PhD Student Universitat Autònoma de Barcelona Cerdanyola del vallès, Catalonia, Spain
Abstract Authors: Maria López-Panadés1,2; Ana Martínez-Marchal3; Cristina Madrid-Sandín1,2; Andros Maldonado-Linares1,2; Lluís Bassas4; Miguel Brieño-Enríquez3; Ignasi Roig 1,2*
1Unitat de Citologia i Histologia, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain
2Genome Integrity and Instability, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain
3Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, USA
4Laboratori de Seminologia i Embriologia, Servei d’Andrologia, Fundació Puigvert, Barcelona, Spain
*Corresponding author: Ignasi.Roig@uab.cat
Abstract Text: The SARS-CoV-2 virus has infected over 760 million people worldwide in the last three years and caused almost 7 million deaths. SARS-CoV-2 uses the TMPRSS2 protease and ACE2 receptor to infect host cells. Even though it is mainly a respiratory disease, both proteins are expressed in many tissues, including several testicular cell types. Abnormal levels of sex hormones and a decrease in sperm quality have been observed in patients during and after recovery from COVID-19. Furthermore, severe damage caused by inflammation has been detected in the testis of infected men. In addition, SARS-CoV-2 has been found in the testis. Thus, our objective was to explore the potential impact of COVID-19 on the male reproductive system. First, we analyzed the morphology of testis sections from patients deceased by COVID-19 and compared them to control samples of similar ages. Overall, COVID-19 samples displayed various anomalies commonly associated with compromised spermatogenesis, such as vacuolization of Sertoli cells, detachment of the germinal epithelium, or thickening of the basal lamina. Next, we studied the presence of different relevant biomarkers of spermatogenic cells, DNA damage, and leukocytes in these samples. A higher fraction of T lymphocytes and macrophages were detected in the peritubular spaces of COVID-19 samples compared to controls, thus confirming the infiltration of immune cells in the peritubular tissue of the testis. In addition, the seminiferous tubules of COVID-19 samples showed fewer UTF1-positive spermatogonia, which represents the spermatogonial stem cell population from which all sperm cells derive. Moreover, UTF1-positive spermatogonia presented more DNA damage than control cells, suggesting that COVID-19 could compromise spermatogenesis even after recovery. So, we conducted a study to examine the impact of SARS-CoV-2 infection on the testes of a small group of male individuals who had recovered from the virus infection. These patients also showed a decrease in the number of UTF1-positive spermatogonia, which presented more DNA damage, compared to controls. Finally, viral RNA was found in a fraction of COVID-19 necropsies. Nonetheless, more studies are needed to understand the impact of COVID-19 in spermatogenesis, especially in those patients that have recovered from the infection.
Financial Support Research was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (R00HD090289), Ferring COVID-19 Investigational Grant, MWRI Research and Education Funding and the Magee-Auxiliary Woman Scholar endowment (MARS), Ferring COVID-19 investigational grants in Reproductive Medicine and Maternal Health (FIN0045760) and Impact of COVID-19 on male reproductive Health - Fundació La Marató de TV3 (677/U/2021). MLP is a recipient from a fellowship from the AGAUR (2023 FISDU 00058).