Effect of Metformin on Sertoli Cell Fatty Acid Metabolism and Blood–Testis Barrier Formation

Author:

Rindone Gustavo Marcelo1,Dasso Marina Ercilia1,Centola Cecilia Lucia1ORCID,Sobarzo Cristian Marcelo2,Galardo María Noel1ORCID,Meroni Silvina Beatriz1ORCID,Riera María Fernanda1

Affiliation:

1. Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), FEI–División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires C1425EFD, Argentina

2. Instituto de Investigaciones Biomédicas (INBIOMED), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires C1121ABG, Argentina

Abstract

Sertoli cells (SCs) are essential to maintaining germ cell development. Metformin, the main pharmacologic treatment for pediatric type 2 diabetes, is administered to children during SC maturation. The present study aimed to analyze whether metformin affects SC energy metabolism and blood–testis barrier (BTB) integrity. Primary SC cultures were used for the in vitro studies. In vivo effects were studied in Sprague–Dawley rats treated with 200 mg/kg metformin from Pnd14 to Pnd30. Metformin decreased fatty acid oxidation and increased 3-hydroxybutyrate production in vitro. Moreover, it decreased the transepithelial electrical resistance across the monolayer and induced ZO-1 redistribution, suggesting an alteration of cell junctions. In vivo, a mild but significant increase in BTB permeability and ZO-1 expression was observed in the metformin group, without changes in testicular histology and meiosis progression. Additionally, adult rats that received metformin treatment during the juvenile period showed no alteration in BTB permeability or daily sperm production. In conclusion, metformin exposure may affect BTB permeability in juvenile rats, but this seems not to influence spermatogenesis progression. Considering the results obtained in adult animals, it is possible to speculate that metformin treatment during the juvenile period does not affect testicular function in adulthood.

Funder

Consejo Nacional de Investigaciones Científicas y Técnicas

Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación

Publisher

MDPI AG

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