Biomolecules in Parental–Embryo Communication and Implantation

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Reproduction".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 21004

Special Issue Editors


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Guest Editor
Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield S10 2SF, UK
Interests: maternal communication with gametes and embryos; sperm function; cryobiology; conservation biology
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Physiology, International Excellence Campus for Higher Education and Research “Campus Mare Nostrum” and Institute for Biomedical Research of Murcia (IMIB-Arrixaca), University of Murcia, 30100 Murcia, Spain
Interests: animal reproduction; fertility; sperm assestment; gene editing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The planned Special Issue in Biomolecules will be dedicated to parent–offspring communication in relation to reproduction, fertilization and embryonic development in mammals and other vertebrates. As is widely recognized, parental effects mediated via the environment can influence the future health of the next generation, stemming from both the preconception period as well as early pregnancy. In fact, environmental effects have crucially important influences on the achievement of reproductive success in all mammalian species, including humans, as well as some of the lower vertebrates. Long-range and short-range signaling biomolecules play important roles in mediating cell–cell communications between parents and embryos. Slight malfunctions or disturbances of the environment that host these interactions can retard embryonic development and may result in infertility, inadequate development, pregnancy loss or pregnancy complications. Despite an overwhelming amount of research, not all signaling biomolecules and mechanisms involved and their relationship with each other are known at the early stages of conception. This Special Issue of the journal Biomolecules assembles review and research papers, focusing on different approaches aiming to improve our understanding of biomolecules involved in embryonic development prior to implantation, endometrial receptivity required for implantation, and the various molecular parent–embryo interactions occurring in early stages of gestation. This fundamental and translational novel knowledge allows us to better understand reproductive processes and to better deal with challenges in reproductive medicine, adverse environments and biotechnological challenges.

Prof. Dr. Bill Holt
Prof. Dr. Joaquín Gadea
Guest Editors

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Keywords

  • parental–embryo communication
  • preimplantation embryo
  • endometrial receptivity
  • embryo implantation
  • sperm storage in vivo
  • sperm transport

Published Papers (9 papers)

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Editorial

Jump to: Research, Review

3 pages, 197 KiB  
Editorial
Information Flow between Parents and Offspring Is Essential for Successful Development
by William V. Holt and Joaquin Gadea
Biomolecules 2023, 13(9), 1299; https://0-doi-org.brum.beds.ac.uk/10.3390/biom13091299 - 24 Aug 2023
Cited by 1 | Viewed by 551
Abstract
Over the last several decades, the sciences of developmental biology and physiology have expanded and intertwined their scope enormously [...] Full article
(This article belongs to the Special Issue Biomolecules in Parental–Embryo Communication and Implantation)

