Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia, USA.
Biol Reprod. 2023 Feb 13;108(2):258-268. doi: 10.1093/biolre/ioac189.
Angiogenesis within the ovarian follicle is an important component of ovulation. New capillary growth is initiated by the ovulatory surge of luteinizing hormone (LH), and angiogenesis is well underway at the time of follicle rupture. LH-stimulated follicular production of vascular growth factors has been shown to promote new capillary formation in the ovulatory follicle. The possibility that LH acts directly on ovarian endothelial cells to promote ovulatory angiogenesis has not been addressed. For these studies, ovaries containing ovulatory follicles were obtained from cynomolgus macaques and used for histological examination of ovarian vascular endothelial cells, and monkey ovarian microvascular endothelial cells (mOMECs) were enriched from ovulatory follicles for in vitro studies. mOMECs expressed LHCGR mRNA and protein, and immunostaining confirmed LHCGR protein in endothelial cells of ovulatory follicles in vivo. Human chorionic gonadotropin (hCG), a ligand for LHCGR, increased mOMEC proliferation, migration and capillary-like sprout formation in vitro. Treatment of mOMECs with hCG increased cAMP, a common intracellular signal generated by LHCGR activation. The cAMP analog dibutyryl cAMP increased mOMEC proliferation in the absence of hCG. Both the protein kinase A (PKA) inhibitor H89 and the phospholipase C (PLC) inhibitor U73122 blocked hCG-stimulated mOMEC proliferation, suggesting that multiple G-proteins may mediate LHCGR action. Human ovarian microvascular endothelial cells (hOMECs) enriched from ovarian aspirates obtained from healthy oocyte donors also expressed LHCGR. hOMECs also migrated and proliferated in response to hCG. Overall, these findings indicate that the LH surge may directly activate ovarian endothelial cells to stimulate angiogenesis of the ovulatory follicle.
卵泡内的血管生成是排卵的一个重要组成部分。新的毛细血管生长是由黄体生成素（LH）的排卵峰启动的，并且在卵泡破裂时血管生成已经进行得很好。已经表明，LH 刺激卵泡产生血管生长因子，促进排卵卵泡中新毛细血管的形成。LH 是否直接作用于卵巢内皮细胞以促进排卵血管生成的可能性尚未得到解决。对于这些研究，从食蟹猴中获得含有排卵卵泡的卵巢，并用于卵巢血管内皮细胞的组织学检查，并且从排卵卵泡中富集猴卵巢微血管内皮细胞（mOMEC）用于体外研究。mOMEC 表达 LHCGR mRNA 和蛋白，免疫染色证实了体内排卵卵泡内皮细胞中的 LHCGR 蛋白。人绒毛膜促性腺激素（hCG）是 LHCGR 的配体，增加了 mOMEC 的增殖、迁移和体外毛细血管样芽形成。用 hCG 处理 mOMEC 增加了 cAMP，这是 LHCGR 激活产生的常见细胞内信号。cAMP 类似物二丁酰基 cAMP 在没有 hCG 的情况下增加了 mOMEC 的增殖。蛋白激酶 A（PKA）抑制剂 H89 和磷脂酶 C（PLC）抑制剂 U73122 均阻断了 hCG 刺激的 mOMEC 增殖，表明多种 G 蛋白可能介导 LHCGR 作用。从健康卵母细胞供体获得的卵巢抽吸物中富集的人卵巢微血管内皮细胞（hOMEC）也表达 LHCGR。hOMEC 也响应 hCG 而迁移和增殖。总的来说，这些发现表明 LH 激增可能直接激活卵巢内皮细胞，刺激排卵卵泡的血管生成。
