Transforming Growth Factor-β Signaling Participates in the Maintenance of the Primordial Follicle Pool in the Mouse Ovary

Wang, Zhengpin; Mu, Xinyi; Guo, Meng; Wang, Yijing; Teng, Zhen; Mao, Guanping; Niu, Wanbao; Feng, Lizhao; Zhao, Lihua; Xia, Guoliang

doi:10.1074/jbc.m113.532952

Cited by 66 publications

(69 citation statements)

References 46 publications

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“…The sections were counterstained with hematoxylin, dehydrated, coverslipped with histomount reagent, and imaged using BMI4000B downright microscope (Leica). The number of proliferating pre-granulosa cells was counted in 2 serial sections of the largest cross-section of each ovary and was averaged, as described previously46.…”

Section: Methodsmentioning

confidence: 99%

Progesterone Receptor Membrane Component 1 Mediates Progesterone-Induced Suppression of Oocyte Meiotic Prophase I and Primordial Folliculogenesis

Guo

Zhang

Wang

et al. 2016

Sci Rep

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Well-timed progression of primordial folliculogenesis is essential for mammalian female fertility. Progesterone (P4) inhibits primordial follicle formation under physiological conditions; however, P4 receptor that mediates this effect and its underlying mechanisms are unclear. In this study, we used an in vitro organ culture system to show that progesterone receptor membrane component 1 (PGRMC1) mediated P4-induced inhibition of oocyte meiotic prophase I and primordial follicle formation. We found that membrane-impermeable BSA-conjugated P4 inhibited primordial follicle formation similar to that by P4. Interestingly, PGRMC1 and its partner serpine1 mRNA-binding protein 1 were highly expressed in oocytes in perinatal ovaries. Inhibition or RNA interference of PGRMC1 abolished the suppressive effect of P4 on follicle formation. Furthermore, P4-PGRMC1 interaction blocked oocyte meiotic progression and decreased intra-oocyte cyclic AMP (cAMP) levels in perinatal ovaries. cAMP analog dibutyryl cAMP reversed P4–PGRMC1 interaction-induced inhibition of meiotic progression and follicle formation. Thus, our results indicated that PGRMC1 mediated P4-induced suppression of oocyte meiotic progression and primordial folliculogenesis by decreasing intra-oocyte cAMP levels.

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Section: Methodsmentioning

confidence: 99%

Progesterone Receptor Membrane Component 1 Mediates Progesterone-Induced Suppression of Oocyte Meiotic Prophase I and Primordial Folliculogenesis

Guo

Zhang

Wang

et al. 2016

Sci Rep

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“…Deletion of both Tsc2 and Tsc1 caused premature activation of all PFs around the time of puberty due to elevated mTORC1 activity in oocytes, leading finally to POF. Using a mouse fetal ovary culture system, Wang et al (2014) demonstrated the role of TGFb in maintenance of the PF pool and regulating oocyte growth through activation of rpS6, but not via activation of Akt or Foxo3a.…”

Section: Pi3k/pten/akt and Tsc/mtor Pathwaysmentioning

confidence: 99%

PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: an update

Makker

Goel

Mahdi

2014

Journal of Molecular Endocrinology

174

115

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Abnormalities in ovarian function, including defective oogenesis and folliculogenesis, represent a key female reproductive deficiency. Accumulating evidence in the literature has shown that the PI3K/PTEN/Akt and TSC/mTOR signaling pathways are critical regulators of ovarian function including quiescence, activation, and survival of primordial follicles, granulosa cell proliferation and differentiation, and meiotic maturation of oocytes. Dysregulation of these signaling pathways may contribute to infertility caused by impaired follicular development, intrafollicular oocyte development, and ovulation. This article reviews the current state of knowledge of the functional role of the PI3K/PTEN/Akt and TSC/mTOR pathways during mammalian oogenesis and folliculogenesis and their association with female infertility.