Research

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22 pages, 3854 KiB  
Article
The Extracellular Vesicles Proteome of Endometrial Cells Simulating the Receptive Menstrual Phase Differs from That of Endometrial Cells Simulating the Non-Receptive Menstrual Phase
by Amber Rose Hart, Norhayati Liaqat Ali Khan, Keerthie Dissanayake, Kasun Godakumara, Aneta Andronowska, Saji Eapen, Paul R Heath and Alireza Fazeli
Biomolecules 2023, 13(2), 279; https://0-doi-org.brum.beds.ac.uk/10.3390/biom13020279 - 02 Feb 2023
Cited by 6 | Viewed by 2321
Abstract
Successful embryo implantation into a receptive endometrium requires mutual endometrial-embryo communication. Recently, the function of extracellular vehicles (EVs) in cell-to-cell interaction in embryo-maternal interactions has been investigated. We explored isolated endometrial-derived EVs, using RL95-2 cells as a model of a receptive endometrium, influenced [...] Read more.
Successful embryo implantation into a receptive endometrium requires mutual endometrial-embryo communication. Recently, the function of extracellular vehicles (EVs) in cell-to-cell interaction in embryo-maternal interactions has been investigated. We explored isolated endometrial-derived EVs, using RL95-2 cells as a model of a receptive endometrium, influenced by the menstrual cycle hormones estrogen (E2; proliferative phase), progesterone (P4; secretory phase), and estrogen plus progesterone (E2P4; the receptive phase). EV sized particles were isolated by differential centrifugation and size exclusion chromatography. Nanoparticle tracking analysis was used to examine the different concentrations and sizes of particles and EV proteomic analysis was performed using shotgun label-free mass spectrometry. Our results showed that although endometrial derived EVs were secreted in numbers independent of hormonal stimulation, EV sizes were statistically modified by it. Proteomics analysis showed that hormone treatment changes affect the endometrial EV’s proteome, with proteins enhanced within the EV E2P4 group shown to be involved in different processes, such as embryo implantation, endometrial receptivity, and embryo development, supporting the concept of a communication system between the embryo and the maternal endometrium via EVs. Full article
(This article belongs to the Special Issue Biomolecules in Parental–Embryo Communication and Implantation)
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24 pages, 2979 KiB  
Article
Oviductal Extracellular Vesicles Enhance Porcine In Vitro Embryo Development by Modulating the Embryonic Transcriptome
by Agostinho Soares de Alcântara-Neto, Cristina Cuello, Rustem Uzbekov, Stefan Bauersachs, Pascal Mermillod and Carmen Almiñana
Biomolecules 2022, 12(9), 1300; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12091300 - 15 Sep 2022
Cited by 8 | Viewed by 2259
Abstract
Oviductal extracellular vesicles (oEVs) have been identified as important components of the oviductal fluid (OF) and have been pointed to as key modulators of gamete/embryo-maternal interactions. Here, we determined the functional impact of oEVs on embryo development and the embryonic transcriptome in porcine. [...] Read more.
Oviductal extracellular vesicles (oEVs) have been identified as important components of the oviductal fluid (OF) and have been pointed to as key modulators of gamete/embryo-maternal interactions. Here, we determined the functional impact of oEVs on embryo development and the embryonic transcriptome in porcine. Experiment 1 examined the effect of oEVs and OF on embryo development. In vitro-produced embryos were cultured with oEVs or OF for 2 or 7 days using an in vitro sequential system or without supplementation (control). Experiment 2 analyzed transcriptomic alterations of EV-treated embryos versus control and the oEVs RNA cargo by RNA-sequencing. Two days of EV treatment enhanced embryo development over time when compared to other treatments. Different RNA expression profiles between embryos treated with EVs for two or seven days and untreated controls were obtained, with 54 and 59 differentially expressed (DE) genes and six and seven DE miRNAs, respectively. In oEV RNA cargo, 12,998 RNAs and 163 miRNAs were identified. Integrative analyses pointed to specific oEV components that might act as modulators of the embryonic transcriptome, such as S100A11, ANXA2 or miR-21-5p. Overall, the findings suggested that oEVs could be a potential strategy to improve porcine IVP outcomes, particularly by using two days of EV treatment. Full article
(This article belongs to the Special Issue Biomolecules in Parental–Embryo Communication and Implantation)
