COVID-19 Infections in Gonads: Consequences on Fertility?

Abstract

COVID-19 may influence human fertility and sexuality in several ways. Different cell types in gonads show a constitutive expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), which provide potential entry pathways for SARS-CoV-2. In addition to the biological effects of a COVID-19 infection on the gonads, the impact of the ongoing COVID-19 pandemic on mental health issues and sexual behavior may affect reproduction. This review summarizes the current knowledge on the influence of COVID-19 on the gonads and discusses possible consequences on human fertility. In this context, the close interaction between the hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-gonadal axis in response to COVID-19-related stress is discussed. Some women noticed changes in their menstrual cycle during the COVID-19 pandemic, which could be due to psychological stress, for example. In addition, occasional cases of reduced oocyte quality and ovarian function are described after COVID-19 infection. In men, COVID-19 may cause a short-term decrease in fertility by damaging testicular tissue and/or impairing spermatogenesis. Moreover, decreased ratio testosterone/LH and FSH/LH in COVID-19 compared to aged-matched healthy men has been reported. Available data do not suggest any effect of the available SARS-CoV-2 vaccines on fertility. The effects of long COVID on human fertility have been reported and include cases with premature ovarian failure and oligomenorrhoea in women and erectile dysfunction in men. Despite the increasing knowledge about the effects of COVID-19 infections on human gonads and fertility, the long-term consequences of the COVID-19 pandemic cannot yet be assessed in this context.

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

“…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 ].…”

SARS-CoV-2 infection and its effects on the endocrine system

“…The abundant expression of ACE2 is correlated with the generation of angiotensin 1–7, which stimulates ovarian follicle growth, oocyte maturation and ovulation [23] . ACE2 expression appears to be lower in the human ovaries than in the testis [44] , which may indicate a higher susceptibility of male gonads for SARS-CoV-2 than female gonads.…”

“…The testis has a high constitutive expression of ACE2 due to RAAS functions in Leydig cells [42] , [43] . ACE2 and TMPRSS2 are mainly expressed in spermatocytes, spermatids, Sertoli cells, testicular tubuli and interstitium [44] , [45] . Testicular mRNA levels of ACE2 and TMPRSS2 are shown to be increased in COVID-19 patients [45] .…”

“…This is most likely not due to the actual infection but rather psychological stress [93] . On the other hand, occasional cases of reduced oocyte quality and ovarian function were reported [44] . In men, COVID-19 may cause a short-term decrease in fertility due to damaged testicular tissue and/or impaired spermatogenesis [94] .…”

The Role of Endocrine and Metabolic System in COVID-19 Disease – The Transcampus Experience and Review of Evidence From International Collaborating Groups

“…Tsourdi et al [7] summarize the evidence from preclinical models and clinical studies about the effects of COVID-19 and its treatments on bone metabolism and they discuss how osteoporosis medications may have beneficial effects on the clinical course of COVID-19. Bechmann et al [8] present the effects of COVID-19 on gonads and how biological factors, mental health issues and sexual behavior may alter reproductive function and human fertility. Finally, Kurtulmus et al report six cases of subacute thyroiditis following vaccination against SARS-Cov-2 and discuss the possible mechanisms of vaccine-induced thyroiditis [9].…”