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“…Appropriate expression of TGF‐β1 and TGF‐β receptor 1(TGF‐βR1) in the ovary promotes growth and differentiation of follicles as well as proliferation of ovarian granulosa cells . Overexpression of TGF‐β1 inhibits 17‐α hydroxylase activity through a direct non‐competitive mechanism, increases androgen synthesis, causes endocrine disorders, and further inhibits the growth and development of follicles, causing follicular dysplasia . In our experiments, TGF‐β1 and TGF‐βR1 expression were significantly increased by nano TiO 2 , resulting in excess production of androgen in theca cells and disorders in growth, development, proliferation, and maturation of follicles in female mice.…”

Section: Discussionmentioning

confidence: 66%

“…Transforming growth factor‐beta (TGF‐β) family members are clearly involved in regulation of ovarian function and follicular development . In particular, the TGF‐β pathway has been shown to regulate the development and apoptosis of primordial follicles through synergistic effects of PI3K/AKT/mT0R signaling and downstream regulation of the AKT/p70S6K‐rpS6/TSC/mTOR pathway, thus delaying POF …”

Section: Introductionmentioning

confidence: 99%

Suppression of ovarian follicle development by nano TiO₂ is associated with TGF‐β‐mediated signaling pathways

Zhou

Hong

et al. 2018

J Biomedical Materials Res

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Nanoparticulate titanium dioxide (nano TiO2) is extensively applied in biological tissue engineering materials, food additives, cosmetics, and sunscreens. Numerous studies to date have demonstrated that nano TiO2 penetrates through the digestive system and possibly the blood circulation, leading to accumulation in the ovary and consequent reproductive toxicity. However, the mechanisms underlying the toxic effects of nano TiO2 on the female reproductive system remain to be established. In this study, female mice were exposed to different doses of nano TiO2 (1.25, 2.5, or 5 mg/kg body weight) via intragastric administration for 60 consecutive days, followed by investigation of follicular development, regulation of TGF‐β‐mediated signaling pathways, and expression of the pathway components. Subchronic exposure to nano TiO2 induced a decrease in the number of primordial, secondary, and antral follicles and corpus luteum and concomitant increase in atretic follicles. Furthermore, follicular development disorder induced by nano TiO2 was associated with upregulation of TGF‐β1, TGF‐βR1, PTEN, and Foxo3a involved in cell growth and apoptosis and downregulation of several growth factors (PI3K, AKT, p‐mTOR, p70S6K, p‐p70S6K1, rpS6, p‐rpS6, TSC1, and TSC2) in mouse ovaries. Our data collectively implied that suppression of ovarian follicle development by nano TiO2 was triggered by dysfunction of the TGF‐β, PI3K/AKT/mTOR, and AKT/p70S6K‐rpS6/TSC/mTOR pathways. The adverse effects of nano TiO2 on follicular development highlights the necessity for caution in the use of nanomaterials in the food industry. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 414–422, 2019.

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Transforming Growth Factor-β Signaling Participates in the Maintenance of the Primordial Follicle Pool in the Mouse Ovary

Cited by 66 publications

References 46 publications

Progesterone Receptor Membrane Component 1 Mediates Progesterone-Induced Suppression of Oocyte Meiotic Prophase I and Primordial Folliculogenesis

Progesterone Receptor Membrane Component 1 Mediates Progesterone-Induced Suppression of Oocyte Meiotic Prophase I and Primordial Folliculogenesis

PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: an update

Suppression of ovarian follicle development by nano TiO₂ is associated with TGF‐β‐mediated signaling pathways

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Transforming Growth Factor-β Signaling Participates in the Maintenance of the Primordial Follicle Pool in the Mouse Ovary

Cited by 66 publications

References 46 publications

Progesterone Receptor Membrane Component 1 Mediates Progesterone-Induced Suppression of Oocyte Meiotic Prophase I and Primordial Folliculogenesis

Progesterone Receptor Membrane Component 1 Mediates Progesterone-Induced Suppression of Oocyte Meiotic Prophase I and Primordial Folliculogenesis

PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: an update

Suppression of ovarian follicle development by nano TiO2 is associated with TGF‐β‐mediated signaling pathways

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Suppression of ovarian follicle development by nano TiO₂ is associated with TGF‐β‐mediated signaling pathways