A new study by researchers in the UK examining the activity of hormones in male foetuses suggests that the health of male reproductive organs could be established before birth. The findings may help to explain the development of common genital disorders that increase the risk of testicular cancer, and the risk of having a low sperm count and other reproductive problems.
The study was the work of Dr Michelle Welsh of the Human Reproductive Sciences Unit at the Medical Research Council (MRC) in Edinburgh, and colleagues, and is published online in the Journal of Clinical Investigation.
Welsh discovered, while working towards her doctorate, that the development of a healthy male reproductive system depends on hormones like testorone doing specific things during the “male programming window”, which Welsh and colleagues estimates to occur during weeks 8 to 14 in human pregnancies.
“Problems like the testes not descending correctly into the scrotum (cryptorchidism) or the urinary tract opening in the wrong place on the penis (hypospadias) are remarkably common in boys at birth,” said Welsh.
Cryptorchidism is estimated to occur in 2.4 to 9 per cent of boys before they are one year old, while hypospadias occurs in 0.4 to 1 per cent of boys at birth, according to background information from the MRC.
Welsh and colleagues exposed rat foetuses to either androgen (male hormones) or anti-androgen during the male programming window.
The results showed that:
- Androgen must act during the male programming window for the male reproductive organs to develop healthily.
- The level of androgen activity during the male programming window was linked to the distance between the base of the penis and the anus (the anogenital distance).
The anogenital distance was therefore a lifelong measure of the level of male hormone activity during the critical period of male reproductive development in the foetus.
This could be used to anticipate future reproductive problems in baby boys, said Welsh:
“Because the distance between the genitals and the anus indicates the degree of androgen activity during this time, measuring this distance in baby boys could offer an early warning system to predict future reproductive problems.”
The anogenital distance could also be used in future studies to better understand what happens in foetal life in a way that is difficult to study in humans, said Welsh. She gave an example:
“Say a clinician were to examine a 30-year-old man with testicular cancer,” said Welsh, “previously there would have been no way of knowing what hormones he was exposed to in the womb.”
But, explained Welsh, even 30 years later this measure “could offer an indication of hormone exposure. For example, the shorter the distance, the less confident we can be that hormones have acted correctly and at the right time,” she added.
“Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism.”
Michelle Welsh, Philippa T.K. Saunders, Mark Fisken, Hayley M. Scott, Gary R. Hutchison, Lee B. Smith and Richard M. Sharpe.
J. Clin. Invest. Published online, March 13, 2008.
DOI:10.1172/JCI34241.
Sources: Press release from the Medical Research Council.
Written by: Catharine Paddock, PhD