How DNA shapes reproductive health, fertility and even life expectancy

Led by researchers from the University of Oxford’s Leverhulme Center for Demographic Science and the University of Iceland, a review published in Nature agingexamines how genetic variations can explain differences in reproductive health and lifespan.

The study provides the most comprehensive overview of male and female genetic discoveries of reproductive traits to date, offering new insights into how our DNA influences childbearing, the timing of menopause, and even how that relates to how long we live to live.

Genes are at the heart of reproduction

Using the GWAS cataloguean online Genome Wide Association Studies (GWAS) database, the researchers identified 159 genetic studies and 37 key genes associated with reproductive characteristics such as age at first childbirth, timing of menopause and hormones such as follicle-stimulating hormone (FSH). and testosterone.

These findings suggest that genetic factors play an important role in broader health outcomes and also influence 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 links between these reproductive genes and rare genetic disorders, showing how DNA influences both fertility and overall health.

Senior lead author Professor Melinda Mills, Director of the Leverhulme Center for Demographic Science and Oxford Population Health’s Demographic Science Unit said: “As more people postpone parenthood until later ages, it is important to understand the genetic factors underlying the reproductive health and fertility of an individual.

“Our study brings together research into the genetics of reproduction to reveal common genes about traits and insights beyond fertility and 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 Center for Demographic Science and the University of Iceland, said: “By consolidating this research, we provide 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 characteristics

The review examined the links between reproductive genes and longevity, finding that genes such as ESR1 (estrogen receptor 1) are linked to both reproductive traits and cancer risk. For example, starting puberty earlier or entering menopause later may increase your risk for hormone-sensitive cancers such as breast cancer, but these same traits are associated with 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 several different reproductive traits. Understanding these genetic links is critical as more and more people choose to delay having children, making reproductive health and aging even more closely intertwined.

Male fertility

While previous research focused on women’s reproductive health, the study reviews what is known about the genetics of male fertility. Genes like DNAH2 have been shown to play a role in both testosterone levels and sperm function, making it crucial for men’s reproductive health.

Co-author Vincent Straub, DPhil student at the Leverhulme Center for Demographic Science and Oxford Population Health, said: “Men’s reproductive health is critical to overall fertility, but is often under-researched. The genetics of male infertility research, we may discover new insights and possible treatments for people struggling with reproductive problems.”

Genetics across generations

The review examined how genetic changes affect future generations. As parents grow older, they accumulate de novo mutations: new, spontaneous genetic changes that can be passed on to their children.

These mutations can have significant consequences for the health and development of offspring, discovered earlier by senior co-author Professor Augustine Kong.

This comprehensive review provides 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.