Postnatal exposure to metformin: effects on rat Sertoli cell proliferation

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

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

Sertoli cell (SC) proliferation, a factor defining SC population size, occurs during a restricted period of time. In rats, fetal and postnatal periods up to 15 days of age constitute the time period for SC mitosis. Metformin (MET), a first line anti-hyperglycemic agent, has started to be used in pediatric population at ages when SCs are still proliferating. In addition to its strong anti-diabetic properties, numerous studies have demonstrated that MET has anti-proliferative activity. Additionally, we have previously demonstrated in SC cultures obtained from 8-day old rats that MET decreases basal and FSH-stimulated SC proliferation. The aim of this study was to analyze the in vivo relevance of MET treatment on SC proliferation. At postnatal day 3 (Pnd3), rat pups were randomly assigned to the following groups: MET (receiving daily 200 mg/kg MET i.p., day 3-7) and control group (receiving daily sterile saline solution i.p.). At Pnd8, a set of animals were injected with BrdU (50 mg/kg i.p.) before sacrifice to evaluate cell proliferation. In another set of animals, testes were utilized to perform SC isolation for gene expression analysis. Our results showed that MET group exhibited a significant decrease in BrdU incorporation in SC compared to controls (n=6 p