IL-1 also induces the secretion of TNF and directly raises vascular permeability(50)and, in turn, TNF enhances new blood vessel growth during inflammatory processes(51)

IL-1 also induces the secretion of TNF and directly raises vascular permeability(50)and, in turn, TNF enhances new blood vessel growth during inflammatory processes(51). COVID-19 individuals, steroidogenic acute regulatory protein (Celebrity), estrogen-receptor (Er), and vascular endothelial growth factor (VEGF) manifestation were significantly decreased, whereas estrogen-receptor (ER) and 3-hydroxysteroid dehydrogenase (3-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 H2AX expression when exposed to post COVID-19 FF. In conclusion, our results describe for the first time that this SARS-CoV-2 contamination adversely affects the follicular microenvironment, thus dysregulating ovarian function. Keywords:COVID-19, SARS-CoV-2 IgG antibodies, Follicular fluid, F-TCF Retrieved oocytes, Angiogenesis == 1. Introduction == Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world. As of June 14, 2021, more than 175 million cases and 3.7 million deaths are attributed to this virus worldwide. In Argentina, around 3.48 million cases were confirmed with 73,391 reported deaths[1],[2]. SARS-CoV-2 invades the Fexinidazole target cell by binding to angiotensin-converting enzyme 2 (ACE-2). The viral access is further processed by the transmembrane serine protease 2 (TMPRSS2), thus allowing the fusion of the cell membranes of Fexinidazole computer virus and host cell(3). It is public knowledge that SARS-CoV-2 can cause severe damage, particularly in the respiratory system(4). The most frequently observed symptoms in COVID-19 patients include fever, cough, and pneumonia. However, other symptoms such as thrombosis, pulmonary embolism, and high blood pressure have been reported as well, suggesting that this computer virus targets the endothelium[5],[6]. It is well known that ACE-2 is also expressed in endothelial cells[7],[8]. Additionally, dysregulated immune responses, as those observed in COVID-19, are a major culprit in endothelial dysfunction, since they alter microvascular permeability and induce vascular inflammation(6). Nonetheless, other Fexinidazole organs such as the heart, breasts, intestine, testes, and ovaries have also been reported to be target tissues of this viral contamination[9],[10].To date, no studies have presented evidence of SARS-CoV-2 infecting the female reproductive system. ACE-2 is expressed in the uterus, vagina, placenta, and ovary[11],[12]. In particular, ACE-2 mRNA transcripts have been detected in ovaries from reproductive-age and postmenopausal women. Both stromal and granulosa cells have been found to be positive for ACE-2 in the human ovary(13). Furthermore, ACE-2 expression in rat and bovine granulosa cells is usually regulated by gonadotropic hormones[14],[15]. Whether this computer virus binds to ACE-2 receptors in the ovary and which effects, if any, this contamination would have on ovarian function and oocyte quality remains unclear. Nevertheless, to the best of our knowledge, no reports have addressed the consequences of COVID-19 on ovarian function. During the final stages of folliculogenesis, the oocyte is usually localized in an antral follicle in the ovary. The female gamete is exposed to a microenvironment that includes follicular fluid (FF) and somatic cells (namely granulosa and theca cells) within the follicle. The composition of FF Fexinidazole differs from that of serumit is usually a complex mixture of hormones, cytokines, metabolites, and other proteins secreted mainly by granulosa cells[16],[17]. FF composition displays the stage of oocyte development and oocyte quality[18],[19]. Therefore, an altered FF composition is associated with a reduced reproductive function. Based on these considerations, we hypothesized that this SARS-CoV-2 contamination can potentially impact ovarian function, disturbing the follicular microenvironment and thus affecting oocyte quality in recovered women. Hence, we evaluated the presence of SARS-CoV-2 IgG antibodies and antigens, interleukin-1 (IL-1), interleukin-10 (IL-10), and vascular endothelial growth Fexinidazole factor (VEGF) levels in FF from healthy and recovered SARS-CoV-2 women undergoing assisted reproductive technology (ART) procedures. We also examined the effect of FFs obtained from the above-mentioned patients on: a) the proliferation, migration, angiopoietins 1 and 2 (ANGPT-1/2), and VEGF expression of a human endothelial cell culture; and b) the proliferation and protein expression of estrogen-receptor (ER) and (ER), steroidogenic acute.