Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems.
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 develop the potential ability to intervene when development is disrupted.
Gore
Andrea C
AC
Division of Pharmacology and Toxicology, Institute for Neuroscience and Institute for Cellular and Molecular Biology, The University of Texas at Austin, 1 University Station A1915, Austin, TX 78712, USA. andrea.gore@mail.utexas.edu
D000818:Animals; D017209:Apoptosis; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D052244:Endocrine Disruptors / Q000494:pharmacology*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009490:Neurosecretory Systems / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects* / Q000502:physiology; D012727:Sex Characteristics; D013256:Steroids / Q000378:metabolism
D052244:Endocrine Disruptors; D009414:Nerve Growth Factors; D018377:Neurotransmitter Agents; D013256:Steroids