COVID-19 AFFECTS OVARIAN FUNCTION

HERRERO, YAMILA; NATALIA PASCUALI, CANDELA VELÁZQUEZ, GONZALO OUBIÑA, VANESA HAUK, IGNACIO DE ZÚÑIGA, MARIANA GÓMEZ PEÑA, GUSTAVO MARTÍNEZ, MARIANO LAVOLPE, FLORENCIA VEIGA, FERNANDO NEUSPILLER, DALHIA ABRAMOVICH; LEOPODINA SCOTTI; FERNANDA PARBORELL

Congreso; REUNIÓN CONJUNTA SAIC SAI AAFE NANOMED; 2021

SAIC

Coronavirus disease (COVID-19) is caused by the severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2). This virus invades the target cell by binding to angiotensinconverting enzyme 2 (ACE-2). In humans, ACE-2 was detected in uterus, vagina, placenta,and ovary. In the female gonad, both stromal and granulosa cells express ACE-2.During the final stages of folliculogenesis, the oocyte is exposed to a microenvironmentthat includes follicular fluid (FF) and somatic cells (the granulosa and theca cells) withinthe follicle.The composition of the FF reflects the stage of development of the oocytes and theirquality. Therefore, an altered FF composition is associated with reduced reproductivefunction.Our objective was to evaluate the effects of SARS-CoV-2 infection on ovarian function andconsequently on female fertility. To this purpose, the FF of the patients (n= 80; 21–41years old; November 2020-April 2021) were divided in two groups: FF of control patientsand FF of recovered COVID-19 patients.Levels of IgG antibodies against SARS-CoV-2 virus, levels of interleukin-1β (IL-1β),interleukin-10 (IL-10) and vascular endothelial growth factor (VEGF) were measured in FF.The expression of proteins related to stereidogenesis, VEGF and DNA damage marker(γH2AX) in granulosa cell cultures was also evaluated. On the other hand, in endothelialcells, migration, expression of angiogenic factors and DNA damage were analyzed.The results showed that 91.3% of the FF of the post-COVID-19 patients were positive forIgG against SARS-CoV-2. Patients with higher levels of SARS-CoV-2 IgG show a decrease inthe number of retrieved oocytes (p<0.05). The levels of VEGF and IL-1β were significantlylower(VEGF: p<0.05, IL-1β:p<0.0001) in post-COVID-19 FFs, while IL-10 did not differ fromthat of the control FFs.In human granulosa cells (COV434) stimulated with FF from post-COVID-19 patients, theexpression of the steroidogenic acute regulatory protein (StAR), estrogen receptor β (Erβ)and VEGF were significantly decreased (p<0.05), while the receptor of estrogens α (ERα)and 3β-hydroxysteroid dehydrogenase (3β-HSD) did not change.In human endothelial cells (EA.hy926) stimulated with post-COVID-19 FF, a decrease in cellmigration was observed (p<0.0001) without changes in the expression of angiogenesis-related proteins (Angiopoietin 1 and 2) compared to controls FF. Both cell types showedsignificantly higher expression of γH2AX when stimulated with post-COVID-19 FF (p < 0.05.We quantified proliferation using WST-1; no differences were found in COV434 andEA.hy926 cell proliferation rates between the groups.These results describe for the first time that SARS-CoV-2 infection alters the follicularmicroenvironment, damaging ovarian function, and potentially affecting reproductiveperformance in recovered COVID-19 patients. These results will provide more informationon the implementation / optimization of protocols in recovered COVID-19 patients whowish to have a child naturally or who require fertility treatments.