiB  
Article
Immunohistochemical Examination of Trophoblast Syncytialization during Early Placentation in Sheep
by Heewon Seo, Fuller W. Bazer, Robert C. Burghardt and Greg A. Johnson
Int. J. Mol. Sci. 2019, 20(18), 4530; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20184530 - 13 Sep 2019
Cited by 39 | Viewed by 4778
Abstract
During the peri-implantation period, multinucleated syncytia are formed in the sheep placenta. For over 20 years the scientific consensus has been that during trophoblast syncytialization in sheep, binucleate trophoblast giant cells (BNCs) differentiate from mononuclear trophoblast cells, and individual BNCs fuse with individual [...] Read more.
During the peri-implantation period, multinucleated syncytia are formed in the sheep placenta. For over 20 years the scientific consensus has been that during trophoblast syncytialization in sheep, binucleate trophoblast giant cells (BNCs) differentiate from mononuclear trophoblast cells, and individual BNCs fuse with individual luminal epithelial (LE) cells to form trinucleate cells. These trophoblast–LE syncytial plaques then grow through continued BNC migration and fusion. Therefore, LE cells are thought to be incorporated into syncytial plaques. However, these ideas were based on electron microscopy studies, without benefit of molecular markers for BNC and LE cells to support conclusions. The aim of this study was to observe interactions between BNCs and uterine LE cells using immunohistochemical localization for molecular markers for BNCs and uterine LE cells. We performed immunofluorescence staining, laser capture microdissection, and TUNEL staining on the uterine–placental tissues of sheep during early placentation. We observed: (1) syncytial cells containing more than two nuclei within the trophoblast cell layer; (2) depolarized LE cells that express caspase 3 and stain positively for TUNEL; (3) engulfment of caspase 3-positive LE cells by trophoblast giant cells (TGCs) and empty spaces within the LE layer at sites of implantation; (4) rapid enlargement of syncytial plaques; and (5) E-cadherin and TUNEL-positive cells within the uterine stroma underlying degenerating LE was coincident with accumulation of CD45-positive cells at these sites. These data suggest that during early placentation: (1) fusion between trophoblasts is not limited to the formation of BNCs, and the term ‘trophoblast giant cell (TGC)’ may be appropriate; (2) LE cells undergo apoptosis; (3) apoptotic LE cells are eliminated by TGCs; (4) fusion is not limited to the incorporation of new BNCs but involves the lateral fusion between growing syncytial plaques; and (5) TGCs carry apoptotic LE cells away from the uterine–placental interface for elimination by immune cells within the stroma. These data indicate that uterine LE cells are not incorporated into syncytial plaques, but are engulfed and eliminated, and that early placentation in sheep is more similar to early placentation in humans than is currently understood in that both develop mononucleated cytotrophoblast and multinucleated syncytiotrophoblast layers of entirely placental origin. The elimination of LE cells by sheep TGCs might provide insights into elimination and penetration of LE cells during human embryo implantation. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

Review

Jump to: Editorial, Research

16 pages, 2153 KiB  
Review
MiRNAs in the Peri-Implantation Period: Contribution to Embryo–Maternal Communication in Pigs
by Monika M. Kaczmarek, Joanna Najmula, Maria M. Guzewska and Emilia Przygrodzka
Int. J. Mol. Sci. 2020, 21(6), 2229; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062229 - 23 Mar 2020
Cited by 30 | Viewed by 3955
Abstract
MicroRNAs (miRNAs) constitute a large family of noncoding RNAs, approximately 22 nucleotides long, which function as guide molecules in RNA silencing. Targeting most protein-coding transcripts, miRNAs are involved in nearly all developmental and pathophysiological processes in animals. To date, the regulatory roles of [...] Read more.
MicroRNAs (miRNAs) constitute a large family of noncoding RNAs, approximately 22 nucleotides long, which function as guide molecules in RNA silencing. Targeting most protein-coding transcripts, miRNAs are involved in nearly all developmental and pathophysiological processes in animals. To date, the regulatory roles of miRNAs in reproduction, such as fertilization, embryo development, implantation, and placenta formation, among others, have been demonstrated in numerous mammalian species, including domestic livestock such as pigs. Over the past years, it appeared that understanding the functions of miRNAs in mammalian reproduction can substantially improve our understanding of the biological challenges of successful reproductive performance. This review describes the current knowledge on miRNAs, specifically in relation to the peri-implantation period when the majority of embryonic mortality occurs in pigs. To present a broader picture of crucial peri-implantation events, we focus on the role of miRNA-processing machinery and miRNA–mRNA infarctions during the maternal recognition of pregnancy, leading to maintenance of the corpus luteum function and further embryo implantation. Furthermore, we summarize the current knowledge on cell-to-cell communication involving extracellular vesicles at the embryo–maternal interface in pigs. Finally, we discuss the potential of circulating miRNAs to serve as indicators of ongoing embryo–maternal crosstalk. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

