Perinatal exposure to bisphenol A impacts in the mammary gland morphology of adult Mongolian gerbils

Leonel, Ellen Cristina Rivas; Campos, Silvana G. P.; Bedolo, Carolina M.; Guerra, Luiz Henrique Alves; Vilamaior, Patrícia Simone Leite; Calmon, Marília Freitas; Rahal, Paula; Amorim, Christiani Andrade; Taboga, Sebastião Roberto

doi:10.1016/j.yexmp.2020.104374

Cited by 9 publications

(7 citation statements)

References 51 publications

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“…These results are different from those described in adult rats, where exposure to BPA upregulated COX-2 (Wu et al, 2020); the authors attribute this increase to the higher levels of serum estrogen. Previous experimentation with Mongolian gerbils showed a decrease in serum levels of estradiol in E2 and BPA perinatally exposed animals (Leonel et al, 2020a(Leonel et al, , 2020b, which may explain the absence of differences in COX-2 expression among groups in the present work.…”

Section: Discussionsupporting

confidence: 47%

Inflammatory repercussions in female steroid responsive glands after perinatal exposure to bisphenol A and 17‐β estradiol

Leonel

Ruiz

Bedolo

et al. 2021

Cell Biology International

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The mammary gland (MG) and female prostate are plastic reproductive organs which are highly responsive to hormones. Thus, endocrine disruptors, such as bisphenol A (BPA) and exogenous estrogens, negatively affect glandular homeostasis. In addition to previously described alterations, changes in inflammatory markers expression also trigger the development of a microenvironment that contributes to tumor progression. The current work aimed to evaluate the inflammatory responses of the MG and prostate gland to BPA (50 µg/kg) and 17‐β estradiol (35 µg/kg) exposure during the perinatal window of susceptibility. The results showed that at 6 months of age there was an increase in the number of phospho‐STAT3 (P‐STAT3) positive cells in the female prostate from animals perinatally exposed to 50 µg/kg BPA daily. In addition, the number of macrophages increased in these animals in comparison with nonexposed animals, as shown by the F4/80 marker. Despite an increase in the incidence of lobuloalveolar and intraductal hyperplasia, the MG did not show any difference in the expression of the four inflammatory markers evaluated: tumor necrosis factor‐α, COX‐2, P‐STAT3, and F4/80. Analysis of both glands from the same animal led to the conclusion that exposure to endocrine disruptors during the perinatal window of susceptibility leads to different inflammatory responses in different reproductive organs. As the prostate is more susceptible to these inflammatory mechanisms, it is reasonable to affirm that possible neoplastic alterations in this organ are related to changes in the inflammatory pattern of the stroma, a characteristic that is not evident in the MG.

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Section: Discussionsupporting

confidence: 47%

Inflammatory repercussions in female steroid responsive glands after perinatal exposure to bisphenol A and 17‐β estradiol

Leonel

Ruiz

Bedolo

et al. 2021

Cell Biology International

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“…The areas of different MG compartments (epithelium, stroma, and adipose tissue) were assessed by analysis of HE sections (three sections per animal from different depths) and evaluated by the adapted M130 multipoint test system (Leonel et al 2020). The incidence and multiplicity of microscopic lesions in the MG of aged female gerbils were also evaluated.…”

Section: Histopathological Analysismentioning

confidence: 99%

“…In the MG, studies analyzing different perinatally exposed experimental models describe the impacts in offspring when mothers are exposed to BPA during pregnancy and lactation (Mileva et al 2014, Mandrup et al 2016, Leonel et al 2020. These exposure periods are susceptible to the development of pathologies in MG, mainly neoplasia (Terry et al 2019), being BPA a triggering agent for the incidence of breast cancer (Soto et al 2013, vom Saal & Vandenberg 2021.…”

Section: Introductionmentioning

confidence: 99%

Mammary carcinoma in aged gerbil mothers after endocrine disruption in pregnancy and lactation

