SARS-CoV-2 infection negatively affects ovarian function in ART patients

Biochim Biophys Acta Mol Basis Dis. 2022 Jan 1;1868(1):166295. doi: 10.1016/j.bbadis.2021.166295. Epub 2021 Oct 27.


Several organs, such as the heart, breasts, intestine, testes, and ovaries, have been reported to be target tissues of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To date, no studies have demonstrated SARS-CoV-2 infection in the female reproductive system. In the present study, we investigated the effects of SARS-CoV-2 infection on ovarian function by comparing follicular fluid (FF) from control and recovered coronavirus disease 2019 (COVID-19) patients and by evaluating the influence of these FF on human endothelial and non-luteinized granulosa cell cultures. Our results showed that most FFs (91.3%) from screened post COVID-19 patients were positive for IgG antibodies against SARS-CoV-2. Additionally, patients with higher levels of IgG against SARS-CoV-2 had lower numbers of retrieved oocytes. While VEGF and IL-1β were significantly lower in post COVID-19 FF, IL-10 did not differ from that in control FF. Moreover, in COV434 cells stimulated with FF from post COVID-19 patients, steroidogenic acute regulatory protein (StAR), estrogen-receptor β (Erβ), and vascular endothelial growth factor (VEGF) expression were significantly decreased, whereas estrogen-receptor α (ERα) and 3β-hydroxysteroid dehydrogenase (3β-HSD) did not change. In endothelial cells stimulated with post COVID-19 FF, we observed a decrease in cell migration without changes in protein expression of certain angiogenic factors. Both cell types showed a significantly higher γH2AX expression when exposed to post COVID-19 FF. In conclusion, our results describe for the first time that the SARS-CoV-2 infection adversely affects the follicular microenvironment, thus dysregulating ovarian function.

Keywords: Angiogenesis; COVID-19; Follicular fluid; Retrieved oocytes; SARS-CoV-2 IgG antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / immunology
  • Biomarkers
  • COVID-19 / immunology
  • COVID-19 / metabolism*
  • COVID-19 / virology*
  • Cells, Cultured
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fertility
  • Follicular Fluid / metabolism
  • Granulosa Cells / metabolism
  • Host-Pathogen Interactions* / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Oocytes / metabolism
  • Ovary / metabolism*
  • Reproductive Techniques, Assisted*
  • SARS-CoV-2*
  • Young Adult


  • Antibodies, Viral
  • Biomarkers
  • Cytokines
  • Immunoglobulin G