21 pages, 694 KiB  
Review
Physiologic Events of Embryo Implantation and Decidualization in Human and Non-Human Primates
by Maria Ariadna Ochoa-Bernal and Asgerally T. Fazleabas
Int. J. Mol. Sci. 2020, 21(6), 1973; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21061973 - 13 Mar 2020
Cited by 126 | Viewed by 31364
Abstract
Reproduction is a fundamental process for the preservation of the human species. This process requires a sequence of orchestrated events that are necessary for a successful pregnancy. Two of the most critical steps in the establishment of human pregnancy are implantation and decidualization, [...] Read more.
Reproduction is a fundamental process for the preservation of the human species. This process requires a sequence of orchestrated events that are necessary for a successful pregnancy. Two of the most critical steps in the establishment of human pregnancy are implantation and decidualization, which are required for maternal interactions with the developing embryo. This review primarily highlights the physiological aspects of these two events and the adverse pregnancy outcomes from defective implantation and decidualization. The focus of this review is to provide a general concept of the mechanisms involved during the window of implantation, description of components involved in the process and possible pathologies that could disrupt the embryo implantation and decidualization and specifically as it applies to women and non-human primates. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

20 pages, 2390 KiB  
Review
Promoting Roles of Embryonic Signals in Embryo Implantation and Placentation in Cooperation with Endocrine and Immune Systems
by Hiroshi Fujiwara, Masanori Ono, Yukiyasu Sato, Kazuhiko Imakawa, Takashi Iizuka, Kyosuke Kagami, Tomoko Fujiwara, Akihito Horie, Hirohiko Tani, Akira Hattori, Takiko Daikoku and Yoshihiko Araki
Int. J. Mol. Sci. 2020, 21(5), 1885; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051885 - 10 Mar 2020
Cited by 26 | Viewed by 6393
Abstract
Embryo implantation in the uterus is an essential process for successful pregnancy in mammals. In general, the endocrine system induces sufficient embryo receptivity in the endometrium, where adhesion-promoting molecules increase and adhesion-inhibitory molecules decrease. Although the precise mechanisms remain unknown, it is widely [...] Read more.
Embryo implantation in the uterus is an essential process for successful pregnancy in mammals. In general, the endocrine system induces sufficient embryo receptivity in the endometrium, where adhesion-promoting molecules increase and adhesion-inhibitory molecules decrease. Although the precise mechanisms remain unknown, it is widely accepted that maternal–embryo communications, including embryonic signals, improve the receptive ability of the sex steroid hormone-primed endometrium. The embryo may utilize repulsive forces produced by an Eph–ephrin system for its timely attachment to and subsequent invasion through the endometrial epithelial layer. Importantly, the embryonic signals are considered to act on maternal immune cells to induce immune tolerance. They also elicit local inflammation that promotes endometrial differentiation and maternal tissue remodeling during embryo implantation and placentation. Additional clarification of the immune control mechanisms by embryonic signals, such as human chorionic gonadotropin, pre-implantation factor, zona pellucida degradation products, and laeverin, will aid in the further development of immunotherapy to minimize implantation failure in the future. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

38 pages, 4357 KiB  
Review
Persistent Breeding-Induced Endometritis in Mares—A Multifaceted Challenge: From Clinical Aspects to Immunopathogenesis and Pathobiology
by Igor F. Canisso, Lorenzo G.T.M. Segabinazzi and Carleigh E. Fedorka
Int. J. Mol. Sci. 2020, 21(4), 1432; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041432 - 20 Feb 2020
Cited by 76 | Viewed by 13760
Abstract
Post-breeding endometritis (i.e., inflammation/infection of the endometrium), is a physiological reaction taking place in the endometrium of mares within 48 h post-breeding, aimed to clear seminal plasma, excess sperm, microorganisms, and debris from the uterine lumen in preparation for the arrival of an [...] Read more.
Post-breeding endometritis (i.e., inflammation/infection of the endometrium), is a physiological reaction taking place in the endometrium of mares within 48 h post-breeding, aimed to clear seminal plasma, excess sperm, microorganisms, and debris from the uterine lumen in preparation for the arrival of an embryo. Mares are classified as susceptible or resistant to persistent breeding-induced endometritis (PBIE) based on their ability to clear this inflammation/infection by 48 h post-breeding. Mares susceptible to PBIE, or those with difficulty clearing infection/inflammation, have a deficient immune response and compromised physical mechanisms of defense against infection. Molecular pathways of the innate immune response known to be involved in PBIE are discussed herein. The role of the adaptive uterine immune response on PBIE remains to be elucidated in horses. Advances in the pathobiology of microbes involved in PBIE are also revised here. Traditional and non-traditional therapeutic modalities for endometritis are contrasted and described in the context of clinical and molecular aspects. In recent years, the lack of efficacy of traditional therapeutic modalities, alongside the ever-increasing incidence of antibiotic-resistant microorganisms, has enforced the development of non-traditional therapies. Novel biological products capable of modulating the endometrial inflammatory response are also discussed here as part of the non-traditional therapies for endometritis. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

