Male reproductive health problems could begin in the womb

Disruptions to male babies’ development early during pregnancy could have a profound effect on a man’s future reproductive health, according to new research.

Professor Kate Loveland and PhD Student, Penny Whiley, research into new insights that potential causes male reproductive health problems later in life.

A world-first finding into the gestation period when testes develop in the fetus has given researchers new insights into the potential causes of male infertility and testicular cancer later in life.

A Hudson Institute research team led by Professor Kate Loveland has discovered that a growth factor, activin A, is linked to steroid production in the testes in utero.

“This research demonstrates for the first time that activin A is necessary for normal production of testosterone in the fetal testis,” said Penny Whiley, a PhD student with the Testis Development and Male Germ Cell Biology group and the study’s first author.

Published in the journal Endocrinology, the discovery shows that activin A promotes synthesis of two enzymes crucial for the final steps of testosterone synthesis, in a preclinical model. However, the absence of activin A resulted in an abnormal steroid environment.

Ms Whiley said the findings pinpoint an important growth period in utero when the testes are developing.

“Events that alter activin A levels, which can occur due to different physiological conditions of pregnancy or the mother’s exposure to certain medications, may explain why some boys and men have impaired reproductive health,” Prof Loveland said.

“Testicular cancer is the second most common cancer in young men aged 18-39. Reduced fertility affects one in 20 men. Both are increasingly common, but the causes of these disorders are not well understood. Disruptions occurring during fetal life may have a profound effect on a man’s future reproductive health,” she said.

The research provides a new understanding of how steroids are produced in the fetal testis. In addition, the key role of activin A highlights how formation of the earliest germline cells may be affected by factors in their environment.

“This study is part of our ongoing research that aims to better understand the basis of male infertility and conditions such as hypospadias, cryptorchidism (see Key facts below) and testicular cancer, which are increasing worldwide,” Prof Loveland said.

Key facts

  • Reduced fertility affects one in 20 men
  • Testicular cancer is the second most common cancer in 18-39-year-old men
  • Hypospadias and cryptorchidism are part of a group of disorders known as Testicular Dysgenesis Syndrome.
  • Hypospadias is a condition in which the opening of the urethra is on the underside of the penis instead of at the tip.
  • Cryptorchidism is when one or both testes fail to descend from the abdomen into the scrotum.

Funders | NHMRC

Collaborators | Professor David Handelsman (ANZAC Institute, Sydney, AUS), Professor Kristian Almstrup (Copenhagen University Hospital)

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