CDC42 controls the activation of primordial follicles by regulating PI3K signaling in mouse oocytes.
CDC42 controls the activation of primordial follicles by regulating PI3K signaling in mouse oocytes.
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CDC42通过调节小鼠卵母细胞中的PI3K信号传导来控制原始卵泡的激活
DOI：
10.1186/s12915-018-0541-4
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发表时间：
2018-07-05
期刊：
影响因子：
5.4
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Yan H;Zhang J;Wen J;Wang Y;Niu W;Teng Z;Zhao T;Dai Y;Zhang Y;Wang C;Qin Y;Xia G;Zhang H
研究背景哺乳动物雌性在成年期休眠的原始卵泡的逐渐激活对维持生殖寿命至关重要。原始卵泡激活失调导致各种卵巢疾病，如卵巢功能不全（POI）。虽然最近的研究表明，几个功能基因和途径，如磷酸肌醇3-激酶（PI 3 K）信号，发挥作用，在控制原始卵泡的激活，我们的理解的分子网络调节的激活progressions.ResultsHere，我们确定了一个新的作用细胞分裂周期42（CDC 42）在调节小鼠原始卵泡的激活。我们的研究结果表明，CDC 42的表达增加卵母细胞在卵巢原始卵泡的激活过程中。用特异性抑制剂破坏CDC 42的活性或敲低CDC 42的表达可显著抑制培养小鼠卵巢中原始卵泡的激活。相反，卵巢中过表达CDC 42可显著增加卵泡激活率。我们进一步证明了CDC 42通过与磷脂酰肌醇-4，5-二磷酸3-激酶催化亚基β（p110β）结合并调节卵母细胞中PTEN的表达水平来控制原始卵泡的激活过程。最后，我们将我们的研究扩展到潜在的临床应用，并表明短-结论在哺乳动物卵巢中，CDC 42调控着原始卵泡的激活，用特异性激活剂提高CDC 42的活性可能会提高原始卵泡的激活效率。体外激活方法，为不孕症治疗开辟了途径。
BackgroundIn mammalian females, progressive activation of dormant primordial follicles in adulthood is crucial for the maintenance of the reproductive lifespan. Misregulated activation of primordial follicles leads to various ovarian diseases, such as premature ovarian insufficiency (POI). Although recent studies have revealed that several functional genes and pathways, such as phosphoinositide 3-kinase (PI3K) signaling, play roles in controlling the activation of primordial follicles, our understanding of the molecular networks regulating the activation progress is still incomplete.ResultsHere, we identify a new role for cell division cycle 42 (CDC42) in regulating the activation of primordial follicles in mice. Our results show that CDC42 expression increases in oocytes during the activation of primordial follicles in the ovary. Disruption of CDC42 activity with specific inhibitors or knockdown ofCdc42expression significantly suppresses primordial follicle activation in cultured mouse ovaries. Conversely, the follicle activation ratio is remarkably increased by overexpression of CDC42 in ovaries. We further demonstrate that CDC42 governs the process of primordial follicle activation by binding to phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (p110β) and regulating the expression levels of PTEN in oocytes. Finally, we extend our study to potential clinical applications and show that a short-term in vitro treatment with CDC42 activators could significantly increase the activation rates of primordial follicles in both neonatal and adult mouse ovaries.ConclusionOur results reveal that CDC42 controls the activation of primordial follicles in the mammalian ovary and that increasing the activity of CDC42 with specific activators might improve the efficiency of in vitro activation approaches, opening avenues for infertility treatments.
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影响因子：
64.5
作者：
Fritsch R;de Krijger I;Fritsch K;George R;Reason B;Kumar MS;Diefenbacher M;Stamp G;Downward J
通讯作者：
Downward J
mTOR 和 PI3K 刺激剂体外激活原始卵泡的新策略
DOI：
10.1080/15384101.2014.995496
发表时间：
2015
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Sun X;Su Y;He Y;Zhang J;Liu W;Zhang H;Hou Z;Liu J;Li J
通讯作者：
Li J
影响因子：
5.3
作者：
MILLER, PJ;JOHNSON, DI
通讯作者：
JOHNSON, DI
DOI：
10.1530/jrf.0.0210081
发表时间：
1970-01-01
期刊：
JOURNAL OF REPRODUCTION AND FERTILITY
影响因子：
--
作者：
PEDERSEN, T
通讯作者：
PEDERSEN, T
影响因子：
56.9
作者：
Reddy, Pradeep;Liu, Lian;Liu, Kui
通讯作者：
Liu, Kui