Pregnancy is a complex process requiring tremendous physiological changes in the mother in order to fulfill the needs of the growing fetus, and to give birth, expel the placenta and nurse the newborn. These physiological modifications are accompanied with psychological changes, as well as with variations in habits and behaviors. As a result, this period of life is considered as a sensitive window as impaired functional and physiological changes in the mother can have short- and long-term impacts on her health. In addition, dysregulation of the placenta and of mechanisms governing placentation have been linked to chronic diseases later-on in life for the fetus, in a concept known as the Developmental Origin of Health and Diseases (DOHaD). This concept stipulates that any change in the environment during the pre-conception and perinatal (in utero life and neonatal) period to puberty, can be "imprinted" in the organism, thereby impacting the health and risk of chronic diseases later in life. Pregnancy is a succession of events that is regulated, in large part, by hormones and growth factors. Therefore, small changes in hormonal balance can have important effects on both the mother and the developing fetus. An increasing number of studies demonstrate that exposure to endocrine disrupting compounds (EDCs) affect both the mother and the fetus giving rise to growing concerns surrounding these exposures. This review will give an overview of changes that happen during pregnancy with respect to the mother, the placenta, and the fetus, and of the current literature regarding the effects of EDCs during this specific sensitive window of exposure.

Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression.

Brominated flame retardants (BFR) are molecules added to consumer products to reduce fire hazards. They were banned in North America and Europe because of their persistence and biomagnification. However, BFR are still released in the environment due to continued use of products manufactured before restriction, and from waste and recycling processes of those products. As a result, they remain sources of chronic environmental and human exposure worldwide. BFR are well-characterized endocrine disruptors. They have been associated with a wide range of alterations in endocrine and reproductive systems both in humans and experimental models in vivo and in vitro. Paradoxically, the effects of BFR on mammary glands, whose development and carcinogenesis are mainly under hormonal dependency are poorly known. There is increasing weight of evidence that exposure to endocrine disruptors promotes breast cancer, especially if the exposure occurs during sensitivity windows. For the mammary gland, these windows include the perinatal life, puberty, and pregnancy, as important remodeling of the organ happens during those periods. The peak of exposure to BFRs happened during late 1990s and beginning of 2000s in most countries. Women who were pregnant at that time are reaching menopause while their daughters are 20–30 years old. It is thus important to better understand the effects of BFRs on mammary gland development and breast cancer to determine whether these women are more at risk. Thus, this review aims to propose a comprehensive review of data reporting the effects of exposure to BFR on female endocrine and reproductive systems, with a particular focus on mammary gland development and of a potential increased risk of breast cancer.

Proper mammary gland development and function require precise hormonal regulation and bidirectional cross talk between cells provided by means of paracrine factors as well as intercellular junctions; exposure to environmental endocrine disruptors can disturb these processes. Exposure to one such family of chemicals, the brominated flame retardants (BFRs), is ubiquitous. Here, we tested the hypothesis that BFR exposures disrupt signaling pathways and intercellular junctions that control mammary gland development. Before mating, during pregnancy and throughout lactation, female Sprague-Dawley rats were fed diets containing that BFR mixture based on house dust, delivering nominal exposures of BFR of 0 (control), 0.06, 20, or 60 mg/kg/d. Dams were euthanized and mammary glands collected on postnatal day 21. BFR exposure had no significant effects on mammary gland/body weight ratios or the levels of proteins involved in milk synthesis, epithelial-mesenchymal transition, cell-cell interactions, or hormone signalling. However, BFR exposure (0.06 mg/kg/d) down-regulated phospho-ser675 β-catenin (p-β-cat^Ser675) levels in the absence of any effect on total β-catenin levels. Levels of p-CREB were also down-regulated, suggesting that PKA inhibition plays a role. p-β-cat^Ser675 co-localized with β-catenin at the mammary epithelial cell membrane, and its expression was decreased in animals from the 0.06 and 20 mg/kg/d BFR treatment groups. Although β-Catenin signaling was not affected by BFR exposure, the interaction between p-β-cat^Ser675 and E-cadherin was significantly reduced. Together, our results demonstrate that exposure to an environmentally relevant mixture of BFR during pregnancy and lactation decreases p-β-cat^ser675 at cell adhesion sites, likely in a PKA-dependant manner, altering mammary gland signaling.