Researchers revealed genetic links between reproductive health, fertility, and longevity, emphasizing their impact on overall health.
Researchers from the University of Oxford’s Leverhulme Centre for Demographic Science and the University of Iceland conducted a comprehensive review investigating how genetic variations influence reproductive health and longevity.
This study represents the most thorough examination of male and female genetic discoveries related to reproductive traits to date. It sheds new light on how our DNA impacts key life events, such as the age at which individuals have children, the timing of menopause, and the links between these factors and lifespan.
Genes at the heart of reproduction
Using the GWAS Catalog, an online database of Genome Wide Association Studies (GWAS), the researchers identified 159 genetic studies and 37 key genes that are linked to reproductive traits such as age at first childbirth, menopause timing, and hormones such as follicle-stimulating hormone (FSH) and testosterone. These findings suggest that genetic factors play a significant role in broader health outcomes as well as influencing fertility.
One gene in particular, FSHB (follicle-stimulating hormone subunit beta), was found to be associated with eleven different reproductive outcomes. This gene helps regulate when menstruation begins and when menopause occurs, highlighting its role in reproductive health and aging. The review also revealed connections between these reproductive genes and rare genetic disorders, showcasing how DNA impacts both fertility and overall health.
Senior lead author Professor Melinda Mills, Director of the Leverhulme Centre for Demographic Science and Oxford Population Health’s Demographic Science Unit said, “As more people delay parenthood to later ages, it is important to understand the genetic factors underpinning an individual’s reproductive health and fertility window. Our study brings together research on the genetics of reproduction to reveal common genes across traits and insights beyond fertility that are inherently linked to health, body mass index (BMI) and obesity, hormone-sensitive cancers, and even psychiatric and behavioral traits.”
First author Dr Stefanía Benónísdóttir, Postdoctoral Researcher at the Leverhulme Centre for Demographic Science and University of Iceland, said, “By consolidating this research, we offer a clearer picture of how genetic factors shape reproductive health. This is essential for advancing healthcare, especially when it comes to infertility and reproductive aging.”
Longevity, cancer, obesity risk, and reproductive traits
The review explored the connections between reproductive genes and longevity, finding that genes like ESR1 (estrogen receptor 1) are linked to reproductive traits as well as to cancer risk. For example, starting puberty earlier or experiencing later menopause may increase the risk of hormone-sensitive cancers like breast cancer, but these same traits are associated with a longer lifespan.
The FTO (fat mass and obesity-associated) gene – previously found to have strong associations with BMI, obesity risk, and type 2 diabetes – was also linked to multiple different reproductive traits. Understanding these genetic links is critical as more people choose to delay having children, making reproductive health and aging even more intertwined.
Male fertility
While previous research has focused on female reproductive health, the study reviews what is known about the genetics of male fertility. Genes like DNAH2 are shown to play a role in both testosterone levels and sperm function, making it crucial for male reproductive health.
Co-author Vincent Straub, DPhil student at the Leverhulme Centre for Demographic Science and Oxford Population Health, said “Male reproductive health is critical to overall fertility but often under-researched. By exploring the genetics of male infertility, we can uncover new insights and potential treatments for those struggling with reproductive challenges.”
Genetics across generations
The review examined how genetic changes affect future generations. As parents age, they accumulate de novo mutations – new, spontaneous genetic changes that can be passed to their children. These mutations can have significant effects on the health and development of offspring, previously discovered by senior co-author Professor Augustine Kong.
This comprehensive review offers crucial insights into how our genes shape reproductive health, fertility, and longevity, providing a foundation for more personalized healthcare approaches that could improve outcomes for individuals and families across generations.
Reference: “Genetics of female and male reproductive traits and their relationship with health, longevity and consequences for offspring” by Stefania Benonisdottir, Vincent J. Straub, Augustine Kong and Melinda C. Mills, 13 December 2024, Nature Aging.
DOI: 10.1038/s43587-024-00733-w
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