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Development and Function of the Reproductive System

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

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 21245

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Special Issue Editor

Dr. Emanuele Pelosi

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Guest Editor

Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia
Interests: differences/disorders of sex development; mullerian anomalies; reproduction; reproductive medicine; genetics; ovary; fertility; developmental biology; CRISPR

Special Issue Information

Dear Colleagues,

I invite you to contribute to the Special Issue on Development and Function of the Reproductive System for the International Journal of Molecular Sciences.

The development of the reproductive system is a finely regulated and highly complex process. It involves the formation of testes or ovaries from bipotential, undifferentiated gonads, and the development of a specialized reproductive tract. Since the groundbreaking discovery of the testis-determining gene Sry thirty years ago, significant progress has been made in understanding the molecular and cellular mechanisms driving sex development and regulating reproductive functions. Nonetheless, the role and even identity of several factors and pathways involved in cell fate decisions, survival, and differentiation remain unclear.

Impairment of these dimorphic developmental programs may lead to differences/disorders of sex development (DSD) and have dramatic consequences on fertility and reproductive health. Defining the role of gene networks and factors, including environmental factors, on gonadal and reproductive tract differentiation is critical to improving the diagnosis and management of DSD and other reproductive conditions. New genomic and translational approaches hold enormous potential to solve these issues and uncover unknown mechanisms regulating development and function of the reproductive system.

In this Special Issue, I invite contributions in the form of original research articles and reviews articles on all aspects related to reproductive development and function.

Dr. Emanuele Pelosi
Guest Editor

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

differences/disorders of sex development
mullerian anomalies
reproductive tract
sex determination
bipotential gonads
ovary
testis
reproduction
fertility
developmental biology
congenital conditions
mouse models

Published Papers (7 papers)

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Research

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20 pages, 6866 KiB

Open AccessArticle

Role of EZH2 in Uterine Gland Development

by Nan Ni, Frank L. Jalufka, Xin Fang, Dylan A. McCreedy and Qinglei Li

Int. J. Mol. Sci. 2022, 23(24), 15665; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232415665 - 10 Dec 2022

Cited by 4 | Viewed by 1631

Abstract

Enhancer of zeste homolog 2 (EZH2) is a core component of polycomb repressive complex 2 that plays a vital role in transcriptional repression of gene expression. Conditional ablation of EZH2 using progesterone receptor (Pgr)-Cre in the mouse uterus has uncovered its roles in regulating uterine epithelial cell growth and stratification, suppressing decidual myofibroblast activation, and maintaining normal female fertility. However, it is unclear whether EZH2 plays a role in the development of uterine glands, which are required for pregnancy success. Herein, we created mice with conditional deletion of Ezh2 using anti-Mullerian hormone receptor type 2 (Amhr2)-Cre recombinase that is expressed in mesenchyme-derived cells of the female reproductive tract. Strikingly, these mice showed marked defects in uterine adenogenesis. Unlike Ezh2 Pgr-Cre conditional knockout mice, deletion of Ezh2 using Amhr2-Cre did not lead to the differentiation of basal-like cells in the uterus. The deficient uterine adenogenesis was accompanied by impaired uterine function and pregnancy loss. Transcriptomic profiling using next generation sequencing revealed dysregulation of genes associated with signaling pathways that play fundamental roles in development and disease. In summary, this study has identified an unrecognized role of EZH2 in uterine gland development, a postnatal event critical for pregnancy success and female fertility. Full article

(This article belongs to the Special Issue Development and Function of the Reproductive System)

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17 pages, 6647 KiB

Open AccessArticle

Loss of Runx1 Induces Granulosa Cell Defects and Development of Ovarian Tumors in the Mouse

by Kamiya Bridges, Humphrey H.-C. Yao and Barbara Nicol

Int. J. Mol. Sci. 2022, 23(22), 14442; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232214442 - 21 Nov 2022

