Effects of intrauterine 2,3,7,8-tetrachlorodibenzo-p-dioxin on the development and function of the gonadotrophin releasing hormone neuronal system in the male rat.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental disrupter that continues to be generated from numerous industrial processes. In utero and lactational exposure of rats to levels of TCDD similar to those encountered by human populations have profound and persistent effects on growth, the reproductive axis and spatial learning and memory. TCDD is thought to act through the aryl hydrocarbon receptor, which displays crosstalk with estrogen-mediated genomic activation. An in vitro superfusion system was used to evaluate the effects of TCDD exposure on GnRH-release from hypothalamic explants at three developmental time points in male rats. Pregnant dams were treated with 5 microg/kg TCDD on gestational day 15, and male offspring displayed a marked reduction in GnRH release. However, total mediobasal hypothalamus/preoptic area (MBH/POA) GnRH content was significantly greater in dioxin-exposed animals. These results suggest deficits in release rather than production of GnRH. Confocal microscopy was used to characterize anatomical features of individual GnRH-positive neurons, as well as the organization of the neuronal network governing GnRH release. Differences in cellular structures were apparent in discrete regions of the GnRH neural network, specifically the lateral preoptic area and septal region. We propose that developmental reproductive effects in males treated in utero and lactionally with dioxin, results from a suppressive effect of TCDD on mechanisms governing GnRH release. These effects coincide with changes in growth and development, indicating that TCDD may induce a syndrome of effects by modifying hypothalamic structures regulating growth and reproductive development.