SARS-CoV-2 Infection of Human Ovarian Cells: A Potential Negative Impact on Female Fertility.

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.

Main actors behind the endometrial receptivity and successful implantation.

Embryo implantation occurs during a short period of time, the implantation window, in the mid-secretory phase of the menstrual cycle. The cross-talk between the endometrium and the embryo, at the stage of blastocyst, is a necessary condition for successful implantation. Till now, no single molecule or receptor has been identified to play an essential role on embryo implantation but a huge number of mediators, including cytokines, lipids, adhesion molecules, growth factors, and others, are reported to support the establishment of pregnancy. Therefore, the aim of this review is not only to describe the different actors involved in the implantation process, but also to try to characterize the relationships between these factors as well as their time-regulated activation. Moreover, the availability of in vitro culture systems to study the interactions between embryo and endometrium as well as the paracrine communication regulated by exosomal vesicles will be investigated, as an innovative approach for a more precise characterization of the interactions between the different molecules involved in this process. The in-depth knowledge of all these complex mechanisms will allow to address the reasons of implantation failure and infertility, thus providing new avenues for promoting the successful establishment of a pregnancy.