Roberts Amanda E, Arbogast Laura K, Friedman Chad I, Cohn David E, Kaumaya Pravin T, Danforth Douglas R
Department of Animal Sciences, The Ohio State University, Columbus, Ohio 43210, USA.
Biol Reprod. 2007 Feb;76(2):218-23. doi: 10.1095/biolreprod.106.050880. Epub 2006 Oct 18.
The regulation of early follicular growth and development involves a complex interaction of autocrine, paracrine, and endocrine signals. The ability of these factors to regulate follicle growth may depend in part on the extent of vascular delivery to and perfusion of the ovary. Vascular endothelial growth factor A (VEGFA) is a major regulator of vascular physiology in the ovary. VEGFA is produced in numerous ovarian compartments and likely plays a role in the regulation of all phases of follicular growth, from preantral through preovulatory. The aim of the present study was to further evaluate the role of VEGF in early follicle growth by neutralization of endogenous VEGF or VEGF receptors. Adult mice were injected systemically and prepubertal mice were injected directly under the ovarian bursa with antibodies designed to neutralize VEGF or block interaction with its receptors in the ovary. Both systemic and intrabursal injections of VEGF antibody significantly reduced the number of primordial follicles within 1-3 days after administration without affecting primary or secondary follicle numbers. Primordial follicle numbers were not different from control levels by 30 days after VEGFA antibody administration. Administration of antibodies to the kinase domain receptor (KDR), but not the FMS-like tyrosine receptor (FLT1), for VEGF also resulted in a significant decrease in primordial follicles. These data suggest that VEGF plays a vital role in the maintenance and growth of the primordial follicle pool.
早期卵泡生长和发育的调节涉及自分泌、旁分泌和内分泌信号的复杂相互作用。这些因子调节卵泡生长的能力可能部分取决于卵巢的血管输送和灌注程度。血管内皮生长因子A（VEGFA）是卵巢血管生理学的主要调节因子。VEGFA在卵巢的多个区域产生，可能在卵泡生长的所有阶段（从窦前卵泡到排卵前卵泡）的调节中发挥作用。本研究的目的是通过中和内源性VEGF或VEGF受体来进一步评估VEGF在早期卵泡生长中的作用。成年小鼠进行全身注射，青春期前小鼠在卵巢囊下直接注射旨在中和VEGF或阻断其在卵巢中与受体相互作用的抗体。全身和囊内注射VEGF抗体均在给药后1 - 3天内显著减少了原始卵泡的数量，而不影响初级或次级卵泡的数量。给予VEGFA抗体30天后，原始卵泡数量与对照水平无差异。注射针对VEGF的激酶结构域受体（KDR）而非FMS样酪氨酸受体（FLT1）的抗体也导致原始卵泡显著减少。这些数据表明，VEGF在原始卵泡库的维持和生长中起着至关重要的作用。
