Nilsson Eric E, Detzel Chris, Skinner Michael K
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, 99164-4231, USA.
Reproduction. 2006 Jun;131(6):1007-15. doi: 10.1530/rep.1.00978.
Primordial follicles steadily leave the arrested pool and undergo a primordial to primary follicle transition during the female reproductive lifespan. When the available pool of primordial follicles is depleted reproduction ceases and humans enter menopause. The present study was designed to investigate the actions of several growth factors previously identified as candidate regulatory factors for the primordial to primary follicle transition with a microarray analysis. Ovaries from 4-day-old rats were placed into culture and treated for 2 weeks with platelet-derived growth factor (PDGF), anti-PDGF neutralizing antibody, vascular endothelial growth factor (VEGF), neuregulin (NRG), or kit ligand (KITL) as a positive control. PDGF-treatment resulted in a significant decrease in the percentage of primordial follicles and a concomitant increase in the percentage of developing primary follicles compared to controls. In contrast, ovaries treated with an anti-PDGF neutralizing antibody had a significant increase in the percentage of primordial follicles demonstrating an inhibition of endogenous follicle development. Ovaries incubated in the presence of VEGF or NRG had no change in follicle development. Observations indicate that PDGF, but not VEGF or NRG, promotes the primordial to primary follicle transition. Immunohistochemical localization indicated that the PDGF protein was present in the oocytes of both primordial and developing follicles. PDGF-treatment of cultured ovaries resulted in an increase in KITL mRNA expression. KITL has been previously shown to promote the primordial to primary follicle transition. KITL-treatment of ovaries had no effect on expression of Pdgf or any PDGF homologs or receptors. Therefore, PDGF appears to be produced by the oocyte and acts as one of several extracellular signaling factors that regulate the primordial to primary follicle transition. These observations provide insight into the cell-cell interactions involved in the regulation of primordial follicle development and can be used in the future development of therapies for some forms of infertility.
原始卵泡在雌性生殖寿命期间稳步离开静止库，并经历从原始卵泡到初级卵泡的转变。当可用的原始卵泡库耗尽时，生殖停止，人类进入更年期。本研究旨在通过微阵列分析研究几种先前被确定为原始卵泡到初级卵泡转变候选调节因子的生长因子的作用。将4日龄大鼠的卵巢置于培养中，并用血小板衍生生长因子（PDGF）、抗PDGF中和抗体、血管内皮生长因子（VEGF）、神经调节蛋白（NRG）或作为阳性对照的干细胞因子（KITL）处理2周。与对照组相比，PDGF处理导致原始卵泡百分比显著降低，同时发育中的初级卵泡百分比增加。相反，用抗PDGF中和抗体处理的卵巢原始卵泡百分比显著增加，表明内源性卵泡发育受到抑制。在VEGF或NRG存在下孵育的卵巢卵泡发育没有变化。观察结果表明，PDGF促进原始卵泡到初级卵泡的转变，而VEGF或NRG则无此作用。免疫组织化学定位表明，PDGF蛋白存在于原始卵泡和发育卵泡的卵母细胞中。对培养的卵巢进行PDGF处理导致KITL mRNA表达增加。先前已证明KITL可促进原始卵泡到初级卵泡的转变。对卵巢进行KITL处理对Pdgf或任何PDGF同源物或受体的表达没有影响。因此，PDGF似乎由卵母细胞产生，并作为调节原始卵泡到初级卵泡转变的几种细胞外信号因子之一发挥作用。这些观察结果为参与原始卵泡发育调节的细胞间相互作用提供了见解，并可用于未来某些形式不孕症治疗方法的开发。
