Molecular Mechanism of Oocyte Maturation

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Reproductive Cells and Development".

Deadline for manuscript submissions: closed (15 November 2021) | Viewed by 48558

Special Issue Editor


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Guest Editor
Center for Reproductive Medicine, Shanghai 10th People’s Hospital of Tongji University, Shanghai 200072, China
Interests: oocyte; cumulus cell; granulosa cell; in vitro maturation; fertilization; embryo

Special Issue Information

Dear Colleagues,

Assisted reproductive technology (ART) has helped several million women to overcome childlessness due to infertility. For the infertility treatment with ART, the key issue is the source of oocytes. Although the first human live birth resulting from in vitro fertilization (IVF) was produced by natural cycle IVF, this procedure has been gradually replaced by ovarian hyperstimulation combined with IVF treatment, because the number of oocytes retrieved determines the number of embryos available for transfer which, in turn, directly affects the chance of a successful pregnancy.

Since the 1930s, oocyte maturation has been studied in vivo and in vitro, and the knowledge of molecular mechanism of oocyte maturation obtained rapidly, especially in recent years based on the development of advanced technology of molecular biology. It was discovered that oocytes could resume meiosis spontaneously without LH stimulation when they were liberated from the follicles and cultured under simple medium. Interestingly, the time course of spontaneous maturation is similar to that of LH surge in vivo. This observation has led to general acceptance of the hypothesis that the follicular granulosa cells prevent the precocious resumption of meiosis until the LH surge before ovulation. The regulation of oocyte meiotic prophase arrest and resumption involves many factors related to the follicle, including the interaction of oocyte, cumulus cells, and mural granulosa cells.

In this Special Issue, we will summarize the molecular mechanism of oocyte maturation in order to provide our readers more information about oocyte maturation in vivo and in vitro, in which may stimulate our readers to understand more clearly from basic science to clinical practice with oocyte maturation in vivo and in vitro for infertility treatment.

We look forward to your contributions.

Prof. Dr. Richeng Chian
Guest Editor

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Keywords

  • oocyte
  • maturation
  • in vivo
  • in vitro
  • fertilization
  • cumulus cells
  • granulosa cells
  • IVF

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Published Papers (7 papers)

