Regulation of ovarian primordial follicle assembly and development by estrogen and progesterone: Endocrine model of follicle assembly
Regulation of ovarian primordial follicle assembly and development by estrogen and progesterone: Endocrine model of follicle assembly
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DOI：
10.1210/en.2002-0131
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发表时间：
2003-08-01
期刊：
影响因子：
4.8
通讯作者：
Skinner, MK
中科院分区：
文献类型：
--
作者：
Kezele, P;Skinner, MK
发育停滞的原始卵泡的组装和随后的原始卵泡向初级卵泡的过渡是正常卵巢生理学中的关键过程，仍有待阐明。卵巢卵泡不增殖，新生儿中存在的原始卵泡代表了女性在整个生殖生命中可获得的配子总数。原始卵泡是由分化较低的鳞状颗粒细胞包围的卵母细胞，并且来自卵母细胞巢，初级卵泡是由单层立方颗粒细胞包围的卵母细胞，其已经启动卵泡发育。原始卵泡组装、停滞和发育（即原始卵泡向初级卵泡转变）的异常可导致病理状况，如卵巢早衰。本研究采用新生大鼠卵巢培养7 d。原始卵泡在体内的组装率与体外组装率基本一致。有趣的是，在培养中发现原始卵泡向初级卵泡转变的速率是3倍。培养中初级卵泡发育的异常率表明原始卵泡在体内发育中并不停滞。为了研究这一现象，新生大鼠卵巢培养在孕酮，雌二醇或小牛血清的存在下。雌二醇、孕酮或小牛血清显著降低了原始卵泡向初级卵泡转变的水平。在对照卵巢中，约60%的卵泡发生原始卵泡向初级卵泡的转变，在治疗卵巢中约30%。类固醇和小牛血清对从出生后4-d龄大鼠收集和培养的卵巢中的原始卵泡向初级卵泡转变没有影响，这表明观察到的影响仅限于原始卵泡向初级卵泡转变的初始波。有趣的是，孕酮也被发现显着降低原始卵泡组装的速度。在对照组卵巢中，所有活卵母细胞组装成原始卵泡，在炔雌醇处理的卵巢中，约40%的卵母细胞未组装。还发现孕酮减少体内原始卵泡组装，在注射孕酮的新生动物中有10%的卵泡未组装。细胞凋亡分析表明，孕激素抑制原始卵泡组装所需的卵母细胞协调凋亡。提出的假设是，母体和胎儿体内高水平的类固醇阻止了胚胎中原始卵泡的过早组装和原始卵泡向初级卵泡的转变。出生后，类固醇水平急剧下降，原始卵泡可以自由组装并开始发育。这些观察结果表明，类固醇和母胎内分泌单位在控制卵巢原始卵泡组装和早期卵泡发育中的新作用。
The assembly of the developmentally arrested primordial follicle and the subsequent transition of the primordial follicle to the primary follicle are critical processes in normal ovarian physiology that remain to be elucidated. Ovarian follicles do not proliferate and the primordial follicles present in the neonate represent the total number of gametes available to a female throughout her reproductive life. The primordial follicles are oocytes surrounded by less differentiated squamous granulosa cells and are derived from oocyte nests, and primary follicles are oocytes surrounded by a single layer of cuboidal granulosa cells that have initiated follicle development. Abnormalities in primordial follicle assembly, arrest, and development (i.e. primordial to primary follicle transition) can cause pathological conditions such as premature ovarian failure. In this study newborn rat ovaries were cultured for 7 d. The rate of primordial follicle assembly in vivo was identical with the rate in vitro. Interestingly, the rate of primordial follicle transition to the primary follicle was found to be 3 times greater in culture. This abnormal rate of primary follicle development in culture suggests the primordial follicle does not arrest in development as observed in vivo. To investigate this phenomena newborn rat ovaries were cultured in the presence of progesterone, estradiol or calf serum. Estradiol, progesterone, or calf serum significantly reduced the level of initial primordial to primary follicle transition. Approximately 60% of follicles make the primordial to primary follicle transition in control ovaries and about 30% in treated ovaries. Steroids and calf serum had no effect on the primordial to primary follicle transition in ovaries collected and cultured from postnatal 4-d-old rats, suggesting the effects observed are restricted to the initial wave of primordial to primary follicle transition. Interestingly, progesterone was also found to significantly reduce the rate of primordial follicle assembly. All viable oocytes assembled into primordial follicles in control ovaries and approximately 40% remained unassembled in progesterone-treated ovaries. Progesterone was also found to reduce primordial follicle assembly in vivo with 10% of the total follicles remaining unassembled in progesterone injected neonatal animals. Analysis of cellular apoptosis demonstrated that progesterone inhibited the coordinated oocyte apoptosis required for primordial follicle assembly. The hypothesis developed is that high levels of maternal and fetal steroids prevent premature primordial follicle assembly and primordial to primary follicle transition in the embryo. After birth steroid levels fall dramatically and the primordial follicles are free to assemble and initiate development. These observations suggest a novel role for steroids and the maternal-fetal endocrine unit in the control of ovarian primordial follicle assembly and early follicular development.