There is now considerable evidence that male reproductive function is declining in human and wildlife populations.
This is coincident with the increasing use and prevalence of man-made chemicals in the environment over the last fifty years.
Certain chemicals have subsequently been shown to disturb the developing fetal endocrine system of laboratory animals in utero.
In these experiments, treatment caused similar male reproductive problems in offspring as those already observed in wildlife and human populations.
In addition, both the human DES data and rodent studies have shown that there are specific windows of gestation when the developing fetal gonad is highly sensitive to small endocrine changes.
Animal in vivo and human in vitro studies have identified EDC sensitive genes.
Consequently, hypotheses are being generated concerning mechanism of action e.g. disturbed testicular apoptosis and altered hepatic biotransformation of steroids.
While animal studies provide us with valuable insights into the range of effects that can be attributed to in utero EDC exposure, varying maternal doses employed by different research groups make relation of the results to human observations difficult.
The EDC concentration representative of fetal exposure levels is uncertain. Confounding factors include: (a) the vast number of chemicals termed EDCs, (b) the ability of chemicals to bioaccumulate in body lipid, (c) the metabolism of body lipid during pregnancy releasing the mothers lifetime EDC legacy into circulation and (d) the poorly understood kinetics of EDC transfer across the placenta. Thus, the level of fetal exposure can only be crudely estimated at present.
This highlights the need for large animal models of EDC in utero exposure where the partitioning of EDCs between the mother and fetus and transfer across the placenta can be studied in detail. Despite considerable effort the mechanisms by which these endocrine disrupting chemicals exert their effects are still largely unknown.
Further studies of the mechanism of action, and consequences, of EDCs in fetal development must be done in order to elucidate how EDCs exert their effects.
This can only be achieved using a combined approach whereby animal models are used in combination with in vitro human studies.
In conclusion however, there are now sufficient animal model data to prove that EDCs can adversely affect reproductive development and function in the male.
Our further understanding of the mechanisms involved may allow intervention strategies whereby we can at least prevent a further decline in male as well as female reproductive health.
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