Is There a Role for SARS-CoV-2/COVID-19 on the Female Reproductive System?

Abstract

Coronavirus disease (COVID-19) has emerged as a very serious pandemic caused by the rapidly evolving transmission of the coronavirus SARS-CoV-2. Since its outbreak in 2020, the SARS CoV-2 has represented an important challenge for the physicians due to its well known respiratory sequelae. To date, the role of SARS-CoV-2 infection on organs and systems other than lungs and respiratory tract remains less clear. In particular, it remains to be investigated whether the reproductive system can be affected by the SARS-CoV-2 in the long term-period or, in alternative, drugs used to treat COVID-19 might impact the reproductive systems and, in turn, fertility. What is known is that SARS-Cov-2 binds to target cells of host through different receptors including angiotensin-converting enzyme 2 (ACE2), neuropilin-1, AXL and antibody-FcɣR complexes. ACE2 physiologically regulates both the expression of angiotensin II (Ang II) as well as Ang-(1-7) to exerts its physiological functions. The reproductive system abundantly expresses ACE2 and produces Ang-(1-7), starting from precursors which are locally generated or derived from systemic circulation. Ang-(1-7) plays an important role of stimulus to the growth and maturation of ovarian follicle as well as to ovulation. Also human endometrium expresses Ang-(1-7), mainly during the post-ovulatory phase. Animal and human observational studies demonstrated that Ang-(1-7) is involved in the maternal immune response to pregnancy and its deficiency is associated with a defective placenta development. In our manuscript, we review the current knowledge about whether SARS-CoV-2 may impact the female reproductive system. We further explain the possible molecular mechanism by which SARS-CoV-2 might affect ovarian, endometrial and female genital tract cells.

ACE inhibitors on ACE1, ACE2, and TMPRSS2 expression and spheroid attachment on human endometrial Ishikawa cells

“…In conclusion, the human endometrium expresses ACE1, ACE2, and TMPRSS2 transcripts and proteins. Similar findings have been reported in recent studies [35] , [36] , [37] . The commonly used human receptive endometrial Ishikawa and RL95–2 cells both express ACE1, ACE2, and TMPRSS2 transcripts and proteins making them suitable for in vitro studies on endometrial receptivity and embryo implantation.…”

SARS‐CoV‐2 infection and multi-organ system damage: a review

“…Ang (I-VII) is an essential stimulant for ovarian follicle development, maturation, and ovulation. Furthermore, the human endometrium expresses Ang (I-VII), mainly during the post-ovulatory phase [ 186 ]. Clarifying the effects of SARS-CoV-2 infection on human reproduction would thus give recommendations for women of reproductive age and provide a theoretical basis for the IVF and embryo transfer procedure.…”

“…Even though the newborn is not an organ of the mother, the newborn and the mother are an integral unit [ 187 ]. It has been reported that many factors contribute to ovary dysfunction during and after recovery from COVID-19 (immediate virus offensive, extreme immune response, and hypothalamus–pituitary–ovary axis dysfunction) [ 186 , 188 ]. Dysregulation of the adrenal gland and spermatogenesis in COVID-19 male patients have also been observed [ 179 , 185 ].…”

The potential effect of the COVID-19 pandemic on women’s reproductive health

“…У жіночих репродуктивних органах (яєчники, матка, піхва та плацента) було виявлено різний рівень експресії ACE2 і TMPRSS2. Крім того, ACE2 рясно експресується в яєчниках і ооцитах, особливо під час секреторної фази менструального циклу порівняно з проліферативною фазою [5,20]. Цілком можливо, що SARS-CoV-2 може націлитися на яєчники та ооцити, викликавши пряме ураження.…”