Postnatal metformin treatment alters rat Sertoli cell proliferation and daily sperm production

RINDONE, GUSTAVO MARCELO; GORGA, AGOSTINA; PELLIZZARI, ELIANA HERMINIA; DEL CARMEN CAMBEROS, MARÍA; GALARDO, MARÍA NOEL; DA ROS, VANINA GABRIELA; BUFFONE, MARIANO GABRIEL; MERONI, SILVINA BEATRIZ; RIERA, MARÍA FERNANDA

Andrology

Wiley Online Library

Lugar: New Jersey; Año: 2021 vol. 9 p. 965 - 976

Background: The direct correlation between Sertoli cell number and sperm production capacityhighlights the importance of deciphering external factors that modify Sertoli cell proliferation. Agrowing body of evidence in vitro suggests that metformin, the main pharmacological agent fortype 2 diabetes treatment in children, exerts anti-proliferative effects on Sertoli cells.Objective: The aims of this study were to investigate the effect of metformin administrationduring postnatal period on Sertoli cell proliferation and on cell cycle regulators expression and toanalyze the impact of this treatment on the sperm production capacity in adulthood.Materials and methods: Sprague-Dawley rat pups were randomly divided into two groups: MET(receiving daily 200 mg/kg metformin, from Pnd3 to Pnd7 inclusive) and control (receivingvehicle). BrdU incorporation was measured to assess proliferation. Gene expression analyses wereperformed in Sertoli cells isolated from animals of both groups. Daily sperm production and spermparameters were measured in adult male rats (Pnd90) that received neonatal treatment.Results: MET group exhibited a significant decrease in BrdU incorporation in Sertoli cells.Concordantly, MET group showed a reduction in Cyclin D1 and E2 expression and an increase inp21 expression in Sertoli cells. In addition, metformin-treated animals displayed lower values ofdaily sperm production on Pnd90.Discussion and conclusion: These results suggest that metformin treatment may lead to adecrease in Sertoli cell proliferation, a concomitant altered expression of cell cycle regulators andultimately, a reduction in daily sperm production in adult animals