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11 pages, 1719 KiB  
Article
Maternal Chronic Ethanol Exposure Decreases Stress Responses in Zebrafish Offspring
by Juliet E. Kitson, James Ord and Penelope J. Watt
Biomolecules 2022, 12(8), 1143; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12081143 - 19 Aug 2022
Cited by 1 | Viewed by 1667
Abstract
In humans, prenatal alcohol exposure can cause serious health issues in children, known collectively as Foetal Alcohol Spectrum Disorders (FASD). Despite the high prevalence of FASD and a lack of effective treatments, the underlying mechanisms causing the teratogenic action of ethanol are still [...] Read more.
In humans, prenatal alcohol exposure can cause serious health issues in children, known collectively as Foetal Alcohol Spectrum Disorders (FASD). Despite the high prevalence of FASD and a lack of effective treatments, the underlying mechanisms causing the teratogenic action of ethanol are still obscure. The limitations of human studies necessitate the use of animal models for identifying the underlying processes, but few studies have investigated the effects of alcohol in the female germline. Here, we used the zebrafish Danio rerio to investigate the effects of chronic (repeated for seven days) exposure to alcohol. Specifically, we tested whether the offspring of females chronically exposed to ethanol during oogenesis exhibited hormonal abnormalities when subjected to a stressor (alarm cue) as larvae, and if they exhibited anxiety-like behaviours as adults. Exposure to alarm cue increased whole-body cortisol in control larvae but not in those of ethanol-treated females. Furthermore, adult offspring of ethanol-treated females showed some reduced anxiety-like behaviours. These findings suggest that the offspring of ethanol-treated females had reduced stress responses. This study is the first to investigate how maternal chronic ethanol exposure prior to fertilisation influences hormonal and behavioural effects in a non-rodent model. Full article
(This article belongs to the Special Issue Biomolecules in Parental–Embryo Communication and Implantation)
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11 pages, 3812 KiB  
Article
Cortisol Regulates Cerebral Mitochondrial Oxidative Phosphorylation and Morphology of the Brain in a Region-Specific Manner in the Ovine Fetus
by Katie L. Davies, Danielle J. Smith, Tatiana El-Bacha, Peter F. P. Wooding, Alison J. Forhead, Andrew J. Murray, Abigail L. Fowden and Emily J. Camm
Biomolecules 2022, 12(6), 768; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12060768 - 31 May 2022
Cited by 1 | Viewed by 2050
Abstract
In adults, glucocorticoids are stress hormones that act, partly, through actions on mitochondrial oxidative phosphorylation (OXPHOS) to increase energy availability. Before birth, glucocorticoids are primarily maturational signals that prepare the fetus for new postnatal challenges. However, the role of the normal prepartum glucocorticoid [...] Read more.
In adults, glucocorticoids are stress hormones that act, partly, through actions on mitochondrial oxidative phosphorylation (OXPHOS) to increase energy availability. Before birth, glucocorticoids are primarily maturational signals that prepare the fetus for new postnatal challenges. However, the role of the normal prepartum glucocorticoid rise in preparing mitochondria for the increased postnatal energy demands remains largely unknown. This study examined the effect of physiological increases in the fetal cortisol concentration on cerebral mitochondrial OXPHOS capacity near term (~130 days gestation, term ~145 days gestation). Fetal sheep were infused with saline or cortisol for 5 days at ~0.8 of gestation before the mitochondrial content, respiratory rates, abundance of the electron transfer system proteins and OXPHOS efficiency were measured in their cortex and cerebellum. Cerebral morphology was assessed by immunohistochemistry and stereology. Cortisol treatment increased the mitochondrial content, while decreasing Complex I-linked respiration in the cerebellum. There was no effect on the cortical mitochondrial OXPHOS capacity. Cortisol infusion had regional effects on cerebral morphology, with increased myelination in the cerebrum. The findings demonstrate the importance of cortisol in regulating the cerebral mitochondrial OXPHOS capacity prenatally and have implications for infants born preterm or after glucocorticoid overexposure due to pregnancy complications or clinical treatment. Full article
(This article belongs to the Special Issue Biomolecules in Parental–Embryo Communication and Implantation)
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Review

