Neonatal exposure to ethinylestradiol increases ventral prostate growth and promotes epithelial hyperplasia and inflammation in adult male gerbils

Abstract

The aim of this study was to analyse morphologically the ventral prostate of adult Mongolian gerbils exposed to ethinylestradiol (EE) during the first week of postnatal development. Lactating females received daily, by gavage, doses of 10 μg/kg of EE diluted in 100 μl of mineral oil from the 1st to 10th postnatal day of the pups (EE group). In the control group (C), the lactating females received only the vehicle. Upon completing 120 days of age, the male offspring were euthanized and the prostates collected for analyses. We employed morphological, stereological-morphometrical, immunohistochemical and ultrastructural methods. The results showed that the postnatal exposure to EE doubled the prostatic complex weight, increasing the epithelial and stromal compartments, in addition to the secretory activity of the ventral lobe of the prostate. All glands exposed to EE showed strong stromal remodelling, and some foci of epithelial hyperplasia and inflammatory infiltrate in both luminal and epithelial or stromal compartments. Cells positive for anti-AR and anti-PCNA reactions increased into the epithelial and stromal tissues. ERα-positive cells, which are normally found in the stromal compartment of intact prostates, were frequently observed in the prostatic epithelium of treated animals. This study demonstrated that the exposure to EE during postnatal development causes histophysiological alterations in this gland, predisposing to the development of prostatic lesions during life. These results are important for public health, considering that women worldwide have commonly used EE. Moreover, the bioaccumulation of this chemical has increased in different ecosystems.

Oral exposure to low-dose bisphenol A induces hyperplasia of dorsolateral prostate and upregulates EGFR expression in adult Sprague-Dawley rats

“…ethinylestradiol on the prostate of gerbils (Falleiros-Junior et al, 2016), indicating an important role of AR in the synergistic effect of estrogen and androgen on the prostate. Low-dose BPA might bind to AREs and activate the existing AR to improve its response ability to low-level androgen (Wu et al, 2013).…”

“…Studies indicated that BPA could induce ERα upregulation, which related to prostate cell proliferation (Huang et al, 2017) and prostate hyperplasia (Campos et al, 2015). AR in prostate was usually increased by low-dose E 2 and DES treatments (Falleiros-Junior et al, 2016; Nonneman et al, 1992) and decreased by a high concentration of estrogen (Prins and Birch, 1995). Hence, the range of E 2 /T ratio was critical for the expression of AR.…”

Ethinylestradiol and its effects on the macrophages in the prostate of adult and senile gerbils

“…As in the adult male prostate, we also observed an increase in epithelial compartment volume, epithelial height, and thickness in smooth muscular layer. Neonatal exposure to estrogen is associated, in adult life, with the onset of prostatic disorders, such as inflammation and premalignant lesions (Coffey and Buchanan 2001; Prins et al, 2001; Perez et al, 2011; Falleiros‐Júnior et al, 2016).…”

“…The stromal remodeling may have been caused by an increased recruitment of macrophages, especially in the stroma, where this cell type can secrete different chemical and enzymatic mediators, actively participating in tissue remodeling (Silva et al, 2018), such as extracellular matrix metalloproteinases of types 2 and 9, as observed in prostate cancer in mice (Fang et al, 2013), in altered prostate tissue of male and female gerbils (Rochel‐Maia et al, 2011) and tissue remodeling in models with hydroxyapatite grafting, or in periodontal lesions (Carneiro et al, 2009; Zambuzzi et al, 2009). According to Falleiros‐Junior et al (2016), exposure to EE during the neonatal period promotes an increase in morphological alterations, such as foci of epithelial hyperplasia associated with inflammations in the stromal and luminal compartments of the ventral prostate of adult gerbils.…”

Cell junctions in the prostate: an overview about the effects of Endocrine Disrupting Chemicals (EDCS) in different experimental models

“…Estrogenic activity can also be shown with the use of synthetic estrogens, such as ethinylestradiol (EE), used as a contraceptive and in hormonal therapies, widely dispersed in the environment due to its low degradation [54]. Falleiros-Júnior et al [55] and Perez et al [56] showed that both neonatal (10 μg/kg) and pubertal exposure (15 μg/ kg), respectively, promote repercussions on the adult prostate. Both studies reported the presence of hyperplastic areas associated with stromal and luminal inflammatory foci.…”