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Research

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18 pages, 4535 KiB  
Article
Changes in the Mitochondria-Related Nuclear Gene Expression Profile during Human Oocyte Maturation by the IVM Technique
by Zhi-Yong Yang, Min Ye, Ya-Xin Xing, Qi-Gui Xie, Jian-Hong Zhou, Xin-Rui Qi, Kehkooi Kee and Ri-Cheng Chian
Cells 2022, 11(2), 297; https://doi.org/10.3390/cells11020297 - 16 Jan 2022
Cited by 7 | Viewed by 3010
Abstract
To address which mitochondria-related nuclear differentially expressed genes (DEGs) and related pathways are altered during human oocyte maturation, single-cell analysis was performed in three oocyte states: in vivo matured (M-IVO), in vitro matured (M-IVT), and failed to mature in vitro (IM-IVT). There were [...] Read more.
To address which mitochondria-related nuclear differentially expressed genes (DEGs) and related pathways are altered during human oocyte maturation, single-cell analysis was performed in three oocyte states: in vivo matured (M-IVO), in vitro matured (M-IVT), and failed to mature in vitro (IM-IVT). There were 691 DEGs and 16 mitochondria-related DEGs in the comparison of M-IVT vs. IM-IVT oocytes, and 2281 DEGs and 160 mitochondria-related DEGs in the comparison of M-IVT vs. M-IVO oocytes, respectively. The GO and KEGG analyses showed that most of them were involved in pathways such as oxidative phosphorylation, pyruvate metabolism, peroxisome, and amino acid metabolism, i.e., valine, leucine, isoleucine, glycine, serine, and threonine metabolism or degradation. During the progress of oocyte maturation, the metabolic pathway, which derives the main source of ATP, shifted from glucose metabolism to pyruvate and fatty acid oxidation in order to maintain a low level of damaging reactive oxygen species (ROS) production. Although the immature oocytes could be cultured to a mature stage by an in vitro technique (IVM), there were still some differences in mitochondria-related regulations, which showed that the mitochondria were regulated by nuclear genes to compensate for their developmental needs. Meanwhile, the results indicated that the current IVM culture medium should be optimized to compensate for the special need for further development according to this disclosure, as it was a latent strategy to improve the effectiveness of the IVM procedure. Full article
(This article belongs to the Special Issue Molecular Mechanism of Oocyte Maturation)
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15 pages, 2387 KiB  
Article
Bitter Taste Receptors Expression in Human Granulosa and Cumulus Cells: New Perspectives in Female Fertility
by Bianca Semplici, Francesca Paola Luongo, Sofia Passaponti, Claudia Landi, Laura Governini, Giuseppe Morgante, Vincenzo De Leo, Paola Piomboni and Alice Luddi
Cells 2021, 10(11), 3127; https://doi.org/10.3390/cells10113127 - 11 Nov 2021
Cited by 14 | Viewed by 3022
Abstract
Bitter taste receptors (TAS2RS) expression is not restricted to the oral cavity and the presence of these receptors in the male reproductive system and sperm provides insights into their possible role in human reproduction. To elucidate the potential role of TAS2Rs in the [...] Read more.
Bitter taste receptors (TAS2RS) expression is not restricted to the oral cavity and the presence of these receptors in the male reproductive system and sperm provides insights into their possible role in human reproduction. To elucidate the potential role of TAS2Rs in the female reproductive system, we investigated the expression and localization of bitter taste receptors and the components of signal transduction cascade involved in the pathway of taste receptors in somatic follicular cells obtained from women undergoing assisted reproductive techniques. We found that TAS2R genes are expressed in both cumulus (CCs) and granulosa (GCs) cells, with TAS2R14 being the most highly expressed bitter receptor subtype. Interestingly, a slight increase in the expression of TAS2R14 and TAS2R43 was shown in both GCs and CCs in young women (p < 0.05), while a negative correlation may be established between the number of oocytes collected at the pickup and the expression of TAS2R43. Regarding α-gustducin and α-transducin, two Gα subunits expressed in the taste buds on the tongue, we provide evidence for their expression in CCs and GCs, with α-gustducin showing two additional isoforms in GCs. Finally, we shed light on the possible downstream transduction pathway initiated by taste receptor activation in the female reproductive system. Our study, showing for the first time the expression of taste receptors in the somatic ovarian follicle cells, significantly extends the current knowledge of the biological role of TAS2Rs for human female fertility. Full article