Ruiz

Colleta

Leonel

et al. 2021

Endocrine-Related Cancer

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Compounds that trigger breast cancer onset and establishment are of great interest in biological research. Endocrine disruptors are relevant because they initiate carcinogenesis by changing endocrine pathways. Bisphenol A (BPA), as a ubiquitous xenoestrogen, is largely associated with dysfunctions in the female reproductive system and associated organs. This study proposes an investigation of the mammary gland (MG) in aged Mongolian gerbil (Meriones unguiculatus) mothers after their exposure to BPA in two windows of morphophysiological plasticity: pregnancy and lactation. A low dose (50 μg/kg), and a high dose (5000 μg/kg) were considered and results showed few differences between them. As expected, we observed contrasts among control and BPA-exposed MG. The control groups presented a regressive phase with high apoptotic activity and elastic stroma. However, BPA damaged mammary tissue and provoked multifocal carcinoma development supported by an apparent epithelial-mesenchymal transition (EMT) and reactive stroma establishment. BPA remodeled stromal fibers deposition and enhanced the recruitment of tumor-associated cells, contributing to a tumoral microenvironment. Overexpression of TGF-β1 was induced by BPA in the epithelial compartment of exposed MG and increased expression of metalloproteinases (MMP-2, MMP-3, MMP-9) was present in carcinoma cells. In conclusion, exposure of mothers to BPA during the gestational/lactational window of susceptibility leads to carcinogenic impacts with aging.

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“…The relative frequencies of the acinar epithelium, lumen, and stromal compartment were assessed after Tuschmann's Bleu trichrome using thirty contiguous microscopic fields at ×400 magnification per animal ( n = 5/group). To estimate the relative frequency of collagen fibers, tissue sections were stained by picrosirius‐hematoxylin method and examined under a polarized light microscope, as described by Leonel et al (2020). One tissue section from each animal ( n = 5/group) and 10 random microscopic fields per section was digitalized at ×400 magnification.…”

Section: Methodsmentioning

confidence: 99%

“…The water containing MLT was consumed by animals ad libitum as well as the food. To keep the freshness and constant concentration of MLT, bottles were filled out with volume as close as possible to daily water consumption determined before experiment, protected from light to avoid photodegradation and the liquid content replaced every day, as previously described by Gobbo et al (2015) Leonel et al (2020). One tissue section from each animal (n = 5/group) and 10 random microscopic fields per section was digitalized at ×400 magnification.…”

Section: Introductionmentioning

confidence: 99%

Melatonin ameliorates degenerative alterations caused by age in the rat prostate and mitigates high‐fat diet damages

Tamarindo

Gobbo

Taboga

et al. 2020

Cell Biology International

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Imbalance of sexual steroids milieu and oxidative stress are often observed during aging and correlated to prostate disorders. Likewise, high‐fat intake has been related to prostate damage and tumor development. Melatonin (MLT) is an antioxidant whose secretion decreases in elderly and is also suggested to protect the gland. This study evaluated the impact of a long‐term high‐fat diet during aging on prostate morphology and antioxidant system of rats and tested the effects of MLT supplementation under these conditions. Male rats were assigned into four groups: control, treated with MLT, high‐fat diet and high‐fat diet treated with MLT. The high‐fat diet was provided from the 24th week of age, MLT from the 48th (100 μg/kg/day) and rats were euthanized at the 62nd week. The high‐fat diet increased body weight, retroperitoneal fatness, glycaemia, and circulating estrogen levels. It aggravated the aging effects, leading to epithelial atrophy (∼32% reduction of epithelial height) and collagen fibers increase (83%). MLT alone did not alter biometric and physiological parameters, except for the prostate weight decrease, whereas it alleviated biometric as well as ameliorated acinar atrophy induced by high‐lipid intake. Systemic oxidative stress increased, and prostatic glutathione peroxidase activity decreased fivefold with the high‐fat diet despite the indole. Regardless of the diet, MLT triggered epithelial desquamation, reduced androgen receptor‐positive cells, increased smooth muscle layer thickness (12%), decreased at least 50% corpora amylacea formation, and stimulated prostatic gluthatione‐S‐transferase activity. In conclusion, MLT partially recovered prostate damage induced by aging and the long‐term high‐fat diet and ameliorated degenerative prostate alterations.

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Perinatal exposure to bisphenol A impacts in the mammary gland morphology of adult Mongolian gerbils

Cited by 9 publications

References 51 publications

Inflammatory repercussions in female steroid responsive glands after perinatal exposure to bisphenol A and 17‐β estradiol

Inflammatory repercussions in female steroid responsive glands after perinatal exposure to bisphenol A and 17‐β estradiol

Mammary carcinoma in aged gerbil mothers after endocrine disruption in pregnancy and lactation

Melatonin ameliorates degenerative alterations caused by age in the rat prostate and mitigates high‐fat diet damages

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