Cited by 2 | Viewed by 2279

Abstract

Genetic alterations of the RUNX1 gene are associated with a variety of malignancies, including female-related cancers. The role of RUNX1 as either a tumor suppressor gene or an oncogene is tissue-dependent and varies based on the cancer type. Both the amplification and deletion of the RUNX1 gene have been associated with ovarian cancer in humans. In this study, we investigated the effects of Runx1 loss on ovarian pathogenesis in mice. A conditional loss of Runx1 in the somatic cells of the ovary led to an increased prevalence of ovarian tumors in aged mice. By the age of 15 months, 27% of Runx1 knockout (KO) females developed ovarian tumors that presented characteristics of granulosa cell tumors. While ovaries from young adult mice did not display tumors, they all contained abnormal follicle-like lesions. The granulosa cells composing these follicle-like lesions were quiescent, displayed defects in differentiation and were organized in a rosette-like pattern. The RNA-sequencing analysis further revealed differentially expressed genes in Runx1 KO ovaries, including genes involved in metaplasia, ovarian cancer, epithelial cell development, tight junctions, cell−cell adhesion, and the Wnt/beta-catenin pathway. Together, this study showed that Runx1 is required for normal granulosa cell differentiation and prevention of ovarian tumor development in mice. Full article

(This article belongs to the Special Issue Development and Function of the Reproductive System)

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18 pages, 4191 KiB

Open AccessArticle

Analysis of Ser/Thr Kinase HASPIN-Interacting Proteins in the Spermatids

by Naoko Maeda, Junji Tsuchida, Yoshitake Nishimune and Hiromitsu Tanaka

Int. J. Mol. Sci. 2022, 23(16), 9060; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23169060 - 13 Aug 2022

Cited by 1 | Viewed by 1603

Abstract

HASPIN is predominantly expressed in spermatids, and plays an important role in cell division in somatic and meiotic cells through histone H3 phosphorylation. The literature published to date has suggested that HASPIN may play multiple roles in cells. Here, 10 gene products from the mouse testis cDNA library that interact with HASPIN were isolated using the two-hybrid system. Among them, CENPJ/CPAP, KPNA6/importin alpha 6, and C1QBP/HABP1 were analyzed in detail for their interactions with HASPIN, with HASPIN phosphorylated C1QBP as the substrate. The results indicated that HASPIN is involved in spermatogenesis through the phosphorylation of C1QBP in spermatids, and also may be involved in the formation of centrosomes. Full article

(This article belongs to the Special Issue Development and Function of the Reproductive System)

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Review

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18 pages, 2256 KiB

Open AccessReview

Deciphering the Roles & Regulation of Estradiol Signaling during Female Mini-Puberty: Insights from Mouse Models

by Marie M. Devillers, Sakina Mhaouty-Kodja and Céline J. Guigon

Int. J. Mol. Sci. 2022, 23(22), 13695; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232213695 - 08 Nov 2022

Cited by 6 | Viewed by 4584

Abstract

Mini-puberty of infancy is a short developmental phase occurring in humans and other mammals after birth. In females, it corresponds to transient and robust activation of the hypothalamo-pituitary-ovarian (HPO) axis revealed by high levels of gonadotropin hormones, follicular growth, and increased estradiol production by the ovary. The roles of estradiol signaling during this intriguing developmental phase are not yet well known, but accumulating data support the idea that it aids in the implementation of reproductive function. This review aims to provide in-depth information on HPO activity during this particular developmental phase in several mammal species, including humans, and to propose emerging hypotheses on the putative effect of estradiol signaling on the development and function of organs involved in female reproduction. Full article

(This article belongs to the Special Issue Development and Function of the Reproductive System)

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19 pages, 1905 KiB

Open AccessReview

Gonadal Sex Differentiation and Ovarian Organogenesis along the Cortical–Medullary Axis in Mammals

by Kenya Imaimatsu, Aya Uchida, Ryuji Hiramatsu and Yoshiakira Kanai

Int. J. Mol. Sci. 2022, 23(21), 13373; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113373 - 02 Nov 2022

