Mediating Roles of PPARs in the Effects of Environmental Chemicals on Sex Steroids

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that are widely involved in various physiological functions. They are widely expressed through the reproductive system. Their roles in the metabolism and function of sex steroids and thus the etiology of reproductive disorders receive great concern. Various kinds of exogenous chemicals, especially environmental pollutants, exert their adverse impact on the reproductive system through disturbing the PPAR signaling pathway. Chemicals could bind to PPARs and modulate the transcription of downstream genes containing PPRE (peroxisome proliferator response element). This will lead to altered expression of genes related to metabolism of sex steroids and thus the abnormal physiological function of sex steroids. In this review, various kinds of environmental ligands are summarized and discussed. Their interactions with three types of PPARs are classified by various data from transcript profiles, PPRE reporter in cell line, in silico docking, and gene silencing. The review will contribute to the understanding of the roles of PPARs in the reproductive toxicology of environmental chemicals.

Mitochondrial Involvement in the Adaptive Response to Chronic Exposure to Environmental Pollutants and High-Fat Feeding in a Rat Liver and Testis

“…In fact, PPARs not only regulate cellular proliferation, but also play an anti-inflammatory role and maintain lipid homeostasis in Kupffer cells, hepatocytes, and stellate cells [105]. Moreover, the induction of PPARγ gene expression in the presence of DDT has been seen in human mesenchymal stem cells, [106] suggesting that PPARs, as well as other nuclear receptors, are involved in the cellular response to toxicant.…”

PPAR-Mediated Toxicology and Applied Pharmacology

“…Three isoforms of PPARs were found in the reproductive system including the hypothalamus, pituitary, testis, ovary, uterus, adrenal, and mammary glands. Numerous studies showed that PPARs play a role in the normal reproductive and developmental functions, and abnormal regulation of PPARs by exposure to endogenous or exogenous compounds might lead to physiological dysfunction in reproductive system [84][85][86]. Thus, the research on reproductive and developmental disorders focuses on PPARs and their modulators.…”

Xenobiotic Receptors and Their Mates in Atopic Dermatitis

“…Interestingly, PPARα can be activated by xenobiotics, such as phthalates, tributyltin, PCBs, bisphenols, DDT, perfluorooctanoic acid and perfluorooctanesulfonic acid to induce peroxisome proliferation and exert deleterious effects on cells [47,252,253,254,255,256]. Moreover, several genes involved in xenobiotic metabolism are regulated by PPARα [257,258].…”

“…Therefore, PPARα might be involved in the toxic effects caused by environmental pollutants. Notably, several studies have demonstrated the impact of such molecules on the metabolism and function of sex steroids through PPAR signaling [254]. This might be relevant in skin diseases, including AD [260].…”