Impact of gestational low protein diet and postnatal bisphenol A exposure on chemically induced mammary carcinogenesis in female offspring rats

Abstract

This study evaluated the effect of gestational low protein diet (LPD) and/or postnatal bisphenol A (BPA) exposure on mammary gland development and carcinogenesis in female offspring. Pregnant Sprague‐Dawley rats were fed a normal protein diet (NPD, 17% protein) or LPD (6% protein). At weaning, female offspring were distributed in four groups (NPD, LPD, NPD + BPA, and LPD + BPA) and received vehicle or BPA in drinking water (0.1%), during postnatal day (PND) 21 to 51. On PND 51, some female offspring were euthanized or received a single dose of 7,12‐dimethylbenzoanthracene (DMBA, 30 mg/kg, i.g.) and were euthanized on PND 250. On PND 51, neither gestational LPD nor postnatal BPA exposure, individually or in combination, significantly altered the development of mammary gland tree, mean number of terminal structures or estrogen receptor beta (ER‐β), proliferating cell nuclear antigen (PCNA) or caspase‐3 protein expression in the mammary tissue. A significant reduction in mammary epithelial area (%) was observed in both LPD groups and a significant increase in ER‐α protein expression was detected only in LPD group. In LPD + BPA group was observed a significant increase in both fat pad area (%) and in mean number of mammary epithelial cells positive for progesterone receptor (PR). On PND 250, the groups that received BPA presented lower latency and higher tumor incidence and tumor multiplicity and LPD + BPA group more aggressive tumors. These findings suggest that postnatal BPA exposure associated with gestational LPD is able to induce morphological changes in the mammary gland and increase susceptibility to mammary carcinogenesis.

Maternal Low-Protein Diet Deregulates DNA Repair and DNA Replication Pathways in Female Offspring Mammary Gland Leading to Increased Chemically Induced Rat Carcinogenesis in Adulthood

“…Body weight at birth (PND 1) and weaning (PND 21) and body weight evolution of groups are indicated in Table 1 . In the present study, we observed that maternal low protein restriction influenced offspring body weight, which is in line with other experimental and human studies ( Fernandez-Twinn et al, 2007 ; Herring et al, 2018 ; Bautista et al, 2019 ; Varuzza et al, 2019 ; Yang et al, 2020 ). During the experimental period (PND 1 to PND 250), the body weight of female offspring whose dams were fed an LPD was significantly lower ( p < 0.001) than female offspring whose dams were fed with NPD.…”

“…Besides, the chemically induced carcinogenesis model is an important tool to study the multistep process of mammary carcinogenesis (Russo and Russo, 1996;Russo, 2015). Using a maternal LPD model, our research group and others reported important changes in several organs, such as liver, mammary gland, pancreas, prostate, and adipose tissue (Plank et al, 2006;Fernandez-Twinn et al, 2007;Beinder et al, 2014;Santos et al, 2019;Varuzza et al, 2019;Alejandro et al, 2020;de Oliveira Lira et al, 2020). Fernandez-Twinn et al (2007) were the first to demonstrate the adverse effects of gestational and lactational LPD on N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis model in female offspring from Wistar rats, using a total of three 50 mg/kg body weight (b.w.)…”

Effects of mammalian target of rapamycin and aryl hydrocarbon receptor‐mediating autophagy signaling on the balance of Th17/Treg cells during perinatal bisphenol A exposure in female offspring mice

“…Environmental concentration of BPA exposure can increase the risk of cancer 23 . Additionally, epidemiological and experimental studies suggest that BPA exposure early in life may have permanent and adverse effects on the health of developing organisms 24 . Broadly, this indicated that the effect of the low level of BPA exposure on infants should be pained more attention.…”

“…23 Additionally, epidemiological and experimental studies suggest that BPA exposure early in life may have permanent and adverse effects on the health of developing organisms. 24 Broadly, this indicated that the effect of the low level of BPA exposure on infants should be pained more attention. In this study, we conducted a manner of perinatal BPA exposure via drinking water.…”

miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach

“…Several studies pointed to an increased incidence of cardiometabolic disease, diabetes, and schizophrenia in individuals born during this period [ 7 , 8 , 9 ]. In addition, experimental and epidemiological studies also support the DOHAD concept and point out that exposure to adverse environmental conditions during early life impacts not only the incidence of non-communicable chronic diseases but also triggers the carcinogenesis process, including breast and prostate cancer, in descendants [ 10 , 11 , 12 , 13 , 14 , 15 ]. In this regard, Elias et al (2004) [ 16 ] found that girls (2 to 9 years old) exposed to famine during the Dutch hunger winter had a higher incidence of breast cancer.…”