Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Cellular and Integrative Physiology, and University of Nebraska Medical Center, Omaha, NE, USA.
Sci Rep. 2017 Nov 14;7(1):15581. doi: 10.1038/s41598-017-15833-4.
Primordial follicle (PF) pool determines the availability of follicles for ovulation in all mammals. Premature depletion of the PF reserve leads to subfertility or infertility. Bone morphogenetic protein 2 (BMP2) promotes PF formation by facilitating oocyte and granulosa cell development. Estradiol-17β (E2) upregulates PF formation in developing hamster ovaries. However, if BMP2 mediates E2 effect is not known. We hypothesize that E2 facilitates the effect of BMP2 on somatic to granulosa cell transition. BMP2 and E2 together significantly upregulated the percentage of PFs in hamster fetal ovaries in vitro compared with either of the treatments alone. E2 also promoted BMP2 expression in vivo. Inhibition of BMP2 receptors suppressed E2-stimulation of PF formation while knockdown of BMP2 in vitro significantly suppressed the E2 effect. In contrast, estrogen receptor blocker did not affect BMP2 action. Inhibition of the activity of E2 or BMP2 receptors, either alone or combined during the last two days of the culture (C6-C8) resulted in a significant decrease in PF formation by C8, suggesting that both BMP2 and E2 action is essential for somatic cell differentiation for PF formation. Together, the results suggest that E2 activates BMP2-BMPR system leading to the formation of primordial follicles.
原始卵泡 (PF) 池决定了所有哺乳动物排卵时卵泡的可用性。PF 储备过早耗竭会导致生育力下降或不孕。骨形态发生蛋白 2 (BMP2) 通过促进卵母细胞和颗粒细胞的发育来促进 PF 的形成。雌二醇-17β (E2) 上调发育中的仓鼠卵巢中 PF 的形成。然而，BMP2 是否介导 E2 效应尚不清楚。我们假设 E2 促进了 BMP2 对体细胞向颗粒细胞转化的作用。BMP2 和 E2 一起显著上调了体外仓鼠胎儿卵巢中 PF 的比例，与单独使用任何一种处理相比。E2 还促进了体内 BMP2 的表达。BMP2 受体抑制剂抑制了 E2 对 PF 形成的刺激，而体外 BMP2 的敲低显著抑制了 E2 的作用。相比之下，雌激素受体阻滞剂不影响 BMP2 的作用。在培养的最后两天 (C6-C8) 中单独或联合抑制 E2 或 BMP2 受体的活性，导致 C8 中 PF 形成显著减少，这表明 BMP2 和 E2 均对体细胞分化形成 PF 至关重要。综上所述，这些结果表明 E2 激活了 BMP2-BMPR 系统，导致原始卵泡的形成。
