A significant review released today in Nature Ageing uncovers novel genetic connections among reproductive health, fertility, and life expectancy. Researchers from the University of Oxford and the University of Iceland emphasised the influence of DNA shape variations on reproductive traits and their implications for broader health outcomes, including ageing, cancer risk, and obesity, in their study.

This detailed examination reviewed 159 genetic studies, pinpointing 37 significant genes that affect traits such as menopause timing, age at first childbirth, and hormonal regulation. The study provides essential insights into the influence of our genes on fertility windows, longevity, and health across generations, particularly as more individuals choose to delay parenthood.

The researchers examined the GWAS Catalogue, a comprehensive database of Genome-Wide Association Studies, to identify genes linked to important reproductive traits. The analysis uncovered a significant correlation between the FSHB gene (follicle-stimulating hormone subunit beta) and 11 distinct reproductive outcomes. This gene plays a crucial role in regulating the timing of menstruation and menopause, underscoring its significance in both reproductive health and the ageing process.

Professor Melinda Mills, the senior lead author from the Leverhulme Centre for Demographic Science, stated, “With an increasing number of individuals postponing parenthood to later ages, it is crucial to comprehend the genetic factors that influence an individual’s reproductive health and fertility window.”

The study extended its findings beyond fertility, uncovering notable correlations between reproductive genes and rare genetic disorders, thereby highlighting the influence of our DNA on overall health.

The study reveals a compelling relationship between reproductive genes and longevity. For instance, researchers have identified the gene ESR1 (oestrogen receptor 1) as a factor that influences both reproductive traits and cancer risk. The onset of puberty at an earlier age or the occurrence of menopause at a later stage may be associated with an extended lifespan; however, these characteristics also heighten the risk of developing hormone-sensitive cancers, including breast cancer.

The researchers conducted an examination of the FTO gene, which has been extensively associated with BMI, obesity risk, and type 2 diabetes. The research indicated that FTO has an impact on reproductive traits, revealing a distinct intersection between the genetic pathways that regulate fertility and those associated with metabolic health.

Dr. Stefanía Benónísdóttir, the study’s first author, stated, “By consolidating this research, we provide a more precise understanding of the ways in which genetic factors influence reproductive health.” This is crucial for the progression of healthcare, particularly regarding infertility and reproductive ageing.

This study expands the existing body of research on reproduction by also examining the genetic factors influencing male fertility, an area that has received comparatively less attention. The association of genes such as DNAH2 with testosterone levels and sperm function provides significant insights into the intricacies of male reproductive health.

Co-author Vincent Straub highlighted the significance of this finding: “Male reproductive health is essential to overall fertility but frequently overlooked in research.” Investigating the genetics of male infertility allows for the discovery of new insights and potential treatments for individuals facing reproductive challenges.

The review examined the impact of genetic changes, especially those originating from older parents, on subsequent generations. Individuals accumulate "de novo mutations" as they age, transmitting new, spontaneous genetic alterations to their offspring. Senior co-author Professor Augustine Kong has thoroughly examined how these mutations can significantly influence the health and development of children.

This review highlights the growing significance of personalized healthcare.  Understanding the genetic factors that influence reproductive health allows healthcare providers to create targeted interventions aimed at enhancing fertility outcomes, postponing ageing, and addressing related health risks.

Professor Mills elucidated that the relationships among reproductive genes, longevity, and overall health underscore the intricate dynamics between our biological makeup and the choices we make throughout our lives. Genetic insights may facilitate the prediction of individual fertility windows, the identification of risk factors for hormone-sensitive cancers, and the formulation of lifestyle adjustments aimed at optimizing reproductive and long-term health.

The research establishes a robust basis for subsequent investigations into the genetic factors influencing fertility, ageing, and health. As reproductive behaviors evolve in contemporary societies, it is essential to analyze DNA's role in shaping these traits to effectively tackle fertility issues and enhance overall health and longevity.

The researchers highlight that these findings represent merely the initial phase. Through ongoing examination of the genetic connections between reproduction and health, the goal is to reveal additional avenues for enhancing healthcare results across generations.