Deciphering the dynamics of the ovarian reser


image: Graphical abstract of this study. A total of 18 ovaries from 16 cynomolgus monkeys were collected and separated into five developmental stages: perinatal period (E140, 8-day-old [8 d]), preadolescence (1–3 years), adolescence (4–5 years), adulthood (6–15 years), and perimenopause (16–23 years). Immunofluorescent staining and H&E staining of ovaries were performed to investigate the dynamics of the cynomolgus monkey ovarian reserve and the establishment of the primordial follicle pool. Serum samples were collected to analyze the hormone levels.
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Credit: ©Science China Press

This study is led by Prof. Hongmei Wang (State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences), Prof. Lan Zhu (Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College), Prof. Xiaokui Yang (Department of Human Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University), and Dr. Long Yan (State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology , Chinese Academy of Sciences).

Female reproduction and health are highly dependent on ovarian function. Ovarian reserve is a critical indicator of ovarian function. A systematic study of the ovarian reserve covering the human lifespan would benefit the understanding and treatment of reproductive aging under physiological and pathological conditions. However, due to ethical constraints and limited access to intact disease-free human ovarian tissues, research on the ovarian reserve in healthy women throughout their lifespan is limited. Non-human primates share similar genetic and physiological properties with humans and are considered an ideal model for studying the human ovarian reserve covering the lifespan. However, to date, there is no literature on the ovarian reserve covering the lifespan of non-human primates.

Wan Tu et al. used modern stereology techniques to count follicles and revealed the dynamics of the cynomolgus monkey (Macaca fascicularis) ovarian reserve covering its lifespan. The number of primordial follicles decreased with age: perinatal period (1.5 × 105 on average), preadolescence (1.2 × 105 on average), adolescence (7.7 × 104 on average), adulthood (4.3 × 104 on average) and perimenopause (2.5 × 103 on average). These results suggested that the ovarian reserve was abundant in the perinatal monkey ovary, then sharply declined during adolescent and adult ovaries, finally exhausted in the perimenopausal monkey ovary.

To investigate the establishment of primordial follicle pool, they performed immunofluorescent staining and H&E staining of perinatal monkey ovaries. The results suggested that the establishment of the primordial follicle pool in cynomolgus monkeys was initiated before E90 and was accomplished in two weeks after birth. Accompanied by the dynamics of ovarian reserve, ovarian fibrosis and oxidative DNA damage level were increased significantly with age. Moreover, they found that the age-related trend in AMH (anti-Müllerian hormone) levels in cynomolgus monkeys was consistent with that in humans, suggesting that AMH could also be a predictor of ovarian reserve in cynomolgus monkeys.

In summary, they depicted the dynamics of the ovarian reserve in cynomolgus monkeys covering their lifespan, provided evidence to show the establishment of the primate primordial follicle pool, and the correlation between the dynamics of ovarian reserve and ovarian microenvironmental changes. This study provided a solid foundation for investigating the mechanisms of ovarian aging and reproductive medicine research.


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