During follicular development, a few dominant follicles develop to large antral dominant follicles, whereas the remaining follicles undergo atretic degeneration. Because vascularization on the follicular surface is a morphological feature of dominant follicles, we previously classified these follicles as vascularized follicles (VFs) and non-VFs (NVFs). In NVFs, progesterone producing genes were expressed similarly to that in VFs; however, the progesterone concentration in follicular fluid was low in large NVFs. Therefore, we estimated that progesterone is converted to cortisol, which induces the loss of follicular functions. In this study, we comparative analyzed the expression of genes for progesterone converting enzymes (Cytochrome (CYP)11B1, CYP21A2, Hydroxysteroid (HSD)11B2) and cortisol receptor (NR3C1) in VF and NVF granulosa cells. In NVFs, expression of cortisol producing genes (CYP11B1 and CYP21A2) was higher than in VFs. Expression of the gene for the cortisol metabolizing enzyme HSD11B2 in NVFs was significantly lower than in VFs. In NVFs, accompanied by increasing cortisol concentration in follicular fluid, apoptosis of granulosa and cumulus cells was observed. Cultivation with FSH and metyrapone (a CYP11B1 inhibitor) of NVF cumulus–oocyte complexes inhibited apoptosis of cumulus cells and induced cumulus cell proliferation and oocyte maturation. Cortisol-induced CYP11B1 and CYP21A2 expression, whereas FSH-induced HSD11B2 mRNA expression in VF granulosa cells in the presence of cortisol. Furthermore, an addition of 18β-glycyrrhetinic acid (18-GA; a HSD17B2 inhibitor) to cortisol and FSH-containing medium increased apoptosis of VF granulosa cells. These results suggested that cortisol is a stimulatory factor that induces follicular atresia; furthermore, inhibition of cortisol production by FSH might increase the number of healthy preovulatory follicles in pigs.

中文翻译：

---

皮质醇诱导卵泡退化，而 FSH 阻止皮质醇诱导的猪卵泡退化

在卵泡发育过程中，少数优势卵泡发育为大的窦状优势卵泡，而其余卵泡则发生闭锁变性。因为卵泡表面的血管化是优势卵泡的形态特征，我们之前将这些卵泡分类为血管化卵泡 (VFs) 和非 VFs (NVFs)。在 NVFs 中，产生孕酮的基因与 VFs 中的表达相似。然而，大型 NVF 中卵泡液中的孕酮浓度较低。因此，我们估计黄体酮会转化为皮质醇，从而导致卵泡功能丧失。在这项研究中，我们比较分析了 VF 和 NVF 颗粒细胞中孕酮转化酶（细胞色素 (CYP)11B1、CYP21A2、羟基类固醇 (HSD)11B2）和皮质醇受体 (NR3C1) 基因的表达。在 NVF 中，皮质醇产生基因（CYP11B1 和 CYP21A2）的表达高于 VF。NVFs中皮质醇代谢酶HSD11B2基因的表达明显低于VFs。在NVFs中，伴随着卵泡液中皮质醇浓度的增加，颗粒细胞和卵丘细胞出现凋亡。用 FSH 和美替拉酮（一种 CYP11B1 抑制剂）培养 NVF 卵丘-卵母细胞复合物可抑制卵丘细胞凋亡并诱导卵丘细胞增殖和卵母细胞成熟。在皮质醇存在的情况下，皮质醇诱导 CYP11B1 和 CYP21A2 表达，而 FSH 诱导 VF 颗粒细胞中 HSD11B2 mRNA 表达。此外，在含有皮质醇和 FSH 的培养基中添加 18β-甘草次酸（18-GA；一种 HSD17B2 抑制剂）可增加 VF 颗粒细胞的凋亡。这些结果表明，皮质醇是诱发毛囊闭锁的刺激因子；此外，FSH 抑制皮质醇的产生可能会增加猪体内健康排卵前卵泡的数量。