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Germ Cells Molecular Research and Application
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Germ Cells Molecular Research and Application

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 (31 May 2023) | Viewed by 13025

Special Issue Editor

Dr. Stefania Gonfloni

E-Mail Website
Guest Editor
Department of Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, 00133 Rome, Italy
Interests: molecular biology; post translational modifications; phosphorylation; tyrosine kinases; cell signaling pathways
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Female reproductive health depends on a finite pool of primordial follicles, established before birth, named the ovarian reserve. Mammalian follicles require close contacts and interaction between oocytes and surrounding granulosa cells for their development. Yet, regulatory signaling mechanisms underlying folliculogenesis remain to be fully elucidated. Physical contacts, as well as biochemical crosstalk between somatic cells and oocytes, cannot be reconstituted by traditional 2D cultures, and animal experimentation has been considered the gold standard for these studies. Despite their clear value, extrapolations of animal data to human health remain inefficient. Further knowledge in this field can benefit greatly from the development of 3D-culture systems of human ovarian tissue to evaluate follicle development and microenvironment, with important implications for human reproduction.

In this Special Issue, we welcome original research articles, reviews, and perspectives elucidating the mechanisms involved in follicle development and the maintenance of ovarian reserve. 

Dr. Stefania Gonfloni
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

  • follicle development
  • premature ovarian insufficiency
  • signal transduction
  • apoptosis
  • autophagy
  • aging
  • reproductive biotechnology
  • organ-on-chip

Published Papers (5 papers)

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Research

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16 pages, 9694 KiB  
Article
miR-486 Responds to Apoptosis and Autophagy by Repressing SRSF3 Expression in Ovarian Granulosa Cells of Dairy Goats
by Shujuan Liu, Qiqi Bu, Jiashun Tong, Zhanhang Wang, Jiuzeng Cui, Heran Cao, Haidong Ma, Binyun Cao, Xiaopeng An and Yuxuan Song
Int. J. Mol. Sci. 2023, 24(10), 8751; https://doi.org/10.3390/ijms24108751 - 15 May 2023
Cited by 1 | Viewed by 1203
Abstract
The accumulation of ovarian granulosa cell (GC) apoptosis underlies follicular atresia. By comparing the previous sequencing results, miR-486 was found to be differentially expressed at higher levels in the monotocous goat than in the polytocous goat. Unfortunately, the miRNA-mediated mechanisms by which the [...] Read more.
The accumulation of ovarian granulosa cell (GC) apoptosis underlies follicular atresia. By comparing the previous sequencing results, miR-486 was found to be differentially expressed at higher levels in the monotocous goat than in the polytocous goat. Unfortunately, the miRNA-mediated mechanisms by which the GC fate is regulated are unknown in Guanzhong dairy goats. Therefore, we investigated miR-486 expression in small and large follicles, as well as its impact on normal GC survival, apoptosis and autophagy in vitro. Here, we identified and characterized miR-486 interaction with Ser/Arg-rich splicing factor 3 (SRSF3) using luciferase reporter analysis, detecting its role in GC survival, apoptosis and autophagy regulation through qRT-PCR, Western blot, CCK-8, EdU, flow cytometry, mitochondrial membrane potential and monodansylcadaverine, etc. Our findings revealed prominent effects of miR-486 in the regulation of GC survival, apoptosis and autophagy by targeting SRSF3, which might explain the high differential expression of miR-486 in the ovaries of monotocous dairy goats. In summary, this study aimed to reveal the underlying molecular mechanism of miR-486 regulation on GC function and its effect on ovarian follicle atresia in dairy goats, as well as the functional interpretation of the downstream target gene SRSF3. Full article
(This article belongs to the Special Issue Germ Cells Molecular Research and Application)
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19 pages, 7190 KiB  
Article
Valproate Targets Mammalian Gastrulation Impairing Neural Tissue Differentiation and Development of the Placental Source In Vitro
by Ana Katušić-Bojanac, Milvija Plazibat, Marta Himelreich-Perić, Katarina Eck-Raković, Jure Krasić, Nino Sinčić, Gordana Jurić-Lekić, Davor Ježek and Floriana Bulić-Jakuš
Int. J. Mol. Sci. 2022, 23(16), 8861; https://doi.org/10.3390/ijms23168861 - 09 Aug 2022
Cited by 1 | Viewed by 1533
Abstract
The teratogenic activity of valproate (VPA), an antiepileptic and an inhibitor of histone deacetylase (HDACi), is dose-dependent in humans. Previous results showed that VPA impairs in vitro development and neural differentiation of the gastrulating embryo proper. We aimed to investigate the impact of [...] Read more.
The teratogenic activity of valproate (VPA), an antiepileptic and an inhibitor of histone deacetylase (HDACi), is dose-dependent in humans. Previous results showed that VPA impairs in vitro development and neural differentiation of the gastrulating embryo proper. We aimed to investigate the impact of a lower VPA dose in vitro and whether this effect is retained in transplants in vivo. Rat embryos proper (E9.5) and ectoplacental cones were separately cultivated at the air-liquid interface with or without 1 mM VPA. Embryos were additionally cultivated with HDACi Trichostatin A (TSA), while some cultures were syngeneically transplanted under the kidney capsule for 14 days. Embryos were subjected to routine histology, immunohistochemistry, Western blotting and pyrosequencing. The overall growth of VPA-treated embryos in vitro was significantly impaired. However, no differences in the apoptosis or proliferation index were found. Incidence of the neural tissue was lower in VPA-treated embryos than in controls. TSA also impaired growth and neural differentiation in vitro. VPA-treated embryos and their subsequent transplants expressed a marker of undifferentiated neural cells compared to controls where neural differentiation markers were expressed. VPA increased the acetylation of histones. Our results point to gastrulation as a sensitive period for neurodevelopmental impairment caused by VPA. Full article
(This article belongs to the Special Issue Germ Cells Molecular Research and Application)
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16 pages, 959 KiB  
Article
Melatonin Signaling Pathways Implicated in Metabolic Processes in Human Granulosa Cells (KGN)
by Arjoune Asma and Sirard Marc-André
Int. J. Mol. Sci. 2022, 23(6), 2988; https://doi.org/10.3390/ijms23062988 - 10 Mar 2022
Cited by 7 | Viewed by 2489
Abstract
Female reproduction depends on the metabolic status, especially during the period of folliculogenesis. Even though it is believed that melatonin can improve oocyte competence, there is still limited knowledge of how it can modulate metabolic processes during folliculogenesis and which signaling pathways are [...] Read more.
Female reproduction depends on the metabolic status, especially during the period of folliculogenesis. Even though it is believed that melatonin can improve oocyte competence, there is still limited knowledge of how it can modulate metabolic processes during folliculogenesis and which signaling pathways are involved in regulating gene expression. To investigate the effects of melatonin on metabolic signals during the antral stage of follicular development, human granulosa-like tumor cells (KGN) were treated with melatonin or forskolin, and gene expression was analyzed with RNA-seq technology. Following appropriate normalization and the application of a fold change cut-off of 1.5 (FC 1.5, p ≤ 0.05), 1009 and 922 genes were identified as differentially expressed in response to melatonin and forskolin, respectively. Analysis of major upstream regulators suggested that melatonin may activate PKB/mTOR signaling pathways to program the metabolism of KGN cells to support slower growth and differentiation and to prevent follicular atresia. Similarly, PKA activation through stimulation of cAMP synthesis with FSK seemed to exert the same effects as melatonin in reducing follicular growth and regulating differentiation. This study suggests that melatonin may act through PKA and PKB simultaneously in human granulosa cells to prevent follicular atresia and early luteinization at the antral stage. Full article
(This article belongs to the Special Issue Germ Cells Molecular Research and Application)
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Review

