Given the importance of epigenetic mechanisms in generation of Pb induced neurotoxicity it is necessary now to characterize the role of genetic variants influencing the function of epigenetic regulators such as Dnmts.
The neurotransmitter serotonin which regulates activity of other neurotransmitters such as dopamine and glutamate and is associated with sex specific impulsive choice behavior, has been suggested to play a role in mediating the sex specific behavioral effects of Pb and PS Cory-Slechta et al.
Epigenetics of early-life lead exposure and effects on brain development. In humans and rodents, both the brain and vagina are exquisitely sensitive to circulating hormone concentrations for appropriate differentiation. Brain Research.
Neonatal injection of estrogen causes early vaginal opening in a dose-dependent fashion Del Vecchio, ; Hisano, Imprinting by neonatal sex steroids on the structure and function of the mature mouse prostate.
However, recent findings have challenged this perspective and it has become increasingly clear that environmental cues, integrated with gonadal sex and varying hormone levels during development and later life affect the network of molecular interactions that ultimately result in sex-specific phenotypes McCarthy and Arnold, ; McCarthy et al.
Males and females of each strain also showed differentially enriched sets of genes. Thus, a gene that is maternally silenced would be expressed at a higher level in XX cells but not in XY cells, while a paternally imprinted gene would be more highly expressed in XY than in XX cells.
The effects of perinatal testosterone exposure on the DNA methylome of the mouse brain are late-emerging. Furthermore, aromatase inhibitors have shown promise in the treatment of pelvic pain associated with endometriosis Takayama et al. Although this study only measured blood Pb level at one time point age 11 yearsthe accuracy of male sex in distinguishing between no conviction and conviction exceeded that of blood Pb level, and blood Pb level contributed a minimal increase in accuracy beyond that of male sex Buckley et al.
However, a recent study by Buckley et al. Sexual dimorphism in environmental epigenetic programming.
Psychoneuroendocrinology 62 — Front Genet. Five pieces of chromic gut suture, 1. Toxicology Letters Hu et al. Therefore, testosterone can reach the brain without being taken up by alpha-fetoprotein. Interaction of the delta-aminolevulinic acid dehydratase polymorphism and lead burden on cognitive function: the VA normative aging study.
Effect on hamster vaginal development of a single dose of testosterone or estradiol given neonatally. While "reprogramming" has been proposed as an explanation for some of the effects of endocrine disruptors and estrogens Newbold, ; Palanza et al.
Unfortunately, until very recently, most basic neuroscience and epidemiological studies either excluded females or combined males and females in the analyses, limiting the appreciation of potential sex-dependent outcomes from environmental exposures.