Perinatal exposure to the phthalate "DEHP" alters the expression of estrogen receptors on somatotroph cells, increasing their proliferation

Abstract

Abstract: 

Phthalates are chemicals widely used to make soft and flexible plastics. Di-2-ethylhexyl phthalate (DEHP) is the most commonly used, with high human exposure occurring from fetal development, acting as an endocrine disruptor by interfering with hormonal signaling. The objective of this study was to analyze the effect of perinatal exposure to DEHP on pituitary Estrogen receptor (ER)α and β expression and its impact on somatotroph cells. 

For this, 10 pregnant Wistar rats were exposed by gavage to DEHP (200 µg / kg) or corn oil from day 0 of gestation, during pregnancy and lactation. For In vivo experiments, glands from 30 75-day-old male pups were used. For in vitro experiments, 3 pituitary cultures from 10 male rats were stimulated with 1, 10 or 100nM DEHP for 72 h. The percentages of somatotroph cells expressing ERα and β were quantified in pituitary cryosections by double immunostaining using confocal microscopy. Cell proliferation was quantified by double immunostaining (ki67+ GH+). The somatotroph cell population was quantified in vivo and in vitro by flow cytometry and immunocytochemistry, respectively. Statistical analysis: ANOVA Tukey (P <0.05).

Our results showed that perinatal exposure to DEHP significantly increased the percentage of somatotrophs that expressed ERα (GH+ ERα+) with values ​​of 46.08 ± 1.36% vs. Controls (43.23 ± 1.13%). Furthermore, the percentage of somatotrophs expressing ERβ (GH+ ERβ+) also increased significantly after exposure to DEHP, with values ​​of 29.38 ± 0.65% in DEHP and 25.83 ± 0.81% in controls. DEHP induced a significant increase in the somatotroph population (60.8 ± 1.19%) compared to the control (47.33 ± 4.21%). In vitro, DEHP significantly increased the proliferation of somatotrophs (Ki67+ GH+), and the total somatotroph cell population, with values ​​of 16.08 ± 0.9% with DEHP 1nM, 20.81 ± 0.41% DEHP 10nM and 18.6 ± 0.39% DEHP 100nM, vs. control (11.98 ± 0.44%).

These results showed that DEHP increased the expression of ERα and β in the somatotroph cell population of male rats in vivo and in vitro, increasing their proliferation, possibly as a consequence of the imbalance in the expression of ERs.