Gestational and lactational exposure to DEHP alters pituitary androgen receptor expression and gonadotroph cell growth

PABLO A. PÉREZ; JONATHAN TOLEDO; AMADO QUINTAR; ANA L. DE PAUL; SILVINA GUTIÉRREZ

Congreso; Sociedades de Biociencia, Sociedad Argentina de Investigación Clínica (SAIC); 2022

SAIC

Di-(2-ethylhexyl)phthalate(DEHP), an endocrine disruptor used in a variety of commercial products,crosses the placental barrier, causing reproductive alterations. The impact onpituitary gland, and in particular, the molecular mechanisms involved arepoorly known. We focused on the DEHP effects on pituitary androgen receptor(AR) expression in male and female rats, and explored their influence ongonadotroph cell growth. For in vivo model, pregnant rats were assigned to 2 groups: DEHP (200µg/kg body weight/day) and control (corn oil), administrated by gavage untilweaning. The offspring were euthanized at postnatal day (PND) 21 (prepubertal)or PND75 (adult) and the pituitary glands were used in this study.For in vitro model, primary pituitary cell cultures were stimulated for72 h with DEHP (1, 10 or 100 nM). The percentage of LH positive cells wasquantified by flow cytometry (FC) and the gonadotroph cell proliferation wasdetermined by double immunostaining for LH and Ki67. ANOVA Fisher (P<0.05).In male rats, DEHP perinatalexposure induced a significant increase of AR expression at PND21 (78.6±1.5%DEHP vs. 54.8±7.8% controls), and at PND75 (50.3±4.3% DEHP vs.37.81±3.34% controls). In contrast, in female rats DEHP increased pituitarycells expressing AR at PND21 (74.6±1.8% DEHP vs. 45±5.2% control), butdecreased it in the adulthood (26.4±4.5% DEHP vs. 44±4.3% controls). Thegonadotroph cell percentage was significantly decreased in the exposed adult female rats (8.9±1.2%) vs.control (13±1.2), showing no differences in adult male rats. Finally, DEHP in vitro significantly decreased LH-Ki67cells in male and female pituitary cultures. These results showed that DEHPexposure during developmental stages induces changes in pituitary AR expressionin a sex dependent manner, differentially manifested in the adulthood,affecting the gonadotroph proliferation. These findings contribute tounderstand the impact of environmental contaminants on the pituitary gland.