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

Guo, Meng; Zhang, Cheng; Wang, Yan; Feng, Lizhao; Wang, Zhengpin; Niu, Wanbo; Du, Xiaoyan; Wang, Tang; Li, Yuna; Wang, Chao; Chen, Zhenwen

doi:10.1038/srep36869

Cited by 35 publications

(19 citation statements)

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“…Regarding signalling pathways that are activated during oocyte maturation, significant down‐regulation of transcripts for proteins involved in mTORC1, Wnt, NF‐kB, MAP kinase and phosphatase signalling pathways was observed. It is worth noting that we also detected a more than twofold decrease in Pgrmc1, a receptor required to slow down oocyte meiotic progression (Guo et al , ; Table ). This decrease in Pgrmc1 in GV oocytes was confirmed by RT–qPCR experiments ().…”

Section: Resultssupporting

confidence: 55%

PATL 2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice

et al. 2018

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The genetic causes of oocyte meiotic deficiency (OMD), a form of primary infertility characterised by the production of immature oocytes, remain largely unexplored. Using whole exome sequencing, we found that 26% of a cohort of 23 subjects with OMD harboured the same homozygous nonsense pathogenic mutation in PATL2, a gene encoding a putative RNA‐binding protein. Using Patl2 knockout mice, we confirmed that PATL2 deficiency disturbs oocyte maturation, since oocytes and zygotes exhibit morphological and developmental defects, respectively. PATL2's amphibian orthologue is involved in the regulation of oocyte mRNA as a partner of CPEB. However, Patl2's expression profile throughout oocyte development in mice, alongside colocalisation experiments with Cpeb1, Msy2 and Ddx6 (three oocyte RNA regulators) suggest an original role for Patl2 in mammals. Accordingly, transcriptomic analysis of oocytes from WT and Patl2 −/− animals demonstrated that in the absence of Patl2, expression levels of a select number of highly relevant genes involved in oocyte maturation and early embryonic development are deregulated. In conclusion, PATL2 is a novel actor of mammalian oocyte maturation whose invalidation causes OMD in humans.

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Section: Resultssupporting

confidence: 55%

PATL 2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice

et al. 2018

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“…PGRMC1 localizes to endosomes, the endoplasmic reticulum (Nölte et al, 2000;Ahmed et al, 2010a), and the plasma membrane (Krebs et al, 2000), consistent with its highly conserved role in trafficking. In cancer, the best characterized trafficking target for PGRMC1 is the epidermal growth factor receptor (EGFR) tyrosine kinase (Ahmed et al, 2010a;Mir et al, 2012;Aizen and Thomas, 2015;Kabe et al, 2016), although PGRMC1 also increases plasma membrane pools of glucagon-like peptide-1 receptor and membrane progestin receptor a1, a plasma membrane progesterone receptor (Thomas et al, 2014;Zhang et al, 2014) that may be the target for PGRMC1-dependent progesterone signaling (Bashour and Wray, 2012;Peluso, 2013;Guo et al, 2016;Sun et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Insulin Receptor Plasma Membrane Levels Increased by the Progesterone Receptor Membrane Component 1

et al. 2018

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The insulin receptor (IR) is a ligand-activated receptor tyrosine kinase that has a key role in metabolism, cellular survival, and proliferation. Progesterone receptor membrane component 1 (PGRMC1) promotes cellular signaling via receptor trafficking and is essential for some elements of tumor growth and metastasis. In the present study, we demonstrate that PGRMC1 coprecipitates with IR. Furthermore, we show that PGRMC1 increases plasma membrane IR levels in multiple cell lines and decreases insulin binding at the cell surface. The findings have therapeutic applications because a small-molecule PGRMC1 ligand, AG205, also decreases plasma membrane IR levels. However, PGRMC1 knockdown via short hairpin RNA expression and AG205 treatment potentiated insulin-mediated phosphorylation of the IR signaling mediator AKT. Finally, PGRMC1 also increased plasma membrane levels of two key glucose transporters, GLUT-4 and GLUT-1. Our data support a role for PGRMC1 maintaining plasma membrane pools of the receptor, modulating IR signaling and function.

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“…Two PGRMC subtypes have been discovered: PGRMC1 (aka 25-DX) and PGRMC2 (105,106,108,110,111). These PGRMC have been implicated in normal mammalian ovarian function including primordial follicle development, luteal vascularization and normal onset reproductive senescence (107,110,112). Young women with reduced PGRMC2 expression in granulosa cells have been diagnosed with diminished ovarian reserve (113).…”

Section: Non-classical Progesterone Receptors In Kisspeptin Neuronsmentioning

confidence: 99%

Hypothalamic Astrocyte Development and Physiology for Neuroprogesterone Induction of the Luteinizing Hormone Surge

2020

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Neural circuits in female rats sequentially exposed to estradiol and progesterone underlie so-called estrogen positive feedback that induce the surge release of pituitary luteinizing hormone (LH) leading to ovulation and luteinization of the corpus hemorrhagicum. It is now well-established that gonadotropin releasing hormone (GnRH) neurons express neither the reproductively critical estrogen receptor-α (ERα) nor classical progesterone receptor (PGR). Estradiol from developing ovarian follicles acts on ERα-expressing kisspeptin neurons in the rostral periventricular region of the third ventricle (RP3V) to induce PGR expression, and kisspeptin release. Circulating estradiol levels that induce positive feedback also induce neuroprogesterone (neuroP) synthesis in hypothalamic astrocytes. This local neuroP acts on kisspeptin neurons that express PGR to augment kisspeptin expression and release needed to stimulate GnRH release, triggering the LH surge. In vitro and in vivo studies demonstrate that neuroP signaling in kisspeptin neurons occurs through membrane PGR activation of Src family kinase (Src). This signaling cascade has been also implicated in PGR signaling in the arcuate nucleus of the hypothalamus, suggesting that Src may be a common mode of membrane PGR signaling. Sexual maturation requires that signaling between neuroP synthesizing astrocytes, kisspeptin and GnRH neurons be established. Prior to puberty, estradiol does not facilitate the synthesis of neuroP in hypothalamic astrocytes. During pubertal development, levels of membrane ERα increase in astrocytes coincident with an increase of PKA phosphorylation needed for neuroP synthesis. Currently, it is not clear whether these developmental changes occur in existing astrocytes or are due to a new population of astrocytes born during puberty. However, strong evidence suggests that it is the former. Blocking new cell addition during puberty attenuates the LH surge. Together these results demonstrate the importance of pubertal maturation involving hypothalamic astrocytes, estradiol-induced neuroP synthesis and membrane-initiated progesterone signaling for the CNS control of ovulation and reproduction.

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

Cited by 35 publications

References 50 publications

PATL 2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice

PATL 2 is a key actor of oocyte maturation whose invalidation causes infertility in women and mice

Insulin Receptor Plasma Membrane Levels Increased by the Progesterone Receptor Membrane Component 1

Hypothalamic Astrocyte Development and Physiology for Neuroprogesterone Induction of the Luteinizing Hormone Surge

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