SARS-CoV-2 Nucleocapsid Protein is Associated With Lower Testosterone Levels: An Experimental Study

Caio Henrique Lucio Carrasco; Paloma Noda; Ana Paula Barbosa; Everidiene Kinverlly Vieira Borges da Silva; Camila Gasque Bomfim; Bianca Helena Ventura Fernandes; Thiago Afonso Teixeira; Amaro Nunes Duarte Neto; Paulo Hilario Nascimento Saldiva; Kamal Achoa Filho; Cristiane Rodrigues Guzzo; Edison Luiz Durigon; Fernando Luiz Affonso Fonseca; Roseli Corazzini; Camilla Fanelli; Irene Lourdes Noronha; Jorge Hallak

doi:10.3389/fphys.2022.867444

SARS-CoV-2 Nucleocapsid Protein is Associated With Lower Testosterone Levels: An Experimental Study

Front Physiol. 2022 Jun 3:13:867444. doi: 10.3389/fphys.2022.867444. eCollection 2022.

Authors

Caio Henrique Lucio Carrasco^{1

2}, Paloma Noda³, Ana Paula Barbosa⁴, Everidiene Kinverlly Vieira Borges da Silva³, Camila Gasque Bomfim⁴, Bianca Helena Ventura Fernandes⁴, Thiago Afonso Teixeira^{1

2}, Amaro Nunes Duarte Neto⁵, Paulo Hilario Nascimento Saldiva^{5

6}, Kamal Achoa Filho³, Cristiane Rodrigues Guzzo⁴, Edison Luiz Durigon⁴, Fernando Luiz Affonso Fonseca⁷, Roseli Corazzini⁷, Camilla Fanelli³, Irene Lourdes Noronha³, Jorge Hallak^{1

2

5

6}

Affiliations

¹ Androscience-Science and Innovation Center in Andrology and High-Complex Clinical and Research Andrology Laboratory, Sao Paulo, Brazil.
² Division of Urology, Hospital Das Clinicas, University of Sao Paulo Medical School, Institute of Advanced Studies, University of Sao Paulo, Sao Paulo, Brazil.
³ Renal Division, Department of Clinical Medicine, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
⁴ Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
⁵ Reproductive Toxicology Unit, Department of Pathology, University of Sao Paulo Medical School, São Paulo, Brazil.
⁶ Institute of Advanced Studies, University of Sao Paulo, Sao Paulo, Brazil.
⁷ Department of Clinical Laboratory, University Center of ABC Medical School, Santo Andre, Brazil.

Abstract

The ongoing COVID-19 pandemic represents an extra burden in the majority of public and private health systems worldwide beyond the most pessimistic expectations, driving an urgent rush to develop effective vaccines and effective medical treatments against the SARS-CoV-2 pandemic. The Nucleocapsid structural viral protein is remarkably immunogenic and hugely expressed during infection. High IgG antibodies against Nucleocapsid protein (N protein) levels were detected in the serum of COVID-19 patients, confirming its pivotal antigen role for a T lymphocyte response in a vaccine microenvironment. Currently, adverse events associated with immunizations have raised some degree of concern, irrespective of its huge benefits in dealing with disease severity and decreasing mortality and morbidity. This hitherto study evaluates histological changes in rats' testes, epididymis, prostate, and seminal vesicles and analyzes hormone levels after solely N protein inoculation. Therefore, we exposed a group of Lewis rats to weekly injections of the recombinant N protein for 28 days, while a control group was inoculated with a buffer solution. The N group revealed a more significant number of spermatozoa. Spermatozoa in the seminiferous tubules were counted in twenty 400 × microscopy fields (mean of 9.2 vs. 4.6 in the control group; p < 0,01), but significantly lower testosterone levels (mean of 125.70 ng/dl vs. 309,00 ng/dl in the control group; p < 0,05) were found. No other histological and biochemical changes were displayed. Conclusively, these data suggest testicular hormonal imbalance mediated by the SARS-CoV-2 N protein that could be linked to reported post-COVID-19 syndrome hypogonadism. More relevant research might be performed to confirm this viral antigen's deleterious mechanism in the human testicular microenvironment, particular in Leydig cell function.

Keywords: COVID-19; SARS-CoV-2; hypogonadism; nucleocapsid; testis; testosterone.

Copyright © 2022 Lucio Carrasco, Noda, Barbosa, Vieira Borges da Silva, Gasque Bomfim, Ventura Fernandes, Teixeira, Nunes Duarte Neto, Nascimento Saldiva, Achoa Filho, Rodrigues Guzzo, Durigon, Affonso Fonseca, Corazzini, Fanelli, Noronha and Hallak.