Pgrmc1 Knockout Impairs Oocyte Maturation in Zebrafish.
Pgrmc1 Knockout Impairs Oocyte Maturation in Zebrafish.
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DOI：
10.3389/fendo.2018.00560
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发表时间：
2018
影响因子：
5.2
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Wu XJ;Thomas P;Zhu Y
最近的研究表明，孕激素受体膜组分1与广泛的分子如血红素、细胞色素P450、类固醇21碳、膜孕激素受体α(MPRα/Paqr7)、表皮生长因子受体(EGFR)和胰岛素受体结合并转运。用生化和药理学方法很难区分PGRMC1的真正功能和其相关分子的功能。为了确定PGRMC1的生理功能(S)，我们在斑马鱼中构建了PGRMC1(PGRMC1−/−)的全局基因敲除。我们发现雌性突变体的产卵频率和胚胎数量都减少了。我们还观察到在体内和体外，完全发育的未成熟卵母细胞对孕激素的敏感性降低，经历减数分裂成熟的卵母细胞数量减少。这种对孕激素敏感性的降低与mprα表达的显著降低很好地对应，mpr DNA是鱼类中主要负责介导卵母细胞成熟和减数分裂恢复的受体。这些结果为PgRMC1在卵母细胞成熟和受精过程中的生理功能提供了体内和体外证据，并提供了一种可能的分子机制，即通过调节MPRα，进而直接调节卵母细胞的成熟并影响斑马鱼的受精性。
Recent investigations suggest progestin receptor membrane component 1 (PGRMC1) associates with and transports a wide range of molecules such as heme, cytochromes P450, steroids with 21 carbons, membrane progestin receptor alpha (mPRα/Paqr7), epidermal growth factor receptor (EGFR), and insulin receptor. It is difficult to discriminate the true functions of PGRMC1 from the functions of its associated molecules using biochemical and pharmacological approaches. To determine the physiological function(s) of PGRMC1, we generated global knockouts for pgrmc1 (pgrmc1−/−) in zebrafish. We found a reduction in both spawning frequency and the number of embryos produced by female mutants. We also observed reduced sensitivity of fully-grown immature oocytes to a progestin hormone and a reduced number of oocytes undergone meiotic maturation both in vivo and in vitro in pgrmc1−/−. This reduced sensitivity to progestin corresponds well with significant reduced expression of mPRα, the receptor mainly responsible for mediating oocyte maturation and meiosis resumption in fish. The results provide in vivo and in vitro evidence for the physiological functions of Pgrmc1 in oocyte maturation and fertility, as well as a plausible molecular mechanism via regulation of mPRα, which in turn directly regulates oocyte maturation and affects fertility in zebrafish.
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影响因子：
4.1
作者：
Hardt, Robert;Winter, Dominic;Eckhardt, Matthias
通讯作者：
Eckhardt, Matthias
DOI：
10.1073/pnas.1601825113
发表时间：
2016-04-12
影响因子：
11.1
作者：
Kubota, Kaiyu;Cui, Wei;Soares, Michael J.
通讯作者：
Soares, Michael J.
影响因子：
16.6
作者：
Kabe Y;Nakane T;Koike I;Yamamoto T;Sugiura Y;Harada E;Sugase K;Shimamura T;Ohmura M;Muraoka K;Yamamoto A;Uchida T;Iwata S;Yamaguchi Y;Krayukhina E;Noda M;Handa H;Ishimori K;Uchiyama S;Kobayashi T;Suematsu M
通讯作者：
Suematsu M
影响因子：
29
作者：
Hughes, Adam L.;Powell, David W.;Espenshade, Peter J.
通讯作者：
Espenshade, Peter J.
DOI：
10.1073/pnas.1308335110
发表时间：
2013-08-20
影响因子：
11.1
作者：
Jao, Li-En;Wente, Susan R.;Chen, Wenbiao
通讯作者：
Chen, Wenbiao