The interface of sexual differentiation, endocrine disruptors, maternal programming, and energy balance
2014 Study Highlights
- Endocrine disruptors are ubiquitous in the environment and affect energy balancing systems.
- Energy balancing phenotypes are sexually dimorphic.
- Endocrine disruptors interfere with sexual differentiation.
- Maternal programming and other epigenetic effects disrupt similar processes.
Our stolen figures: The interface of sexual differentiation, endocrine disruptors, maternal programming, and energy balance, science direct, Hormones and behavior, doi.org/10.1016/j.yhbeh.2014.03.011, 28 March 2014.
A Venn diagram of the interface of sexual differentiation, endocrine disruptor action, and maternal programming of energy balancing traits credit NCBI PMC3339448 Jay Alexander.
This article is part of a Special Issue “Energy Balance”. The prevalence of adult obesity has risen markedly in the last quarter of the 20th century and has not been reversed in this century. Less well known is the fact that obesity prevalence has risen in domestic, laboratory, and feral animals, suggesting that all of these species have been exposed to obesogenic factors present in the environment. This review emphasizes interactions among three biological processes known to influence energy balance: Sexual differentiation, endocrine disruption, and maternal programming. Sexual dimorphisms include differences between males and females in body weight, adiposity, adipose tissue distribution, ingestive behavior, and the underlying neural circuits. These sexual dimorphisms are controlled by sex chromosomes, hormones that masculinize or feminize adult body weight during perinatal development, and hormones that act during later periods of development, such as puberty. Endocrine disruptors are natural and synthetic molecules that attenuate or block normal hormonal action during these same developmental periods. A growing body of research documents effects of endocrine disruptors on the differentiation of adipocytes and the central nervous system circuits that control food intake, energy expenditure, and adipose tissue storage. In parallel, interest has grown in epigenetic influences, including maternal programming, the process by which the mother’s experience has permanent effects on energy-balancing traits in the offspring. This review highlights the points at which maternal programming, sexual differentiation, and endocrine disruption might dovetail to influence global changes in energy balancing traits.
Endocrine disruptors, sexual differentiation, brain, and behavior
A few studies have emerged demonstrating that endocrine-disrupting compounds can masculinize or feminize energy balancing traits. For example, perinatal exposure of rats to BPA masculinizes some aspects of the energy balancing neural circuits via ER, but has other effects that are not masculinizing and might be independent of ER. This suggests that the sexual dimorphisms in rat energy balance are partially explained by the aromatization hypothesis. This effect is mimicked by perinatal exposure to BPA. Pregnant and lactating mice fed diets that contained either a low or a high dose of BPA, a vehicle, or the estrogenic endocrine disruptor, DES, were allowed to grow to adults and their energy balancing traits were examined in detail. Offspring were weaned initially onto a normal laboratory chow diet, then as adults they were exposed to either a normal or an energetically-dense diet. Females exposed to the high dose of BPA, but not those exposed to DES show a masculinized propensity for diet-induced obesity, with increased levels of body weight, WAT gain, and increased levels of food intake compared to untreated females fed the same high-energy diet. Furthermore, BPA-treated but not DES-treated females on a high-energy diet show masculinized plasma leptin concentrations, ARH POMC projections, and ARH ER expression i.e., significantly increased plasma leptin concentrations, reduced POMC mRNA expression in the ARH, and increased ER expression in the ARH. By contrast, males exposed to the high dose of BPA, but not those exposed to DES show impaired glucose tolerance on both high-energy and low-energy diets. They also show reduced ARH POMC projections to the PVH. When exposed to energetically-dense diets, BPA treated males show greater NPY/AgRP expression in the ARH. In sum, exposure to BPA but not to DES hypermasculinizes males masculinizes females and these effects appear to be independent of ER . In addition, BPA has other effects that cannot be described as masculinizing, but these experiments did not manipulate the response to adult hormones (testosterone vs. estradiol plus progesterone). Furthermore, there is still a question as to whether changes in the ARH are secondary to or independent of changes in lipid accumulation or other peripheral factors.