The role of autophagy during murine primordial follicle assembly

Sun, Ying; Wang, Yong-Yong; Sun, Xiao‐Feng; Cheng, Shun‐Feng; Li, Lan; Zhao, Yong; Shen, Wei; Chen, Hong

doi:10.18632/aging.101376

Cited by 43 publications

(29 citation statements)

References 52 publications

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“…In contrast, two other studies from Watanabe and Kimura (2018) and Watanabe, Sasaki, and Kimura (2019) shortly thereafter found that extension of this neonatal starvation period results in augmented primordial follicle formation in the first few days of life. This finding dovetails with studies from Sun et al (2018), who demonstrated that same effect by treating late embryonic mouse ovaries in vitro with rapamycin, an autophagy inducer, and finding increased oocyte retention in early postnatal life. However, these oocytes are contained within cysts and are delayed in primordial follicle formation.…”

Section: Diverse Cell Death Pathways Facilitate Primordial Follicle Asupporting

confidence: 88%

Pathways coordinating oocyte attrition and abundance during mammalian ovarian reserve establishment

Grive

2020

Molecular Reproduction Devel

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The mammalian ovarian reserve is comprised of a finite pool of primordial follicles, representing the lifetime reproductive capacity of females. In most mammals, the reserve is produced during embryonic and early postnatal development with oocyte numbers peaking during mid‐to‐late gestation, and then experiencing a dramatic decline continuing until shortly after birth. Oocytes remaining after the bulk of this attrition are subsequently surrounded by a layer of somatic pre‐granulosa cells with these units then referred to as “primordial follicles.” The complex and varied cell death mechanisms intrinsic to this process are not only characteristic of, but also essential for, the proper formation of this pool of follicles, and as a result must be immaculately balanced to ensure long‐term fertility and reproductive health. Too few follicles can lead to Primary Ovarian Insufficiency, resulting in fertility loss and other features of aging, such as an overall shorter lifespan. On the other hand, whereas an excess of follicles might extend reproductive lifespan, this might also be the underlying etiology of other ovarian pathologies. The last decade, in particular, has vastly expanded our understanding of oocyte attrition and determinants of ovarian reserve abundance. By continuing to decipher the intricacies underlying the cell death processes and development of the initial primordial follicle pool, we may be in a much better position to understand idiopathic cases of premature follicle depletion and improve ovarian health in reproductive‐age women.

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Section: Diverse Cell Death Pathways Facilitate Primordial Follicle Asupporting

confidence: 88%

Pathways coordinating oocyte attrition and abundance during mammalian ovarian reserve establishment

Grive

2020

Molecular Reproduction Devel

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“…Recently, the importance of epigenetic modification in regulating somatic cell reprogramming as well as early embryo development has been widely reported (Liu et al, ; Matoba & Zhang, ; Yu et al, ). However, only a handful of studies have indicated that epigenetic modification plays an important role in controlling oocyte PCD during PF pool establishment (Sun et al, , ). Most recent studies uncovered the potential role of LSD1, in mediating autophagy in various cell types (Ambrosio et al, ; Byun et al, ; Periz et al, ).…”

Section: Introductionmentioning

confidence: 99%

LSD1 contributes to programmed oocyte death by regulating the transcription of autophagy adaptor SQSTM1/p62

Zhang

Zhu

et al. 2020

Aging Cell

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In female mammals, the size of the initially established primordial follicle (PF) pool within the ovaries determines the reproductive lifespan of females. Interestingly, the establishment of the PF pool is accompanied by a remarkable programmed oocyte loss for unclear reasons. Although apoptosis and autophagy are involved in the process of oocyte loss, the underlying mechanisms require substantial study. Here, we identify a new role of lysine‐specific demethylase 1 (LSD1) in controlling the fate of oocytes in perinatal mice through regulating the level of autophagy. Our results show that the relatively higher level of LSD1 in fetal ovaries sharply reduces from 18.5 postcoitus (dpc). Meanwhile, the level of autophagy increases while oocytes are initiating programmed death. Specific disruption of LSD1 resulted in significantly increased autophagy and obviously decreased oocyte number compared with the control. Conversely, the oocyte number is remarkably increased by the overexpression of Lsd1 in ovaries. We further demonstrated that LSD1 exerts its role by regulating the transcription of p62 and affecting autophagy level through its H3K4me2 demethylase activity. Finally, in physiological conditions, a decrease in LSD1 level leads to an increased level of autophagy in the oocyte when a large number of oocytes are being lost. Collectively, LSD1 may be one of indispensible epigenetic molecules who protects oocytes against preterm death through repressing the autophagy level in a time‐specific manner. And epigenetic modulation contributes to programmed oocyte death by regulating autophagy in mice.

