Sexually Dimorphic Effects of Early-Life Exposures to Endocrine Disruptors: Sex-Specific Epigenetic Reprogramming as a Potential Mechanism

Abstract

Purpose of review The genetic material of every organism exists within the context of regulatory networks that govern gene expression—collectively called the epigenome. Animal models and human birth cohort studies have revealed key developmental periods that are important for epigenetic programming and vulnerable to environmental insults. Thus, epigenetics represent a potential mechanism through which sexually dimorphic effects of early-life exposures such as endocrine disrupting chemicals (EDCs) manifest. Recent findings Several animal studies, and to a lesser extent human studies, have evaluated life-course sexually dimorphic health effects following developmental toxicant exposures; many fewer studies, however, have evaluated epigenetics as a mechanism mediating developmental exposures and later outcomes. Summary To evaluate epigenetic reprogramming as a mechanistic link of sexually dimorphic early-life EDCs exposures, the following criteria should be met: 1) well characterized exposure paradigm that includes relevant windows for developmental epigenetic reprogramming; 2) evaluation of sex-specific exposure-related epigenetic change; and 3) observation of a sexually dimorphic phenotype in either childhood, adolescence, or adulthood.

Maternal levels of endocrine disrupting chemicals in the first trimester of pregnancy are associated with infant cord blood DNA methylation

“…Observations from human cohort studies suggest BPA can influence epigenetic programming of fetal liver enzymes [23] and imprinted genes [24]. Interestingly, perinatal BPA-induced epigenetic effects are commonly sex specific [25] and linked to DNA methylation changes at a number of loci including genes involved in liver beta oxidation [26], energy homeostasis [27], and growth and metabolism [24,28]. Maternal exposure to phthalates averaged across pregnancy has been found to be inversely associated with methylation profiles of retrotransposons Alu and LINE-1 in a population of Mexican-American children [29].…”

Potential Health Risk of Endocrine Disruptors in Construction Sector and Plastics Industry: A New Paradigm in Occupational Health

“…Endocrine disruptors (EDs) belong to a wide range of different substances, which interfere with mammalian hormone biosynthesis, transport, metabolism and receptors, affecting homeostasis, development, and aging, reduce fertility in both sexes and are linked with the etiology of both malignant and non-malignant diseases [ 1 , 2 , 3 , 4 , 5 , 6 ]. The biological effects of EDs are complex and do not only depend on dose, but also on the timing of exposure and the sex of the exposed subject [ 7 ]. The complex interplay between timing and dose can lead to a broad array of different effects [ 8 ].…”

Prenatal Exposure to Acetaminophen and Overweight in Childhood

“…The positive association observed for girls at 11 years might indicate a sex‐hormone‐specific mechanism of the exposures , but it could also be explained by the timing of pubertal growth and outcome measures in our study. Some girls might have started entering puberty at age 11, while for most boys, this is still considered a prepubertal period .…”