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17 pages, 1533 KiB  
Review
Female Germ Cell Development in Chickens and Humans: The Chicken Oocyte Enriched Genes Convergent and Divergent with the Human Oocyte
by Deivendran Rengaraj and Jae Yong Han
Int. J. Mol. Sci. 2022, 23(19), 11412; https://doi.org/10.3390/ijms231911412 - 27 Sep 2022
Cited by 5 | Viewed by 2676
Abstract
The development of germ cells and other physiological events in the differentiated ovary of humans are highly conserved with several mammalian species, except for the differences in timing. However, comparative knowledge on this topic is very scarce with respect to humans and lower [...] Read more.
The development of germ cells and other physiological events in the differentiated ovary of humans are highly conserved with several mammalian species, except for the differences in timing. However, comparative knowledge on this topic is very scarce with respect to humans and lower vertebrates, such as chickens. In chickens, female germ cells enter into meiosis around embryonic day (E) 15.5 and are arrested in meiotic prophase I as primary oocytes. The oocytes arrested in meiosis I are accumulated in germ-cell cysts; shortly after hatching, they are enclosed by flattened granulosa cells in order to form primordial follicles. In humans, the process of meiotic recombination in female germ cells begins in the 10–11th week of gestation, and primordial follicles are formed at around week 20. In this review, we comprehensively elucidate both the conservation and the species-specific differences between chickens and humans with respect to germ cell, oocyte, and follicle development. Importantly, we provide functional insights into a set of chicken oocyte enriched genes (from E16 to 1 week post-hatch) that show convergent and divergent expression patterns with respect to the human oocyte (from week 11 to 26). Full article
(This article belongs to the Special Issue Germ Cells Molecular Research and Application)
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16 pages, 807 KiB  
Review
MicroRNAs in the Regulation of Endometrial Receptivity for Embryo Implantation
by Manizha Shekibi, Sophea Heng and Guiying Nie
Int. J. Mol. Sci. 2022, 23(11), 6210; https://doi.org/10.3390/ijms23116210 - 01 Jun 2022
Cited by 25 | Viewed by 4313
Abstract
Development of endometrial receptivity is crucial for successful embryo implantation and pregnancy initiation. Understanding the molecular regulation underpinning endometrial transformation to a receptive state is key to improving implantation rates in fertility treatments such as IVF. With microRNAs (miRNAs) increasingly recognized as important [...] Read more.
Development of endometrial receptivity is crucial for successful embryo implantation and pregnancy initiation. Understanding the molecular regulation underpinning endometrial transformation to a receptive state is key to improving implantation rates in fertility treatments such as IVF. With microRNAs (miRNAs) increasingly recognized as important gene regulators, recent studies have investigated the role of miRNAs in the endometrium. Studies on miRNAs in endometrial disorders such as endometriosis and endometrial cancer have been reviewed previously. In this minireview, we aim to provide an up-to-date knowledge of miRNAs in the regulation of endometrial receptivity. Since endometrial remodelling differs considerably between species, we firstly summarised the key events of the endometrial cycle in humans and mice and then reviewed the miRNAs identified so far in these two species with likely functional significance in receptivity establishment. To date, 29 miRNAs have been reported in humans and 15 miRNAs in mice within various compartments of the endometrium that may potentially modulate receptivity; miRNAs regulating the Wnt signalling and those from the let-7, miR-23, miR-30, miR-200 and miR-183 families are found in both species. Future studies are warranted to investigate miRNAs as biomarkers and/or therapeutic targets to detect/improve endometrial receptivity in human fertility treatment. Full article
(This article belongs to the Special Issue Germ Cells Molecular Research and Application)
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