Environmental chemical TCPOBOP disrupts milk lipid homeostasis during pregnancy and lactation

Abstract

Humans are exposed to different kinds of environmental contaminants or drugs throughout their lifetimes. The widespread presence of these compounds has raised concerns about the consequent adverse effects on lactating women. The constitutive androstane receptor (CAR, Nr1i3) is known as a xenobiotic sensor for environmental pollution or drugs. In this study, the model environmental chemical 1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene, TCPOBOP (TC), which is a highly specific agonist of CAR, was used to investigate the effects of exogenous exposure on lactation function and offspring health in mice. The results revealed that TC exposure decreased the proliferation of mammary epithelial cells during pregnancy. This deficiency further compromised lobular-alveolar structures, resulting in alveolar cell apoptosis, as well as premature stoppage of the lactation cycle and aberrant lactation. Furthermore, TC exposure significantly altered the size and number of milk lipid droplets, suggesting that TC exposure inhibits milk lipid synthesis. Additionally, TC exposure interfered with the milk lipid metabolism network, resulting in the inability of TC-exposed mice to efficiently secrete nutrients and feed their offspring. These findings demonstrated that restricted synthesis and secretion of milk lipids would indirectly block mammary gland form and function, which explained the possible reasons for lactation failure and retarded offspring growth.

Keywords: Alveolar apoptosis; Cell proliferation; Lactation failure; Mammary gland; Milk lipid synthesis; TCPOBOP.