Male mammary gland development and methylation status of estrogen receptor alpha in Wistar rats are modified by the developmental exposure to a glyphosate-based herbicide. (5th February 2019)

• Record Type: Journal Article
• Authors: Gomez, Ayelen L.; Altamirano, Gabriela A.; Leturia, Jorgelina; Bosquiazzo, Verónica L.; Muñoz-de-Toro, Mónica; Kass, Laura
• Is Part Of: Molecular and cellular endocrinology. Volume 481(2019)
• Page Start: 14
• Page End: 25
• Publication Date: 2019-02-05
• Subjects: Glyphosate-based herbicide -- Male -- Rat mammary gland -- Estrogen receptor alpha -- DNA methylation; AMPA aminomethylphosphonic acid -- AR androgen receptor -- ESR1 estrogen receptor alpha -- E2 estradiol -- F0 dams directly exposed to GBH -- GBH glyphosate-based herbicide -- GD gestational day -- LD lactation day -- LN lymph node -- LOD limit of detection -- LOQ limit of quantification -- PND postnatal day -- PRL prolactin -- TEBs terminal end buds -- T testosterone -- WM whole-mount; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2018.11.005
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Postnatal treatment with glyphosate-based herbicides (GBHs) induces endocrine-disrupting effects on the male rat mammary gland. In this study, the effects of developmental exposure to GBH on mammary gland growth and development, and the possible molecular mechanisms involved, were evaluated in pre- and post-pubertal male rats. To this end, pregnant rats were orally exposed through the food to 0, 3.5 or 350 mg GBH/kg bw/day from gestational day 9 until weaning. Mammary gland development and estradiol (E2) and testosterone (T) serum levels of male offspring were evaluated on postnatal day (PND)21 and PND60. Besides, prolactin (PRL) serum levels, proliferation index, androgen (AR) and estrogen receptor alpha (ESR1) expression, ESR1 alternative transcript mRNA levels, and DNA methylation status of ESR1 promoters were assessed on PND60. No differences between groups were observed in mammary gland development at PND21 or in E2 and T levels on both PNDs studied. On PND60, GBH3.5-exposed animals presented similar mammary gland histology but higher AR protein expression than controls, whereas GBH350-exposed males presented a less developed mammary gland, accompanied by a lower proliferation index, similar AR levels, and slightly increased PRL serum levels than controls. In both exposed groups, ESR1 expression was lower than in control rats, being lower in GBH350-exposed rats. GBH also altered the abundance of ESR1 transcript variants by hypermethylation of ESR1 promoters. GHB3.5 decreased only ESR1-OS expression, whereas GBH350 affected ESR1-O, OT and E1 expression. Our results show that developmental exposure to GBH induces epigenetic changes in ESR1, which could be responsible for the altered male mammary gland development observed in GBH350-exposed animals. Highlights: Developmental exposure to GBH modifies mammary gland development in male rats. GBH decreases ESR1 protein and mRNA expression in the male mammary gland. GBH induces epigenetic changes in ESR1 promoters in post-pubertal males.