Mar 20 2008
A discovery by Medical Research Council scientists looking at the development of male foetuses could help explain the origin of common genital disorders that can cause reproductive problems or increase risk of low sperm counts and possibly testicular cancer later in life.
Development of healthy male reproductive organs relies on hormones acting at an earlier stage in foetal life than previously thought. If a group of hormones, called androgens which include testosterone, don't act during what's been termed the “male programming window” early in pregnancy then the male reproductive system will not form correctly.
The critical influence of male sex hormones during the male programming window was uncovered by Dr Michelle Welsh of the Medical Research Council Human Reproductive Sciences Unit in Edinburgh while working towards her doctorate. The results are published online in the Journal of Clinical Investigation.
Dr Welsh said: ‘‘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.''‘‘Using rats as an animal model of human development, we have identified that these disorders result from reduced male hormone action at an early stage in development that we call the male programming window. This correlates to weeks 8-12 during human pregnancy.''
In the study, rat foetuses were exposed to either an androgen or an anti-androgen during the male programming window. The results showed that for male reproductive organs to develop healthily androgen must act during this window. They also found that the level of androgen activity only during the male programming window determines the distance between the base of the penis and the anus (anogenital distance) making this measurement a life-long gauge of androgen exposure in the womb during this critical time window.
The research highlighted this simple way to gain an insight into early hormone activity. Because the anogential distance indicates the level of hormone activity there has been in the critical time window, future studies could use this distance as a tool for finding ways to better understand the origin of male reproductive problems.
‘‘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. This distance could also be used in future studies as a tool to gain insight into a time in foetal life that is impossible to study in humans. Say a clinician were to examine a 30-year-old man with testicular cancer - previously there would have been no way of knowing what hormones he was exposed to in the womb. We would suggest that this measurement, even at this later stage in life, 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. '' Dr Welsh concluded.
To listen to an interview with Dr Michelle Welsh visit the MRC podcast webpage.
Original research paper: Identification of a programming window for reproductive tract masculinization and origin of hypospadias and crytorchidism is published online in the Journal of Clinical Investigation.
• Hypospadias occurs in 0.4% to 1% of boys at birth
• Cryptorchidism occurs in 2.4% to 9% of boys before they are one year old
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