Objective

To determine the temporal expression of angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2, in dominant follicles throughout the periovulatory period in women and the regulatory mechanisms underlying ACE2 expression in human granulosa/lutein cells (hGLC).

Design

Experimental prospective clinical study and laboratory-based investigation.

Setting

University Medical Center and private in vitro fertilization center.

Patient(s)

Thirty premenopausal women undergoing surgery for tubal ligation and 16 premenopausal women undergoing in vitro fertilization.

Intervention(s)

Administration of human chorionic gonadotropin (hCG) and harvesting of preovulatory/ovulatory follicles by timed laparoscopy, and collection of granulosa/lutein cells and cumulus cells at the time of oocyte retrieval.

Main Outcome Measure(s)

Expression and localization of ACE2 in granulosa cells and dominant follicles collected throughout the periovulatory period of the menstrual cycle and in hGLC using quantitative polymerase chain reaction, immunoblotting, and immunohistochemistry.

Result(s)

ACE2 expression (mRNA and protein) is up-regulated in human ovulatory follicles after administration of hCG. ACE2 expression was higher in cumulus cells than in granulosa cells. hCG increased the expression of ACE2 in primary hGLC cultures; the increase was inhibited by RU486 (an antagonist for progesterone receptor and glucocorticoid receptor) and CORT125281 (a selective glucocorticoid receptor antagonist), but not by AG1478 (an EGF receptor tyrosine kinase inhibitor) or by dexamethasone.

Conclusion(s)

The hormone-regulated expression of ACE2 in granulosa cells suggests a potential role of ACE2 in the ovulatory process. These data also imply the possible impact of COVID-19 on a vital cyclic event of ovarian function and thus on women's overall reproductive health. However, SAR-CoV-2 infection in ovarian cells in vivo or in vitro has yet to be determined.

中文翻译：

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人卵巢优势卵泡中血管紧张素转换酶 2（SARS-CoV-2 的一种受体）的排卵上调

 客观的

旨在确定女性整个排卵期优势卵泡中血管紧张素转换酶 2 (ACE2)（SARS-CoV-2 的一种受体）的时间表达，以及人颗粒/叶黄素细胞 (hGLC) 中ACE2表达的调节机制。

 设计

实验性前瞻性临床研究和基于实验室的调查。

 环境

大学医学中心和私人体外受精中心。

 患者）

30 名绝经前妇女接受输卵管结扎手术，16 名绝经前妇女接受体外受精。

 干预措施

施用人绒毛膜促性腺激素 (hCG) 并通过定时腹腔镜检查收获排卵前/排卵卵泡，并在卵母细胞取出时收集颗粒/叶黄素细胞和卵丘细胞。

 主要观察指标）

使用定量聚合酶链反应、免疫印迹和免疫组织化学，在整个月经周期的排卵期和 hGLC 中收集颗粒细胞和优势卵泡中 ACE2 的表达和定位。

 结果）

施用 hCG 后，人排卵卵泡中ACE2表达（mRNA 和蛋白质）上调。卵丘细胞中的ACE2表达高于颗粒细胞。 hCG 增加原代 hGLC 培养物中ACE2的表达；这种增加被RU486（一种黄体酮受体和糖皮质激素受体拮抗剂）和CORT125281（一种选择性糖皮质激素受体拮抗剂）抑制，但不被AG1478（一种EGF受体酪氨酸激酶抑制剂）或地塞米松抑制。

 结论

颗粒细胞中ACE2的激素调节表达表明 ACE2 在排卵过程中的潜在作用。这些数据还表明，COVID-19 对卵巢功能的重要周期性事件可能产生影响，从而对女性的整体生殖健康产生影响。然而，SAR-CoV-2在体内或体外感染卵巢细胞的情况尚未确定。