Prenatal exposure to the phthalate DEHP modifies the expression of pituitary estrogen receptors and affects reproductive physiology in the adult

Abstract

Estrogens, acting through Estrogen Receptors (ER) alpha and beta, regulate the pituitary hormonal secretion contributing to the modulation of male sexual function. Estrogenic signaling may be affected by the action of endocrine disruptors such as Di (2-ethylhexyl) phthalate (DEHP), an anthropic product used in plastics manufacture, to which we are highly exposed by inhalation, digestive or dermal route. We proposed to analyze the effect of prenatal exposure to DEHP on the pituitary ER levels and its impact on the reproductive physiology.

Male Wistar rats prenatally treated with DEHP and maintained until sexual maturity were used. At 3.5 months, the body weight was determined and subsequently the animals were sacrificed to quantify the expression of pituitary ER alpha and beta by flow cytometry, determine testicular weight, anogenital distance, sperm concentration and motility. Statistical analysis: ANOVA-Fisher.

Our results showed that prenatal exposure to DEHP decreased the percentage of ERalfa + cells (57.23 ± 0.92% treated vs. 60.19 ± 0.29% controls, P <0.05), together with an increase in ERbeta expression (34.46 ± 3.58% treated vs. 23.13 ± 1.61% controls, P <0.005). The REalfa / beta index was 1.66 ± 0.2 in exposed vs. 2.6 ± 0.09 in controls. A significant decrease in anogenital distance was also observed in prenatally treated animals (1.37 ± 0.06 cm) vs. controls (1.79 ± 0.07 cm)(P <0.05), together with a significant increase in sperm concentration (10.86 x106 ± 1.32 x ml. in treated vs. 6.26 x 106 ± 0.95 x ml. in controls, P <0.05). The percentage of motile sperm did not change significantly. The results also showed a decrease in testicular weight being 2.78 ± 0.03g in exposed vs. 3.49 ± 0.08g in controls (P <0.001), together with a significant increase in body weight of treated animals (356 ± 3.4g) vs. controls (323 ± 1.2g).

These results show that prenatal exposure to the phthalate “DEHP” induces changes in the expression of pituitary ERalfa and beta in adulthood and modifies parameters of the reproductive function.