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The Factors and Pathways Regulating the Activation of Mammalian Primordial Follicles in vivo.

ABSTRACT: Mammalian ovaries consist of follicles as basic functional units. Each follicle comprised an innermost oocyte and several surrounding flattened granulosa cells. Unlike males, according to the initial size of the primordial follicle pool and the rate of its activation and depletion, a female's reproductive life has been determined early in life. Primordial follicles, once activated, will get into an irreversible process of development. Most follicles undergo atretic degeneration, and only a few of them could mature and ovulate. Although there are a lot of researches contributing to exploring the activation of primordial follicles, little is known about its underlying mechanisms. Thus, in this review, we collected the latest papers and summarized the signaling pathways as well as some factors involved in the activation of primordial follicles, hoping to lead to a more profound understanding of the cellular and molecular mechanisms of primordial follicle activation.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7554314 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The Factors and Pathways Regulating the Activation of Mammalian Primordial Follicles <i>in vivo</i>.

Chen Yao Y Yang Weina W Shi Xu X Zhang Chenlu C Song Ge G Huang Donghui D

Frontiers in cell and developmental biology 20200930

Mammalian ovaries consist of follicles as basic functional units. Each follicle comprised an innermost oocyte and several surrounding flattened granulosa cells. Unlike males, according to the initial size of the primordial follicle pool and the rate of its activation and depletion, a female's reproductive life has been determined early in life. Primordial follicles, once activated, will get into an irreversible process of development. Most follicles undergo atretic degeneration, and only a few o ...[more]

PMID: 33102482

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Project description:BackgroundFor the first time, thorough morphometrical measurements of primordial ovarian follicles were performed and their age-related changes were investigated in Lithuanian women of the reproductive age.MethodsOvaries of dead women (n = 30) were divided into six age groups: 15-20 years old, 21-25 years old, 26-30 years old, 31-35 years old, 36-40 years old and 41-46 years old. Histological slides of left and right ovaries were stained using haematoxylin-eosin and periodic acid-Schiff (PAS) staining methods. The morphometrical measurements of 10 primordial ovarian follicles of the left and right ovary of each woman were made from microphotographs.ResultsThe diameter of primordial ovarian follicles increased in groups of women from 15 years old to 35 years old and decreased in the groups from 36 years old to 46 years old. The area of primordial ovarian follicles increased in the groups of women until 35 years old. It decreased in the groups of women older than 36 years. The follicular basement membrane thickened from 1.29 ± 0.11 μm to 1.43 ± 0.18 μm with increasing age of women. The diameter of primary oocytes enlarged until 35 years and then began to decrease. The area of primary oocytes increased in women until 35 years. It decreased in groups of women aged 36-40 and 41-46 years old. The diameter and the area of primary oocytes nuclei increased in women aged 15-30 years old; later, it began to decrease. The length of follicular cells varied from 8.56 ± 0.43 μm to 8.72 ± 0.27 μm (p > 0.05). The height of follicular cells varied from 2.59 ± 0.27 μm to 2.7 ± 0.21 μm (p > 0.05). The diameter, the area and the basement membrane thickness of primordial ovarian follicles and the diameter and the area of primary oocytes and their nuclei differed insignificantly in left and right ovaries in all age groups of women (p > 0.5). The length and height of follicular cells were similar in left and right ovaries of the same age group (p > 0.5).ConclusionsThe age decreasing of morphometrical parameters begins in primordial ovarian follicles and their primary oocytes in Lithuanian women older than 35 years. The thickness of the follicular basement membrane increased with increasing age of women. No significant differences were found in the morphometrical parameters in primordial follicles of left and right ovaries in the same age group of women.

Project description:IntroductionThe non-growing, meiotically-arrested oocytes housed within primordial follicles are exquisitely sensitive to genotoxic insults from endogenous and exogenous sources. Even a single DNA double-strand break (DSB) can trigger oocyte apoptosis, which can lead to accelerated depletion of the ovarian reserve, early loss of fertility and menopause. Therefore, repair of DNA damage is important for preserving the quality of oocytes to sustain fertility across the reproductive lifespan. This study aimed to evaluate the role of KU80 (encoded by the XRCC5 gene) - an essential component of the non-homologous end joining (NHEJ) pathway - in the repair of oocyte DNA DSBs during reproductive ageing, and following insult caused by the DNA-damaging chemotherapies cyclophosphamide and cisplatin.MethodsTo investigate the importance of KU80 following endogenous and exogenous DNA damage, ovaries from conditional oocyte-specific Xrcc5 knockout (Xrcc5 cKO) and wildtype (WT) mice that were aged or exposed to DNA damage-inducing chemotherapy were compared. Ovarian follicles and oocytes were quantified, morphologically assessed and analysed via immunohistochemistry for markers of DNA damage and apoptosis. In addition, chemotherapy exposed mice were superovulated, and the numbers and quality of mature metaphase- II (MII) oocytes were assessed.ResultsThe number of healthy follicles, atretic (dying) follicles, and corpora lutea were similar in Xrcc5 cKO and WT mice at PN50, PN200 and PN300. Additionally, primordial follicle number and ovulation rates were similar in young adult Xrcc5 cKO and WT mice following treatment with cyclophosphamide (75mg/kg), cisplatin (4mg/kg), or vehicle control (saline). Furthermore, KU80 was not essential for the repair of exogenously induced DNA damage in primordial follicle oocytes.DiscussionThese data indicate that KU80 is not required for maintenance of the ovarian reserve, follicle development, or ovulation during maternal ageing. Similarly, this study also indicates that KU80 is not required for the repair of exogenously induced DSBs in the prophase-arrested oocytes of primordial follicles.

Dataset Information

The Factors and Pathways Regulating the Activation of Mammalian Primordial Follicles in vivo.

Publications

The Factors and Pathways Regulating the Activation of Mammalian Primordial Follicles <i>in vivo</i>.

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