(This article belongs to the Special Issue Molecular Mechanism of Oocyte Maturation)
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13 pages, 2926 KiB  
Article
Upregulation of Low-Density Lipoprotein Receptor of the Steroidogenesis Pathway in the Cumulus Cells Is Associated with the Maturation of Oocytes and Achievement of Pregnancy
by Myung Joo Kim, Young Sang Kim, Yu Jin Kim, Hye Ran Lee, Kyoung Hee Choi, Eun A Park, Ki Ye Kang, Tae Ki Yoon, Sohyun Hwang, Jung Jae Ko, You Shin Kim and Jae Ho Lee
Cells 2021, 10(9), 2389; https://doi.org/10.3390/cells10092389 - 11 Sep 2021
Cited by 6 | Viewed by 2535
Abstract
The maturation of the oocyte is influenced by cumulus cells (CCs) and associated with pregnancy rate, whereas the influencing factors have not been completely elucidated in the CCs. In this study, we identified new regulators of CCs for high-quality oocytes and successful pregnancies [...] Read more.
The maturation of the oocyte is influenced by cumulus cells (CCs) and associated with pregnancy rate, whereas the influencing factors have not been completely elucidated in the CCs. In this study, we identified new regulators of CCs for high-quality oocytes and successful pregnancies during assisted reproductive techniques. CCs were collected from cumulus–oocyte complexes (COCs) in young (≤33 years old) and old (≥40 years old) women undergoing intracytoplasmic sperm injection (ICSI) procedures. We screened for factors differentially expressed between young vs. old CCs and pregnancy vs. non-pregnancy using whole mRNA-seq-next-generation sequencing (NGS). We characterized the transcriptome of the CCs to identify factors critical for achieving pregnancy in IVF cycles. Women in the young and old pregnancy groups exhibited the up- and downregulation of multiple genes compared with the non-pregnancy groups, revealing the differential regulation of several specific genes involved in ovarian steroidogenesis in CCs. It was shown that the low-density lipoprotein (LDL) receptor to the steroidogenesis pathway was upregulated in CCs with higher maturity rates of oocytes in the pregnancy group. In conclusion, a higher pregnancy rate is related to the signaling pathway of steroidogenesis by the LDL receptor in infertile women undergoing IVF procedures. Full article
(This article belongs to the Special Issue Molecular Mechanism of Oocyte Maturation)
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14 pages, 3273 KiB  
Article
miR-135a Suppresses Granulosa Cell Growth by Targeting Tgfbr1 and Ccnd2 during Folliculogenesis in Mice
by Lei Wang, Yaru Chen, Shang Wu, Jinhua Tang, Gaogui Chen and Fenge Li
Cells 2021, 10(8), 2104; https://doi.org/10.3390/cells10082104 - 17 Aug 2021
Cited by 8 | Viewed by 2930
Abstract
The success of female reproduction relies on high quality oocytes, which is determined by well-organized cooperation between granulosa cells (GCs) and oocytes during folliculogenesis. GC growth plays a crucial role in maintaining follicle development. Herein, miR-135a was identified as a differentially expressed microRNA [...] Read more.
The success of female reproduction relies on high quality oocytes, which is determined by well-organized cooperation between granulosa cells (GCs) and oocytes during folliculogenesis. GC growth plays a crucial role in maintaining follicle development. Herein, miR-135a was identified as a differentially expressed microRNA in pre-ovulatory ovarian follicles between Large White and Chinese Taihu sows detected by Solexa deep sequencing. We found that miR-135a could significantly facilitate the accumulation of cells arrested at the G1/S phase boundary and increase apoptosis. Mechanically, miR-135a suppressed transforming growth factor, beta receptor I (Tgfbr1) and cyclin D2 (Ccnd2) expression by targeting their 3′UTR in GCs. Furthermore, subcellular localization analysis and a chromatin immunoprecipitation-quantitative real-time PCR (ChIP-qPCR) assay demonstrated that the TGFBR1-SMAD3 pathway could enhance Ccnd2 promoter activity and thus upregulate Ccnd2 expression. Finally, estrogen receptor 2 (ESR2) functioned as a transcription factor by directly binding to the miR-135a promoter region and decreasing the transcriptional activity of miR-135a. Taken together, our study reveals a pro-survival mechanism of ESR2/miR-135a/Tgfbr1/Ccnd2 axis for GC growth, and also provides a novel target for the improvement of female fertility. Full article
(This article belongs to the Special Issue Molecular Mechanism of Oocyte Maturation)
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Review

