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Male infertility and somatic health — insights into lipid damage as a mechanistic link

Abstract

Over the past decade, mounting evidence has shown an alarming association between male subfertility and poor somatic health, with substantial evidence supporting the increased incidence of oncological disease, cardiovascular disease, metabolic disorders and autoimmune diseases in men who have previously received a subfertility diagnosis. This paradigm is concerning, but might also provide a novel window for a crucial health reform in which the infertile phenotype could serve as an indication of potential pathological conditions. One of the major limiting factors in this association is the poor understanding of the molecular features that link infertility with comorbidities across the life course. Enzymes involved in the lipid oxidation process might provide novel clues to reconcile the mechanistic basis of infertility with incident pathological conditions. Building research capacity in this area is essential to enhance the early detection of disease states and provide crucial information about the disease risk of offspring conceived through assisted reproduction.

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Fig. 1: Incident comorbidities of male infertility and the role of lipid oxidation.
Fig. 2: Male infertility, incident comorbidities and lipid oxidation.
Fig. 3: Biosynthesis of oxidized phospholipids by ALOX15 and consequences for human health and fertility.
Fig. 4: Lipid damage as a molecular link between male infertility and somatic health.

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Acknowledgements

The authors gratefully acknowledge the research contributions of all laboratories working on the ‘canary in the coal mine — male reproductive health’ paradigm and M. O’Bryan for bringing this issue to the attention of the Society for Reproductive Biology (SRB), Australia and New Zealand. The authors also acknowledge the work of the Male Reproductive Health Initiative of the European Society of Human Reproduction and Embryology. The authors acknowledge funding from the National Health and Medical Research Council (NHMRC), Australia, awarded to B.N., E.G.B. and R.J.A. (APP1163319).

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E.G.B., N.D.B. and R.J.A. researched data for the article. E.G.B., N.D.B., B.N., S.D.R., J.E.S. and J.L.H.W contributed substantially to discussion of the content. E.G.B. and N.D.B. wrote the article. All authors reviewed and edited the manuscript before submission.

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Correspondence to Elizabeth G. Bromfield.

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Burke, N.D., Nixon, B., Roman, S.D. et al. Male infertility and somatic health — insights into lipid damage as a mechanistic link. Nat Rev Urol 19, 727–750 (2022). https://doi.org/10.1038/s41585-022-00640-y

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