SARS-CoV-2 Infection of Human Ovarian Cells: A Potential Negative Impact on Female Fertility.
Francesca Paola LuongoFilippo DragoniAdele BoccutoEugenio PaccagniniMariangela GentileTamara CanosiGiuseppe MorganteAlice LuddiMaurizio ZazziIlaria VicentiPaola PiomboniPublished in: Cells (2022)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect female reproductive health. Here, we investigated the potential of SARS-CoV-2 to infect the follicular microenvironment, in particular granulosa (GCs) and cumulus cells (CCs), thus providing evidence for a productive infection. GCs and CCs were recovered from women (n = 25) who underwent in vitro fertilization at the Assisted Reproductive Unit, Siena University Hospital. Follicular ovarian cells were co-cultured with SARS-CoV-2 and then analyzed by qPCR, immunofluorescence (IF), western blot (WB) and transmission electron microscopy (TEM). In addition, cell culture supernatant was used to infect VERO6 cells. We demonstrated the expression of cell host factors ACE2, TRPMSS2, BSG and CTSL, which are pivotal for the virus life cycle. Cultured GCs and CCs incubated with SARS-CoV-2 revealed productive SARS-CoV-2 infection at 24 h, 48 h and 72 h post-adsorption. Indeed, SARS-CoV-2 RNA, spike and nucleocapsid proteins were detected in GCs and CCs, and their cell culture supernatant successfully infected the standard VERO E6 cells. Finally, TEM showed full-size virions attached to the membrane and located inside the cytoplasm. This in vitro study reveals the susceptibility of human ovarian cells to SARS-CoV-2 infection, suggesting a potential detrimental effect of COVID-19 infection on female human fertility.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- induced apoptosis
- cell cycle arrest
- endothelial cells
- endoplasmic reticulum stress
- oxidative stress
- coronavirus disease
- cell death
- stem cells
- polycystic ovary syndrome
- type diabetes
- pregnant women
- mass spectrometry
- mesenchymal stem cells
- south africa
- cell proliferation
- single cell
- human health