Reproduction Abstracts

Alterations in the fetal environment can alter lifetime risk of certain diseases. This also applies to reproductive function/disorders in adulthood, and we have shown that fetal androgens play a pivotal time-specific role in this regard in males.

One interpretation of the ‘fetal reprogramming’ changes that can result in adult metabolic dysfunction is that it represents an adaptive change that better fits the fetus for life after birth. As our evolution has been geared primarily for reproductive fitness, and as the germ cells undergo extensive epigenetic remodeling in fetal life in both sexes, it raises the question of whether ‘fetal reprogramming of the germ cells’ might also occur in response to an altered fetal environment. In this case, however, any consequences of such reprogramming are not seen in the exposed fetus when it matures but in the offspring that may arise from the ‘altered’ germ cells. The evidence for such inter-generational effects is growing steadily, but is largely unexplored.

In searching for fetal causes of adult male reproductive disorders, we discovered that paracetamol exposure at therapeutic levels inhibits testosterone production by the fetal human testis. Unexpectedly, we discovered that paracetamol and other analgesics also target the fetal germ cells in both sexes (rats), altering their numbers and expression of the germ cell ‘epigenetic machinery’. Consequently, offspring derived from these ‘affected’ germ cells show an altered reproductive phenotype. This talk will use this and other examples (e.g. dietary manipulation) to illustrate how ‘fetal reprogramming’ may extend also to the germ cells/reproduction.