15 pages, 499 KiB  
Review
Extracellular Vesicles Mediated Early Embryo–Maternal Interactions
by Alessandra Bridi, Felipe Perecin and Juliano Coelho da Silveira
Int. J. Mol. Sci. 2020, 21(3), 1163; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21031163 - 10 Feb 2020
Cited by 48 | Viewed by 6339
Abstract
Embryo–maternal crosstalk is an important event that involves many biological processes, which must occur perfectly for pregnancy success. This complex communication starts from the zygote stage within the oviduct and continues in the uterus up to the end of pregnancy. Small extracellular vesicles [...] Read more.
Embryo–maternal crosstalk is an important event that involves many biological processes, which must occur perfectly for pregnancy success. This complex communication starts from the zygote stage within the oviduct and continues in the uterus up to the end of pregnancy. Small extracellular vesicles (EVs) are part of this communication and carry bioactive molecules such as proteins, lipids, mRNA, and miRNA. Small EVs are present in the oviductal and uterine fluid and have important functions during fertilization and early embryonic development. Embryonic cells are able to uptake oviductal and endometrium-derived small EVs. Conversely, embryo-derived EVs might modulate oviductal and uterine function. In this review, our aim is to demonstrate the role of extracellular vesicles modulating embryo–maternal interactions during early pregnancy. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

20 pages, 783 KiB  
Review
The Role of MicroRNAs in Mammalian Fertility: From Gametogenesis to Embryo Implantation
by Dessie Salilew-Wondim, Samuel Gebremedhn, Michael Hoelker, Ernst Tholen, Tsige Hailay and Dawit Tesfaye
Int. J. Mol. Sci. 2020, 21(2), 585; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020585 - 16 Jan 2020
Cited by 40 | Viewed by 5510
Abstract
The genetic codes inscribed during two key developmental processes, namely gametogenesis and embryogenesis, are believed to determine subsequent development and survival of adult life. Once the embryo is formed, its further development mainly depends on its intrinsic characteristics, maternal environment (the endometrial receptivity), [...] Read more.
The genetic codes inscribed during two key developmental processes, namely gametogenesis and embryogenesis, are believed to determine subsequent development and survival of adult life. Once the embryo is formed, its further development mainly depends on its intrinsic characteristics, maternal environment (the endometrial receptivity), and the embryo–maternal interactions established during each phase of development. These developmental processes are under strict genetic regulation that could be manifested temporally and spatially depending on the physiological and developmental status of the cell. MicroRNAs (miRNAs), one of the small non-coding classes of RNAs, approximately 19–22 nucleotides in length, are one of the candidates for post-transcriptional developmental regulators. These tiny non-coding RNAs are expressed in ovarian tissue, granulosa cells, testis, oocytes, follicular fluid, and embryos and are implicated in diverse biological processes such as cell-to-cell communication. Moreover, accumulated evidences have also highlighted that miRNAs can be released into the extracellular environment through different mechanisms facilitating intercellular communication. Therefore, understanding miRNAs mediated regulatory mechanisms during gametogenesis and embryogenesis provides further insights about the molecular mechanisms underlying oocyte/sperm formation, early embryo development, and implantation. Thus, this review highlights the role of miRNAs in mammalian gametogenesis and embryogenesis and summarizes recent findings about miRNA-mediated post-transcriptional regulatory mechanisms occurring during early mammalian development. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

21 pages, 4282 KiB  
Review
Composing the Early Embryonic Microenvironment: Physiology and Regulation of Oviductal Secretions
by Marie Saint-Dizier, Jennifer Schoen, Shuai Chen, Charles Banliat and Pascal Mermillod
Int. J. Mol. Sci. 2020, 21(1), 223; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21010223 - 28 Dec 2019
Cited by 59 | Viewed by 7932
Abstract
The oviductal fluid is the first environment experienced by mammalian embryos at the very beginning of life. However, it has long been believed that the oviductal environment was not essential for proper embryonic development. Successful establishment of in vitro embryo production techniques (which [...] Read more.
The oviductal fluid is the first environment experienced by mammalian embryos at the very beginning of life. However, it has long been believed that the oviductal environment was not essential for proper embryonic development. Successful establishment of in vitro embryo production techniques (which completely bypass the oviduct) have reinforced this idea. Yet, it became evident that in vitro produced embryos differ markedly from their in vivo counterparts, and these differences are associated with lower pregnancy outcomes and more health issues after birth. Nowadays, researchers consider the oviduct as the most suitable microenvironment for early embryonic development and a substantial effort is made to understand its dynamic, species-specific functions. In this review, we touch on the origin and molecular components of the oviductal fluid in mammals, where recent progress has been made thanks to the wider use of mass spectrometry techniques. Some of the factors and processes known to regulate oviductal secretions, including the embryo itself, as well as ovulation, insemination, endogenous and exogenous hormones, and metabolic and heat stress, are summarized. Special emphasis is laid on farm animals because, owing to the availability of sample material and the economic importance of fertility in livestock husbandry, a large part of the work on this topic has been carried out in domestic animals used for dairy and/or meat production. Full article
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-24
Back to TopTop