Cited by 2 | Viewed by 4844

Abstract

In most mammals, the sex of the gonads is based on the fate of the supporting cell lineages, which arises from the proliferation of coelomic epithelium (CE) that surfaces on the bipotential genital ridge in both XY and XX embryos. Recent genetic studies and single-cell transcriptome analyses in mice have revealed the cellular and molecular events in the two-wave proliferation of the CE that produce the supporting cells. This proliferation contributes to the formation of the primary sex cords in the medullary region of both the testis and the ovary at the early phase of gonadal sex differentiation, as well as to that of the secondary sex cords in the cortical region of the ovary at the perinatal stage. To support gametogenesis, the testis forms seminiferous tubules in the medullary region, whereas the ovary forms follicles mainly in the cortical region. The medullary region in the ovary exhibits morphological and functional diversity among mammalian species that ranges from ovary-like to testis-like characteristics. This review focuses on the mechanism of gonadal sex differentiation along the cortical-medullary axis and compares the features of the cortical and medullary regions of the ovary in mammalian species. Full article

(This article belongs to the Special Issue Development and Function of the Reproductive System)

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19 pages, 1151 KiB

Open AccessReview

Molecular Clues to Understanding Causes of Human-Assisted Reproduction Treatment Failures and Possible Treatment Options

by Jan Tesarik and Raquel Mendoza-Tesarik

Int. J. Mol. Sci. 2022, 23(18), 10357; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231810357 - 08 Sep 2022

Viewed by 2383

Abstract

More than forty years after the first birth following in vitro fertilization (IVF), the success rates of IVF and of IVF-derived assisted reproduction techniques (ART) still remain relatively low. Interindividual differences between infertile couples and the nature of the problems underlying their infertility appear to be underestimated nowadays. Consequently, the molecular basis of each couple’s reproductive function and of its disturbances is needed to offer an individualized diagnostic and therapeutic approaches to each couple, instead of applying a standard or minimally adapted protocols to everybody. Interindividual differences include sperm and oocyte function and health status, early (preimplantation) embryonic development, the optimal window of uterine receptivity for the implanting embryo, the function of the corpus luteum as the main source of progesterone production during the first days of pregnancy, the timing of the subsequent luteoplacental shift in progesterone production, and aberrant reactions of the uterine immune cells to the implanting and recently implanted embryos. In this article, the molecular basis that underlies each of these abnormalities is reviewed and discussed, with the aim to design specific treatment options to be used for each of them. Full article

(This article belongs to the Special Issue Development and Function of the Reproductive System)

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24 pages, 1357 KiB

Open AccessReview

LIN28 Family in Testis: Control of Cell Renewal, Maturation, Fertility and Aging

by Dajana Krsnik, Tihana Marić, Floriana Bulić-Jakuš, Nino Sinčić and Ana Katušić Bojanac

Int. J. Mol. Sci. 2022, 23(13), 7245; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23137245 - 29 Jun 2022

Cited by 4 | Viewed by 2749

Abstract

Male reproductive development starts early in the embryogenesis with somatic and germ cell differentiation in the testis. The LIN28 family of RNA-binding proteins promoting pluripotency has two members—LIN28A and LIN28B. Their function in the testis has been investigated but many questions about their exact role based on the expression patterns remain unclear. LIN28 expression is detected in the gonocytes and the migrating, mitotically active germ cells of the fetal testis. Postnatal expression of LIN28 A and B showed differential expression, with LIN28A expressed in the undifferentiated spermatogonia and LIN28B in the elongating spermatids and Leydig cells. LIN28 interferes with many signaling pathways, leading to cell proliferation, and it is involved in important testicular physiological processes, such as cell renewal, maturation, fertility, and aging. In addition, aberrant LIN28 expression is associated with testicular cancer and testicular disorders, such as hypogonadotropic hypogonadism and Klinefelter’s syndrome. This comprehensive review encompasses current knowledge of the function of LIN28 paralogs in testis and other tissues and cells because many studies suggest LIN28AB as a promising target for developing novel therapeutic agents. Full article

(This article belongs to the Special Issue Development and Function of the Reproductive System)

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