Poor diet may worsen genetic causes of male infertility, study finds

Lifestyle factors can worsen the effects of genetic causes of male infertility, finds new research that could help explain why men carrying similar genetic mutations often experience different levels of fertility impairment.

The proof-of-concept study, published in Human Reproduction, and led by University of Melbourne researchers Dr Jessica Dunleavy and Professor Moira O’Bryan from the School of BioSciences, used a mouse model carrying defects in a gene called M1AP. Mutations in M1AP are a relatively common cause of male infertility in humans but not all men are affected equally.

Researchers investigated if the consequences of the genetic change could be worsened when mice were fed with an unhealthy Western-style diet, high in fat and sugar.

The team found that both the genetic change and the Western diet independently reduced fertility. However, when combined, fertility outcomes were substantially worse than with either factor alone.

Specifically, mice which experienced both the genetic and environmental challenge produced fewer offspring, and their sperm was of a lower quality than mice exposed to either the genetic or dietary challenge alone.

The researchers say this proof-of-principal study provides evidence that some male infertility cases may result from a combination of genetic and lifestyle factors, rather than either acting in isolation. In some cases, this would be predicted to push fertility to a level below the ‘threshold’ for natural conception.

M1AP ‘variants’ (or mutations) are among the more commonly known genetic causes of male infertility but not all men are affected equally.

Men carrying damaging variants in this gene experience a spectrum of infertility presentations, ranging from very low sperm counts to the complete absence of sperm. The reasons for this variability are not fully understood, but these new findings may shed new insight.

"Our study suggests that environmental or lifestyle factors, such as diet, may contribute to those differences in disease severity," Dr Dunleavy said.

"While genetics may establish a reduced baseline of fertility and a predisposition to infertility, lifestyle factors likely influence how severe the infertility is, and ultimately the capacity to father children. If true, we predict that improving diet or environmental exposures may improve fertility."

A similar situation would be predicted for many other genes that play a role in male infertility, the researchers say.

The researchers stress that the study was conducted in mice and further research is needed to determine whether similar interactions occur in humans. The study provides an important foundation for future research investigating how lifestyle factors contribute to infertility and if interventions could help improve reproductive outcomes in men with underlying genetic susceptibility to infertility.

"Our findings highlight the importance of considering both genetic and lifestyle factors when investigating the causes of male infertility," Professor O’Bryan, who is also the Dean of Science, said.

"Ultimately, understanding these interactions will support a more personalised approach to fertility care in the future."

Reference:

Brendan J Houston, Joseph Nguyen, Nadja Rotte, Frank Tüttelmann, Corinna Friedrich, D Jo Merriner, Anne E O’Connor, Moira K O’Bryan, Jessica E M Dunleavy, A Western-style diet exacerbates male infertility in M1ap knockout mice, Human Reproduction, 2026;, deag130, https://doi.org/10.1093/humrep/deag130