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20 pages, 1555 KiB  
Review
Towards a Better Understanding of Endometriosis-Related Infertility: A Review on How Endometriosis Affects Endometrial Receptivity
by Jing Shan, Da-Jin Li and Xiao-Qiu Wang
Biomolecules 2023, 13(3), 430; https://0-doi-org.brum.beds.ac.uk/10.3390/biom13030430 - 24 Feb 2023
Cited by 6 | Viewed by 3943
Abstract
Endometriosis is the most common cause of infertility. Endometrial receptivity has been suggested to contribute to infertility and poor reproductive outcomes in affected women. Even though experimental and clinical data suggest that the endometrium differs in women with endometriosis, the pathogenesis of impaired [...] Read more.
Endometriosis is the most common cause of infertility. Endometrial receptivity has been suggested to contribute to infertility and poor reproductive outcomes in affected women. Even though experimental and clinical data suggest that the endometrium differs in women with endometriosis, the pathogenesis of impaired endometrial receptivity remains incomplete. Therefore, this review summarizes the potential mechanisms that affect endometrial function and contribute to implantation failure. Contemporary data regarding hormone imbalance, inflammation, and immunoregulatory dysfunction will be reviewed here. In addition, genetic, epigenetic, glycosylation, metabolism and microRNA in endometriosis-related infertility/subfertility will be summarized. We provide a brief discussion and perspectives on their future clinical implications in the diagnosis and therapy to improve endometrial function in affected women. Full article
(This article belongs to the Special Issue Biomolecules in Parental–Embryo Communication and Implantation)
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15 pages, 806 KiB  
Review
Distinguishing Between Embryonic Provisioning Strategies in Teleost Fishes Using a Threshold Value for Parentotrophy
by Zoe M. G. Skalkos, James U. Van Dyke and Camilla M. Whittington
Biomolecules 2023, 13(1), 166; https://0-doi-org.brum.beds.ac.uk/10.3390/biom13010166 - 13 Jan 2023
Cited by 5 | Viewed by 1732
Abstract
The source of embryonic nutrition for development varies across teleost fishes. A parentotrophy index (ratio of neonate: ovulated egg dry mass) is often used to determine provisioning strategy, but the methodologies used vary across studies. The variation in source and preservation of tissue, [...] Read more.
The source of embryonic nutrition for development varies across teleost fishes. A parentotrophy index (ratio of neonate: ovulated egg dry mass) is often used to determine provisioning strategy, but the methodologies used vary across studies. The variation in source and preservation of tissue, staging of embryos, and estimation approach impedes our ability to discern between methodological and biological differences in parentotrophy indices inter- and intra-specifically. The threshold value used to distinguish between lecithotrophy and parentotrophy (0.6–1) differs considerably across studies. The lack of a standardised approach in definition and application of parentotrophy indices has contributed to inconsistent classifications of provisioning strategy. Consistency in both methodology used to obtain a parentotrophy index, and in the classification of provisioning strategy using a threshold value are essential to reliably distinguish between provisioning strategies in teleosts. We discuss alternative methods for determining parentotrophy and suggest consistent standards for obtaining and interpreting parentotrophy indices. Full article
(This article belongs to the Special Issue Biomolecules in Parental–Embryo Communication and Implantation)
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18 pages, 831 KiB  
Review
Conservation Biology and Reproduction in a Time of Developmental Plasticity
by William V. Holt and Pierre Comizzoli
Biomolecules 2022, 12(9), 1297; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12091297 - 14 Sep 2022
Cited by 3 | Viewed by 2030
Abstract
The objective of this review is to ask whether, and how, principles in conservation biology may need to be revisited in light of new knowledge about the power of epigenetics to alter developmental pathways. Importantly, conservation breeding programmes, used widely by zoological parks [...] Read more.
The objective of this review is to ask whether, and how, principles in conservation biology may need to be revisited in light of new knowledge about the power of epigenetics to alter developmental pathways. Importantly, conservation breeding programmes, used widely by zoological parks and aquariums, may appear in some cases to reduce fitness by decreasing animals’ abilities to cope when confronted with the ‘wild side’ of their natural habitats. Would less comfortable captive conditions lead to the selection of individuals that, despite being adapted to life in a captive environment, be better able to thrive if relocated to a more natural environment? While threatened populations may benefit from advanced reproductive technologies, these may actually induce undesirable epigenetic changes. Thus, there may be inherent risks to the health and welfare of offspring (as is suspected in humans). Advanced breeding technologies, especially those that aim to regenerate the rarest species using stem cell reprogramming and artificial gametes, may also lead to unwanted epigenetic modifications. Current knowledge is still incomplete, and therefore ethical decisions about novel breeding methods remain controversial and difficult to resolve. Full article
(This article belongs to the Special Issue Biomolecules in Parental–Embryo Communication and Implantation)
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16 pages, 730 KiB  
Review
Parental Programming of Offspring Health: The Intricate Interplay between Diet, Environment, Reproduction and Development
by Vipul Batra, Emily Norman, Hannah L. Morgan and Adam J. Watkins
Biomolecules 2022, 12(9), 1289; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12091289 - 13 Sep 2022
Cited by 8 | Viewed by 3651
Abstract
As adults, our health can be influenced by a range of lifestyle and environmental factors, increasing the risk for developing a series of non-communicable diseases such as type 2 diabetes, heart disease and obesity. Over the past few decades, our understanding of how [...] Read more.
As adults, our health can be influenced by a range of lifestyle and environmental factors, increasing the risk for developing a series of non-communicable diseases such as type 2 diabetes, heart disease and obesity. Over the past few decades, our understanding of how our adult health can be shaped by events occurring before birth has developed into a well-supported concept, the Developmental Origins of Health and Disease (DOHaD). Supported by epidemiological data and experimental studies, specific mechanisms have been defined linking environmental perturbations, disrupted fetal and neonatal development and adult ill-health. Originally, such studies focused on the significance of poor maternal health during pregnancy. However, the role of the father in directing the development and well-being of his offspring has come into recent focus. Whereas these studies identify the individual role of each parent in shaping the long-term health of their offspring, few studies have explored the combined influences of both parents on offspring well-being. Such understanding is necessary as parental influences on offspring development extend beyond the direct genetic contributions from the sperm and oocyte. This article reviews our current understanding of the parental contribution to offspring health, exploring some of the mechanisms linking parental well-being with gamete quality, embryo development and offspring health. Full article
(This article belongs to the Special Issue Biomolecules in Parental–Embryo Communication and Implantation)
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