Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Oregon Health & Science University, OR, USA.
Department of Obstetrics and Gynecology, School of Medicine, Oregon Health & Science University, OR, USA.
Biol Reprod. 2021 Mar 11;104(3):602-610. doi: 10.1093/biolre/ioaa227.
Insulin-like growth factors (IGFs) are known for their involvement in endocrine and paracrine regulation of ovarian function. Although IGF2 is the predominant circulating and intraovarian form of IGFs in primate species, the stage-specific follicular expression, action, and regulation of IGF2 are not well defined. Therefore, experiments were conducted to investigate the follicular IGF production in response to steroid hormone regulation and the direct IGF actions on follicular development and function in vitro. Preantral follicles were isolated from rhesus macaque ovaries and cultured to the antral stage in media supplemented with follicle-stimulating hormone and insulin. Follicles were randomly assigned to treatment groups: (a) control, (b) trilostane (a steroid synthesis inhibitor), (c) trilostane + estradiol, (d) trilostane + progesterone, and (e) trilostane + dihydrotestosterone. Media was analyzed for IGF concentrations, which were correlated to follicle growth. Follicles produced IGF2, but not IGF1, at the antral stage. Steroid depletion decreased, whereas steroid replacement increased, IGF2 production by antral follicles. Media IGF2 levels correlated positively with antral follicle diameters. Macaque preantral follicles and granulosa cells were subsequently cultured without (control) and with recombinant human IGF2 supplementation. Follicle survival, growth, and paracrine factor production, as well as granulosa cell proliferation and gonadotropin receptor gene expression, were assessed. IGF2 addition increased follicle survival rates, diameters and inhibin B production, as well as granulosa cell proliferation. These data demonstrate that IGF2 produced by antral follicles, in response to steroid hormone regulation, could act as a paracrine factor that positively impacts preantral follicle development and function in primates.
胰岛素样生长因子 (IGFs) 以其在内分泌和旁分泌调节卵巢功能中的作用而闻名。虽然 IGF2 是灵长类动物中主要的循环和卵巢内 IGF 形式，但 IGF2 的卵泡特异性表达、作用和调节尚不清楚。因此，进行了实验以研究卵泡对甾体激素调节的 IGF 产生以及 IGF 对体外卵泡发育和功能的直接作用。从恒河猴卵巢中分离出原始卵泡，并在添加卵泡刺激素和胰岛素的培养基中培养至腔前卵泡阶段。卵泡被随机分配到以下治疗组：(a) 对照组，(b) 三氯生（一种甾体合成抑制剂），(c) 三氯生+雌二醇，(d) 三氯生+孕酮，和 (e) 三氯生+二氢睾酮。分析培养基中的 IGF 浓度，与卵泡生长相关。腔前卵泡阶段产生 IGF2，但不产生 IGF1。甾体耗竭减少，而甾体替代增加，腔前卵泡产生 IGF2。培养基 IGF2 水平与腔前卵泡直径呈正相关。随后，猕猴原始卵泡和颗粒细胞在没有（对照）和添加重组人 IGF2 的情况下进行培养。评估卵泡存活、生长和旁分泌因子产生以及颗粒细胞增殖和促性腺激素受体基因表达。IGF2 增加了卵泡存活率、直径和抑制素 B 产生以及颗粒细胞增殖。这些数据表明，腔前卵泡对甾体激素调节产生的 IGF2 可以作为旁分泌因子，对灵长类动物的原始卵泡发育和功能产生积极影响。
