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

Abstract

Sertoli cells (SCs) are essential to maintaining germ cell development. Metformin, themain pharmacologic treatment for pediatric type 2 diabetes, is administered to children during SCmaturation. The present study aimed to analyze whether metformin affects SC energy metabolismand 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 Pnd14to Pnd30. Metformin decreased fatty acid oxidation and increased 3-hydroxybutyrate productionin vitro. Moreover, it decreased the transepithelial electrical resistance across the monolayer andinduced ZO-1 redistribution, suggesting an alteration of cell junctions. In vivo, a mild but significantincrease in BTB permeability and ZO-1 expression was observed in the metformin group, withoutchanges in testicular histology and meiosis progression. Additionally, adult rats that receivedmetformin treatment during the juvenile period showed no alteration in BTB permeability or dailysperm production. In conclusion, metformin exposure may affect BTB permeability in juvenile rats,but this seems not to influence spermatogenesis progression. Considering the results obtained inadult animals, it is possible to speculate that metformin treatment during the juvenile period doesnot affect testicular function in adulthood.