Departments of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
PLoS One. 2013 Jun 20;8(6):e67068. doi: 10.1371/journal.pone.0067068. Print 2013.
The formation of primordial follicles involves the interaction between the oocytes and surrounding somatic cells, which differentiate into granulosa cells. Estradiol-17ß (E) promotes primordial follicle formation in vivo and in vitro; however, the underlying mechanisms are poorly understood. The expression of an ERBB3-binding protein 1 (EBP1) is downregulated in 8-day old hamster ovaries concurrent with the increase in serum estradiol levels and the formation of primordial follicles. The objectives of the present study were to determine the spatio-temporal expression and putative E regulation of EBP1 in ovarian cells during perinatal development with respect to primordial follicle formation. Hamster EBP1 nucleic acid and amino acid sequences were more than 93% and 98% similar, respectively, to those of mouse and human, and contained nucleolar localization signal, RNA-binding domain and several phosphorylation sites. EBP1 protein was present in somatic cells and oocytes from E15, and declined in oocytes by P1 and in somatic cells by P5. Thereafter, EBP1 expression increased through P7 with a transient decline on P8 primarily in interstitial cells. EBP1 mRNA levels mirrored protein expression pattern. E treatment on P1 and P4 upregulated EBP1 expression by P8 whereas E treatment on P4 downregulated it by 72 h suggesting a compensatory upregulation due to E pretreatment. Treatment with an FSH-antiserum, which suppressed primordial follicle formation, prevented the decline in EBP1 levels, and the effect was reversed by E treatment. Therefore, the results provide the first evidence that EBP1 may play an important role in mediating the effect of E in the differentiation of somatic cells into granulosa cells during primordial follicle formation.
原始卵泡的形成涉及卵母细胞和周围体细胞之间的相互作用,这些体细胞分化为颗粒细胞。雌二醇-17β(E)在体内和体外促进原始卵泡的形成;然而,其潜在机制尚不清楚。在与血清雌二醇水平升高和原始卵泡形成同时发生的情况下,ERBB3 结合蛋白 1(EBP1)的表达在 8 天大的仓鼠卵巢中下调。本研究的目的是确定 EBP1 在围产期卵巢细胞中的时空表达及其与原始卵泡形成的潜在 E 调节。仓鼠 EBP1 核酸和氨基酸序列与小鼠和人类的分别相似性超过 93%和 98%,并包含核仁定位信号、RNA 结合域和几个磷酸化位点。EBP1 蛋白存在于 E15 期的体细胞核卵母细胞中,并在 P1 期的卵母细胞中下降,在 P5 期的体细胞核卵母细胞中下降。此后,EBP1 表达通过 P7 增加,在 P8 期主要在间质细胞中短暂下降。EBP1 mRNA 水平与蛋白表达模式相匹配。E 在 P1 和 P4 处理上调 EBP1 表达至 P8,而 E 在 P4 处理下调至 72 小时,表明由于 E 预处理导致代偿性上调。用抑制原始卵泡形成的 FSH 抗血清处理可防止 EBP1 水平下降,并且 E 处理可逆转该作用。因此,结果首次提供了证据表明 EBP1 可能在介导 E 在原始卵泡形成过程中诱导体细胞核向颗粒细胞分化中的作用方面发挥重要作用。