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Developmental biology - A Father's Contribution|
Dad's Diet Affects Health Of His Kids
Now, new research reveals male mice fed a poor quality diet results in their offspring becoming over weight, with symptoms of type 2 diabetes and reduced gene function regulating their metabolism of fat.
Researchers from the University of Nottingham's Schools of Medicine and Biosciences published their report in PNAS showing that both sperm and ejaculate (seminal plasma) can affect the long-term metabolic health of their offspring.
There is a lot of research showing sperm from men who are overweight, smoke, drink excessively or who have type 2 diabetes - often have poorer quality sperm than healthier men. However, little was known about the impact of such lifestyle factors on the long-term health of his children. A new study bridges this gap by following the long-term growth and metabolic health of offspring from male mice fed a poor quality diet.
According to Adam Watkins PhD, leader of the study and assistant professor in reproductive biology at the University of Nottingham, UK: "It is well understood that what a mother eats during pregnancy can affect the development and health of her child. As such, there is a lot of information available to women who want to become pregnant about the importance of a healthy lifestyle and good dietary choices. Interestingly, little if any advice is available for fathers.
"Our research using mice shows that at the time of conception, diet and well-being of the father influences the long-term growth and metabolic health of his offspring. The study not only identifies what impact a poor paternal diet has on the health of his offspring, but also begins to uncover how these effects get established."
Male mice fed a low-protein diet produced sperm with fewer chemical tags on their DNA needed to regulate how genes function. Researchers also observed that male seminal plasma suppressed a mother's ability to respond with uterine inflammation and other immunological responses essential for maintaining a healthy pregnancy. So researchers now believe the health of offspring is affected by both the quality of a mother and father's genetic information passed on within the sperm and egg at conception, but also by how a father's seminal plasma-primes the uterine environment in which the embryo will develop.
"It is important to recognise that sperm contribute more than just half of the genes that make up a child. During natural conception sperm deposited in the female reproductive tract are bathed in seminal plasma which can in itself influence pregnancy outcome. Our study shows that the composition of seminal plasma can be altered by a father's diet, which can also influence offspring wellbeing."
Parental health and diet at the time of conception determine the development and life-long disease risk of their offspring. While the association between poor maternal diet and offspring health is well established, the underlying mechanisms linking paternal diet with offspring health are poorly defined. Possible programming pathways include changes in testicular and sperm epigenetic regulation and status, seminal plasma composition, and maternal reproductive tract responses regulating early embryo development. In this study, we demonstrate that paternal low-protein diet induces sperm-DNA hypomethylation in conjunction with blunted female reproductive tract embryotrophic, immunological, and vascular remodeling responses. Furthermore, we identify sperm- and seminal plasma-specific programming effects of paternal diet with elevated offspring adiposity, metabolic dysfunction, and altered gut microbiota.
The association between poor paternal diet, perturbed embryonic development, and adult offspring ill health represents a new focus for the Developmental Origins of Health and Disease hypothesis. However, our understanding of the underlying mechanisms remains ill-defined. We have developed a mouse paternal low-protein diet (LPD) model to determine its impact on semen quality, maternal uterine physiology, and adult offspring health. We observed that sperm from LPD-fed male mice displayed global hypomethylation associated with reduced testicular expression of DNA methylation and folate-cycle regulators compared with normal protein diet (NPD) fed males. Furthermore, females mated with LPD males display blunted preimplantation uterine immunological, cell signaling, and vascular remodeling responses compared to controls. These data indicate paternal diet impacts on offspring health through both sperm genomic (epigenetic) and seminal plasma (maternal uterine environment) mechanisms. Extending our model, we defined sperm- and seminal plasma-specific effects on offspring health by combining artificial insemination with vasectomized male mating of dietary-manipulated males. All offspring derived from LPD sperm and/or seminal plasma became heavier with increased adiposity, glucose intolerance, perturbed hepatic gene expression symptomatic of nonalcoholic fatty liver disease, and altered gut bacterial profiles. These data provide insight into programming mechanisms linking poor paternal diet with semen quality and offspring health.
Authors: Adam J. Watkins, Irundika Dias, Heather Tsuro, Danielle Allen, Richard D. Emes, Joanna Moreton, Ray Wilson, Richard J. M. Ingram, and Kevin D. Sinclair.
The authors declare no competing financial interests.
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Male mice fed a low quality diet produced sperm of poorer quality
and a hostile enviornment to fetal development. Image: public domain.