Exposure of a male fetus to abnormal levels of a growth factor present during pregnancy has now been shown to directly affect development of a male baby’s sperm cells, which could lead to infertility and testicular cancer later in life.
For the first time, Hudson Institute researchers Dr Sarah Moody and Professor Kate Loveland have demonstrated that high levels of the growth factor protein, activin A, may act directly to affect the development of sperm precursor cells (cells in a male fetus’ testis which will eventually become mature sperm). Around 90 to 95 per cent of testicular cancers start in these sperm precursor cells.
Correct development of these cells during pregnancy is vital for producing normal, healthy sperm in adult life. When activin A levels in the mother are high, disruptions to the sperm development processes in the womb can lead to later male reproductive disorders, including infertility and testicular cancer. Activin A levels may be elevated in some pregnant women who take certain medications such as selective serotonin reuptake inhibitors (SSRIs), have infections, or suffer from conditions such as pre-eclampsia.
“Activin A is normally produced and acts throughout the body. This study shows high levels within the testis may have lifelong consequences if exposure occurs at a vulnerable stage of development,” says Prof Loveland.
Another piece of the puzzle
Using a human cell line model, the team’s research published in Reproduction, showed activin A can act directly on human sperm precursor cells to affect their fate, a key addition to other work from Prof Loveland’s lab that demonstrates its actions are central to creating a healthy testis and sperm.
“Our findings shed light on the complex puzzle of how physiological changes in a pregnant woman can affect the future fertility and health of her male child,” says Dr Moody.
“With rates of infertility and testicular cancer increasing around the world, the more information we have, the better chance we will have for developing treatments or minimising risk due to exposures during pregnancy.”
Dr Moody suggests, for example, that her discovery may inform future management of prescription medication and epidemiological studies.
The next step for the team is to use preclinical models to further explore the direct and indirect impact activin A can have on sperm precursor cell development.
- Infertility now affects roughly one in six couples in Australia, with a male factor contributing to half of all cases
- Fertility problems can cause significant emotional and psychological distress for a couple
- Testicular cancer is the second most common cancer in young men (aged 18 to 39)
- About 90-95% of testicular cancers start in the sperm precursor cells
- The incidence of testicular cancer is rising worldwide at 2% per year, for unknown reasons
- While recovery rates from testicular cancer are excellent, it can still have life-long consequences
Patrick Western, Shoichi Wakitani, Julia Young (our co-authors)
NHMRC Ideas Grant and fellowship, Victorian State Government Operational Infrastructure Scheme, Australian Government RTP scholarship, Japan Society for the Promotion of Science.