Laboratorio de Fisiopatología Ovárica, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU - CONICET Mendoza), Av. Ruiz Leal s/n Parque General San Martín, CP 5500, Mendoza, Argentina.
Facultad de Ingeniería y Facultad de Ciencias Médicas, Universidad de Mendoza, Mendoza, Argentina.
Sci Rep. 2024 Mar 16;14(1):6402. doi: 10.1038/s41598-024-57102-1.
Allopregnanolone (ALLO) is a known neurosteroid and a progesterone metabolite synthesized in the ovary, CNS, PNS, adrenals and placenta. Its role in the neuroendocrine control of ovarian physiology has been studied, but its in situ ovarian effects are still largely unknown. The aims of this work were to characterize the effects of intrabursal ALLO administration on different ovarian parameters, and the probable mechanism of action. ALLO administration increased serum progesterone concentration and ovarian 3β-HSD2 while decreasing 20α-HSD mRNA expression. ALLO increased the number of atretic follicles and the number of positive TUNEL granulosa and theca cells, while decreasing positive PCNA immunostaining. On the other hand, there was an increase in corpora lutea diameter and PCNA immunostaining, whereas the count of TUNEL-positive luteal cells decreased. Ovarian angiogenesis and the immunohistochemical expression of GABA receptor increased after ALLO treatment. To evaluate if the ovarian GABA receptor was involved in these effects, we conducted a functional experiment with a specific antagonist, bicuculline. The administration of bicuculline restored the number of atretic follicles and the diameter of corpora lutea to normal values. These results show the actions of ALLO on the ovarian physiology of the female rat during the follicular phase, some of them through the GABA receptor. Intrabursal ALLO administration alters several processes of the ovarian morpho-physiology of the female rat, related to fertility and oocyte quality.
别孕烯醇酮(ALLO)是一种已知的神经甾体,也是孕激素在卵巢、中枢神经系统、周围神经系统、肾上腺和胎盘内的代谢产物。它在卵巢生理学的神经内分泌控制中的作用已被研究,但它在卵巢中的局部作用在很大程度上仍然未知。本研究的目的是研究腔内 ALLO 给药对不同卵巢参数的影响及其可能的作用机制。ALLO 给药增加了血清孕激素浓度和卵巢 3β-HSD2,同时降低了 20α-HSD mRNA 的表达。ALLO 增加了闭锁卵泡的数量和 TUNEL 阳性颗粒细胞和膜细胞的数量,同时减少了 PCNA 免疫染色阳性的细胞数量。另一方面,黄体直径和 PCNA 免疫染色增加,而 TUNEL 阳性黄体细胞数量减少。卵巢血管生成和 GABA 受体的免疫组织化学表达在 ALLO 治疗后增加。为了评估卵巢 GABA 受体是否参与这些作用,我们进行了一项使用特异性拮抗剂,荷包牡丹碱的功能实验。荷包牡丹碱的给药将闭锁卵泡的数量和黄体直径恢复到正常水平。这些结果表明 ALLO 对雌性大鼠卵泡期卵巢生理学的作用,其中一些是通过 GABA 受体介导的。腔内 ALLO 给药改变了雌性大鼠卵巢形态生理学的几个过程,与生育力和卵母细胞质量有关。