Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, Oregon, 97006, USA.
Department of Reproductive Medicine, Tianjin Central Hospital of Gynecology Obstetrics, No 156 Nankai Sanma Road, Nankai District, Tianjin, 300100, China.
Sci Rep. 2018 Apr 18;8(1):6166. doi: 10.1038/s41598-018-24661-z.
Acetylcholine (ACh) in the ovary and its actions were linked to survival of human granulosa cells in vitro and improved fertility of rats in vivo. These effects were observed upon experimental blockage of the ACh-degrading enzyme (ACH esterase; ACHE), by Huperzine A. We now studied actions of Huperzine A in a three-dimensional culture of macaque follicles. Because a form of programmed necrotic cell death, necroptosis, was previously identified in human granulosa cells in vitro, we also studied actions of necrostatin-1 (necroptosis inhibitor). Blocking the breakdown of ACh by inhibiting ACHE, or interfering with necroptosis, did not improve the overall follicle survival, but promoted the growth of macaque follicles from the secondary to the small antral stage in vitro, which was correlated with oocyte development. The results from this translational model imply that ovarian function and fertility in primates may be improved by pharmacological interference with ACHE actions and necroptosis.
乙酰胆碱 (ACh) 在卵巢中的作用及其作用与体外培养的人颗粒细胞的存活和体内大鼠生育力的提高有关。这些作用是通过实验阻断乙酰胆碱降解酶 (ACH 酯酶；ACHE) ，即石杉碱甲观察到的。我们现在研究了石杉碱甲在猕猴卵泡三维培养中的作用。因为程序性坏死细胞死亡的一种形式，坏死性凋亡，以前在体外的人颗粒细胞中被鉴定，我们还研究了坏死性凋亡抑制剂 necrostatin-1 的作用。通过抑制 ACHE 抑制 ACh 的分解，或干扰坏死性凋亡，并没有提高卵泡的整体存活率，但促进了猕猴卵泡从次级到小腔卵泡的体外生长，这与卵母细胞的发育有关。该转化模型的结果表明，通过药理学干预 ACH 作用和坏死性凋亡，可能改善灵长类动物的卵巢功能和生育能力。
Zotero 插件
