The ovulatory up-regulation of ACE2, a receptor for SARS-COV-2, in dominant follicles of the human ovary.

Choi, Yohan; Jeon, Hayce; Brännström, Mats; Akin, James W.; Curry, Thomas E.; Jo, Misung

Objective To determine the temporal expression of ACE2, a receptor for SARS-COV-2, in dominant follicles across 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 IVF center. Patients Thirty premenopausal women undergoing surgery for tubal ligation and 16 premenopausal women undergoing IVF. Intervention (s) Administration of 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 Measures Expression and localization of ACE2 in granulosa cells and dominant follicles collected across the periovulatory period of the menstrual cycle and in hGLC using qPCR, immunoblotting, and immunohistochemistry. Results ACE2 expression (mRNA and protein) is up-regulated in human ovulatory follicles after hCG administration. ACE2 expression was higher in cumulus cells than granulosa cells. hCG increased the expression of ACE2 in primary hGLC cultures, but the increase was inhibited by both RU486 (an antagonist for progesterone receptor and glucocorticoid receptor) and CORT125281 (a selective glucocorticoid receptor), but not by AG1478 (an EGF-receptor tyrosine kinase inhibitor) or by dexamethasone. Conclusions The hormone-regulated expression of ACE2 in granulosa cells suggests a potential role of ACE2 in the ovulatory process. These data also implicate the possible impact of COVID-19 in a vital cyclic event of ovarian function, thus women's overall reproductive health. However, SAR-COV-2 infection in ovarian cells in vivo or in vitro has yet to be determined.