• Elena Zambrano, Peter W Nathanielsz, and Guadalupe L Rodríguez-González.
• Reproductive Biology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, México.
• Eur. J. Clin. Invest. 2021 Oct 1; 51 (10): e13637.

AbstractDevelopmental programming predisposes offspring to metabolic, behavioural and reproductive dysfunction in adult life. Evidence is accumulating that ageing phenotype and longevity are in part developmentally programmed in each individual. Unfortunately, there are few studies addressing the effects of developmental programming by maternal nutrition on the rate of ageing of the male reproductive system. This review will discuss effects of foetal exposure to maternal environmental challenges on male offspring fertility and normal ageing of the male reproductive system. We focus on several key factors involved in reproductive ageing such as decreased hormone production, DNA fragmentation, oxidative stress, telomere shortening, epigenetics, maternal lifestyle and nutrition. There is compelling evidence that ageing of the male reproductive system is developmentally programmed. Both maternal over- or undernutrition accelerate ageing of male offspring reproductive function through similar mechanisms such as decreased serum testosterone levels, increase in oxidative stress biomarkers in both the testes and sperm and changes in sperm quality. Importantly, even in adult life, exercise in male offspring of obese mothers improves adverse effects of programming on reproductive function. Maternal consumption of a low-protein diet causes transgenerational effects in progeny via the paternal line. The seminal fluid has effects on the intrauterine environment. Programming by male factors may involve more than just the sperm. Improving knowledge on developmental programming ageing interactions will improve not only male health and life span but also the health of future generations by reducing programming via the paternal line.© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

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