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“…As it is known, two-thirds of germ cells are lost during the process of primordial follicle assembly of most mammals 8,14 . Over the last two decades, the reasons for the loss of the germ cells were extensively studied and apoptosis and autophagy are considered to be the two privileged mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…1a), which suggested a role of miR-378-3p in germ cell cyst break down and primordial follicle assembly. Since autophagy is reported to be involved in primordial follicle assembly 12,14 , we cultured newborn mouse ovaries in vitro for 3 days in the presence of rapamycin and 3-methyladenine, two well-known activator and inhibitor of autophagy, respectively. The results showed a ∼5-fold increased expression of miR-378-3p in the presence of rapamycin (Fig.…”

Section: Mir-378-3p Regulates Autophagy During Primordial Follicle Asmentioning

confidence: 99%

“…Also autophagy is reported to be involved in primordial follicle assembly. In fact, autophagy is confirmed to be active in mice perinatal ovary to prevent germ cell overloss 12,13 , probably because active autophagy can accumulate nutrient substances to better supply the surviving oocyte 14 . It is well known that autophagy can be induced by starvation [15][16][17] .…”

Section: Introductionmentioning

confidence: 99%

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miR-378-3p maintains the size of mouse primordial follicle pool by regulating cell autophagy and apoptosis

et al. 2020

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Primordial follicle pool provides all available oocytes throughout the whole reproductive life span. Abnormal regulation in primordial follicle assembly leads to abnormal size of primordial follicle pool, even causes infertility. Here, miR-378-3p was proved to regulate mouse primordial follicle assembly both in vivo and in vitro. The expression of miR-378-3p significantly increased in mice ovaries from 17.5 dpc (days post coitum) up to 3 dpp (day post partum) compared with the expression of 16.5 dpc ovaries, which suggested that miR-378-3p was involved in primordial follicle assembly. To uncover the underlying mechanism, newborn mice ovaries were cultured in vitro in the presence of rapamycin and 3-methyladenine, which showed that the expression of miR-378-3p changed together with the percentage of primordial follicle. Moreover, during the normal process of primordial follicle assembly between 17.6 dpc and 3 dpp, autophagy is activated, while, apoptosis is inhibited. The in vivo results showed that newborn mice starved for 1.5 days showing the increased miR-378-3p, activated autophagy and inhibited apoptosis in the ovaries, had more percentage of primordial follicles. Over-expression of miR-378-3p using miR-378-3p agomir caused increased percentage of primordial follicle, increased level of autophagy, and decreased level of apoptosis. Knockdown of miR-378-3p by miR-378-3p antiagomir had the opposite results. Using pmirGLO Dual-Luciferase miRNA Target Expression system, we confirmed both PDK1 and Caspase9 were targets of miR-378-3p, which suggested that miR-378-3p activated autophagy by targeting PDK1 and inhibited apoptosis by targeting Caspase9. MiR-378-3p could be used as a biomarker of diseases caused by abnormal size of primordial follicle pool for diagnosis, prevention, or therapy.

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The role of autophagy during murine primordial follicle assembly

Cited by 43 publications

References 52 publications

Pathways coordinating oocyte attrition and abundance during mammalian ovarian reserve establishment

Pathways coordinating oocyte attrition and abundance during mammalian ovarian reserve establishment

LSD1 contributes to programmed oocyte death by regulating the transcription of autophagy adaptor SQSTM1/p62

miR-378-3p maintains the size of mouse primordial follicle pool by regulating cell autophagy and apoptosis

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