Hypospadias: A congenital anomaly of the penis on the rise, why?


This team of pediatricians and geneticists from Washington State University wondered about the growing prevalence of this congenital anomaly of the penis, hypospadias, characterized by the opening of the urethra on the inside of the penis (instead of its end). The study, published in Scientific Reports, invokes environmental factors, which lead to epigenetic changes, in the developing penis.

genital malformation in male babies:

The research is motivated by the authors' observation, in clinical practice, of an alarming increase in the incidence of this genital malformation in male babies. Epidemiological data show that the prevalence of hypospadias has increased by 11.5% in recent decades, making it the most common genital malformation in newborn boys.
Environmental factors, such as exposure to toxic substances have already been mentioned.

hypospadias causes:

The study of tissue samples of hypospadias finds:
  • the absence of genetic mutations of DNA sequences correlated with the presence of the disease;
  • but the presence of specific epigenetic alterations. The authors recall that these epigenetic modifications around the DNA do not modify the DNA but modify their expression;
  • these same epigenetic alterations are not found in penile tissue samples taken from the foreskin of babies without hypospadias;
  • finally, tissue samples with mild hypospadias show a greater degree of epigenetic alterations than tissue samples with severe hypospadias: this surprising result can be explained by the fact that cells with very severe epigenetic alterations do not survive.

These observations help to explain this increased incidence and the possible causes of hypospadias: the principal author, Dr. Michael Skinner, professor of biology concludes that "the etiology of the disease is dictated by the environment and epigenetics rather than by mutations or genetic susceptibilities”.

Towards earlier detection?

These data suggest the possibility of this, as well as better clinical management of hypospadias, by targeting a specific epigenetic biomarker that could be collected with a simple buccal swab from a baby's parents to determine the likelihood that the new -born develops the malformation. Such biomarkers have already been identified for other diseases. Their early detection allows for earlier clinical management which means fewer complications for the baby and more peace of mind for the parents.

Behind these epigenetic alterations, what environmental factors?

In other words, what are the toxic substances whose exposure could promote these epigenetic modifications at the origin of hypospadias? One culprit mentioned by researchers may be diethylstilbestrol (Distilbene or DES), a drug used in the late 1950s to ease the later stages of pregnancy in women.

“Because the epigenetic changes caused by drugs like this and other environmental toxicants are epigenetically inherited, they are often passed on from one generation to the next after being contracted. Over time, the adverse effects may linger and spread.”