Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

Abstract

The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted.

Epigenetics and its implications for behavioral neuroendocrinology

“…The best examples of Context-Dependent epigenetic modifications are those that either have an effect early in life, such as exposure to endocrine disrupting compounds in utero or smoking during childhood and adolescence (known collectively as the fetal basis of adult disease; see article [39]). In the first instance the onset of disease manifests later or the deleterious effects decline with time.…”

“…This organizational principal should also apply to epigenetic modifications whether within the individual's own life history (Context-Dependent) or inherited from previous generations (Germline-Dependent) (see articles [16,39]). What follows are two case studies, the first demonstrating how the genetic and litter environment influence later adult behavior and the neural circuitry underlying these behaviors.…”

Insecticide distribution model in human tissues viewing worker's health monitoring programs

“…These findings are also relevant, as children of agricultural workers are considered to have a higher risk of exposure to pesticides compared to the general population because of the close proximity of their homes to the fields where pesticides are applied and from take-home exposure (Quandt et al, 2004). Another aspect of concern is the increasing damage in reproductive system as the decrease in male fertility observed during the last decades, probably due to estrogenic and anti-androgenic effects during intra-uterine exposure to organochlorines (Nunes and Tajara, 1998;Gore, 2008). Octanol-water partition coefficient, water solubility and tissue lipid contents are important factors in an insecticide distribution determination in human tissues.…”

Effect of <i>in utero</i> exposure to endocrine disruptors on fetal steroidogenesis governed by the pituitary-gonad axis: a study in rats using different ways of administration

“…It has long been suspected that a number of endocrine disruptors hinder the reproduction and development of humans and wild life, disturbing the transfer of correct phenotypes to the next generations (Gore, 2008;Schug et al, 2011;Frye et al, 2012;Fudvoye et al, 2014). However, the detailed mechanism as well as the exact magnitude of their adverse effects on reproduction is not yet fully understood.…”