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17 pages, 626 KiB  
Review
The Role of Mitochondria in Oocyte Maturation
by Anastasia Kirillova, Johan E. J. Smitz, Gennady T. Sukhikh and Ilya Mazunin
Cells 2021, 10(9), 2484; https://doi.org/10.3390/cells10092484 - 19 Sep 2021
Cited by 156 | Viewed by 12654
Abstract
With the nucleus as an exception, mitochondria are the only animal cell organelles containing their own genetic information, called mitochondrial DNA (mtDNA). During oocyte maturation, the mtDNA copy number dramatically increases and the distribution of mitochondria changes significantly. As oocyte maturation requires a [...] Read more.
With the nucleus as an exception, mitochondria are the only animal cell organelles containing their own genetic information, called mitochondrial DNA (mtDNA). During oocyte maturation, the mtDNA copy number dramatically increases and the distribution of mitochondria changes significantly. As oocyte maturation requires a large amount of ATP for continuous transcription and translation, the availability of the right number of functional mitochondria is crucial. There is a correlation between the quality of oocytes and both the amount of mtDNA and the amount of ATP. Suboptimal conditions of in vitro maturation (IVM) might lead to changes in the mitochondrial morphology as well as alternations in the expression of genes encoding proteins associated with mitochondrial function. Dysfunctional mitochondria have a lower ability to counteract reactive oxygen species (ROS) production which leads to oxidative stress. The mitochondrial function might be improved with the application of antioxidants and significant expectations are laid on the development of new IVM systems supplemented with mitochondria-targeted reagents. Different types of antioxidants have been tested already on animal models and human rescue IVM oocytes, showing promising results. This review focuses on the recent observations on oocytes’ intracellular mitochondrial distribution and on mitochondrial genomes during their maturation, both in vivo and in vitro. Recent mitochondrial supplementation studies, aiming to improve oocyte developmental potential, are summarized. Full article
(This article belongs to the Special Issue Molecular Mechanism of Oocyte Maturation)
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18 pages, 1782 KiB  
Review
The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization
by Bongkoch Turathum, Er-Meng Gao and Ri-Cheng Chian
Cells 2021, 10(9), 2292; https://doi.org/10.3390/cells10092292 - 2 Sep 2021
Cited by 138 | Viewed by 15997
Abstract
Cumulus cells (CCs) originating from undifferentiated granulosa cells (GCs) differentiate in mural granulosa cells (MGCs) and CCs during antrum formation in the follicle by the distribution of location. CCs are supporting cells of the oocyte that protect the oocyte from the microenvironment, which [...] Read more.
Cumulus cells (CCs) originating from undifferentiated granulosa cells (GCs) differentiate in mural granulosa cells (MGCs) and CCs during antrum formation in the follicle by the distribution of location. CCs are supporting cells of the oocyte that protect the oocyte from the microenvironment, which helps oocyte growth and maturation in the follicles. Bi-directional communications between an oocyte and CCs are necessary for the oocyte for the acquisition of maturation and early embryonic developmental competence following fertilization. Follicle-stimulation hormone (FSH) and luteinizing hormone (LH) surges lead to the synthesis of an extracellular matrix in CCs, and CCs undergo expansion to assist meiotic resumption of the oocyte. The function of CCs is involved in the completion of oocyte meiotic maturation and ovulation, fertilization, and subsequent early embryo development. Therefore, understanding the function of CCs during follicular development may be helpful for predicting oocyte quality and subsequent embryonic development competence, as well as pregnancy outcomes in the field of reproductive medicine and assisted reproductive technology (ART) for infertility treatment. Full article
(This article belongs to the Special Issue Molecular Mechanism of Oocyte Maturation)
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17 pages, 4735 KiB  
Review
Current Understandings of Core Pathways for the Activation of Mammalian Primordial Follicles
by Yu Zhao, Haiwei Feng, Yihui Zhang, Jian V. Zhang, Xiaohui Wang, Dongteng Liu, Tianren Wang, Raymond H. W. Li, Ernest H. Y. Ng, William S. B. Yeung, Kenny A. Rodriguez-Wallberg and Kui Liu
Cells 2021, 10(6), 1491; https://doi.org/10.3390/cells10061491 - 13 Jun 2021
Cited by 32 | Viewed by 6376
Abstract
The mammalian ovary has two main functions—producing mature oocytes for fertilization and secreting hormones for maintaining the ovarian endocrine functions. Both functions are vital for female reproduction. Primordial follicles are composed of flattened pre-granulosa cells and a primary oocyte, and activation of primordial [...] Read more.
The mammalian ovary has two main functions—producing mature oocytes for fertilization and secreting hormones for maintaining the ovarian endocrine functions. Both functions are vital for female reproduction. Primordial follicles are composed of flattened pre-granulosa cells and a primary oocyte, and activation of primordial follicles is the first step in follicular development and is the key factor in determining the reproductive capacity of females. The recent identification of the phosphatidylinositol 3 kinase (PI3K)/phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling pathway as the key controller for follicular activation has made the study of primordial follicle activation a hot research topic in the field of reproduction. This review systematically summarizes the roles of the PI3K/PTEN signaling pathway in primordial follicle activation and discusses how the pathway interacts with various other molecular networks to control follicular activation. Studies on the activation of primordial follicles have led to the development of methods for the in vitro activation of primordial follicles as a treatment for infertility in women with premature ovarian insufficiency or poor ovarian response, and these are also discussed along with some practical applications of our current knowledge of follicular activation. Full article
(This article belongs to the Special Issue Molecular Mechanism of Oocyte Maturation)
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