Sperm Decline In Quality With Age Just As Eggs Do

Scientists are finally focusing on fathers’ ages to determine consequences for fertility, pregnancy, and child health.

By Yasemin Isbilir

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When TikToker @yuniquethoughts sat down and opened her Notes app to start writing, she did not plan to go viral. What began as a silly list of her reasons not to have kids, ballooned into hundreds of people stitching her original video and adding their own experiences, horror stories, and warnings about what can happen to the body during pregnancy and birth.

This communal digital diary of pregnancy’s dark side, with more than 350 reasons not to have kids, highlights how the life quality of the mother is affected. Items on the list sound like nightmares, from tooth sensitivity and morning sickness to bones separating and nipples detaching. When it comes to reproduction itself, nearly every risk and burden is placed on the child-bearing individual.

To ensure the well-being of the baby, mothers are expected to follow countless recommendations. The American College of Obstetricians and Gynecologists publishes prenatal guidelines with restrictions on caffeine, certain cheeses, and instructions about sleep positions, supplements, lifestyle choices, vaccinations, and travel. The best-selling guide What to Expect When You’re Expecting has grown to over 600 pages, also reflecting just how extensive the expectations have become.

Yet someone is missing from all these instructions: the father. Science is increasingly finding that fathers influence a woman’s ability to conceive, the health of the child, and even the health of the mother during the postpartum period. The most important of these factors is age.

Delayed Fatherhood

Anne Goriely, PhD, a professor of Human Genetics at the Radcliffe Department of Medicine in the University of Oxford, is one of the few scientists who is uncovering how a fathers age affects genetic health of the children. Her work focuses on the origins of certain mutations and the mechanisms that cause them to increase with age.

“I’m hoping people will come to realize it is not always the mother’s fault,” Goriely says. “Both parents share more than just half their genome, you need to also share risk. The debate about who’s responsible when things don’t go well should change slightly.”

The increasing attention to this topic is due to demographic changes in fatherhood. Delayed fatherhood and increasing paternal ages have become more common in the past few decades. According to a study from Stanford Medicine, which looked at 170 million American birth records from the past four decades, the average age of a new American father has surpassed 30, and the percentage of dads over 40 has doubled. In 1980, the average new father was around 27 years old, making today’s average a noticeable shift upward.

One explanation for increasing paternal age is simply that humans are living longer. Older generations had different expectations around when to have children, and parenthood later in life was not as common. People can spend more years building careers, in higher education, or waiting for financial stability which can push fatherhood back. As family timelines shift, the question of what to consider when planning to have a baby is reforming.

Scientists have long observed that older parents tend to have children with more health problems. For decades the default explanation focused on maternal biology, and few long-term studies existed to study the effects of paternal age as a meaningful variable.

Public awareness has remained low as a result, and many people are still unfamiliar with how a father’s health shapes conception or pregnancy. But as genome-sequencing technologies advanced, which allowed researchers to pinpoint where new genetic mutations come from, the tools to look at paternal contributions with precision expanded.

Father’s Biological Age Matters

Most people think of mutations as random copying errors, like typos that increase with age. Yet some mutations are not linear with age, but exponential with age within the testes. De novo mutations are genetic changes that happen spontaneously rather than mutations that are inherited. Previously they have been difficult to study.

However, the Human Genome Project, which ended in 2003, was the first time the entire human genome was completely sequenced. A genome is the entire set of genetic information of an organism. Because of the human genome project and the development of next generation sequencing, it is now possible to study a child’s unique genetic variations from the generation prior. These new technologies that have only been available for the past two decades are allowing for de novo mutations to be identified more readily by comparing a child’s genome to their parents.

A 2023 review in Genes that synthesized decades of fertility and genetics research also found that sperm quality declines not simply in count but in integrity with age. Older sperm are more likely to carry accumulated replication errors, chromosomal abnormalities, and fragmented DNA.

DNA fragmentation, which is a type of male fertility test that measures the DNA damage present in a sample of sperm, had an interesting finding. While all men had some amount of damage in their sperm DNA, men over 45 had more than double the DNA fragmentation index of men under 30.

The consequences for pregnancy are clear. DNA fragmentation is associated with longer time to conception, increased miscarriage risk, and poor outcomes in early embryonic development, even when sperm count remains the same and conception occurs without difficulty.

Part of the societal neglect comes from the biological fact that sperm production does not stop at a specific age. This has contributed to the myth that male fertility is uncomplicated and endless. However, assuming that the father matters less because men do not experience a discrete fertility cutoff the way women do with menopause gives a false sense of simplicity and misrepresents the father’s role in child development.

Because sperm are produced continuously across a lifetime, the male germline, the cells that form sperm, undergo hundreds of additional cell divisions compared to eggs. By 50, a man’s sperm producing cells have replicated more than five times as often as they had by age 20, meaning the opportunity for replication errors have increased substantially.

Large sequencing studies have shown that the number of new mutations passed to a child rises by two base pairs per year of paternal age. So, while the individual risk to any single child remains low, this cumulative effect becomes significant on the population level.

“We’ve come to realize that the vast majority of de novo mutations are paternal in origin,” Goriely said. “And that’s just due entirely to the process of spermatogenesis.” Spermatogenesis is the biological process of creating sperm cells. Goriely is best known for discovering “selfish spermatogonial selection,” a process where rare mutations in the male germline expand clonally within the testes with age.

Older Parents and Children’s Health

De novo mutations can heavily increase the risk of transmitting genetic disorders like Apert syndrome, Costello syndrome, and achondroplasia. Goriely’s work clearly links paternal age to the health of future generations.

Genes that control cells in testes are also expressed in organs like the brain that play important roles in brain function and development. So, while the selfish selection mechanism has so far only been demonstrated in rare conditions, there is still a need for attention. There is the possibility that these mutations are associated with neurodevelopmental disorders such as autism.

Neurodevelopmental implications of paternal age is where the interests of Julianne Zweifel, PhD, a psychologist at the University of Wisconsin School of Medicine and Public Health in the Department of Obstetrics and Gynecology lie.

In her 2022 review posted in Fertility and Sterility, Zweifel and her colleagues found evidence linking advanced paternal age with increased rates of ADHD, autism, bipolar disorder, and other neurodevelopmental outcomes. As a clinician that has served on the ethics community for the American Society of Reproductive Medicine, she considers age in patients pursuing assisted reproduction.

Zweifel believes that there is another layer of risk that extends past the genetics conversation that affects families in ways many studies cannot explain. Parental death is a major concern amongst children of older parents. Adults raised by older parents often describe a childhood marked by worry where they are constantly looking for signs that their parents’ health is declining. These lived experiences, she argues, must be part of the conversation. Zweifel is in favor of guidelines being placed in reproductive clinics.

“Men, in general, are not accustomed to institutions limiting them, whereas women have historically had a lot of limitations,” Zweifel says. “To even begin to discuss placing limits on male reproduction is a pretty provocative thing because people have the right to reproduce. So, it’s not without limits, anytime you’re putting constraints on something like that, it needs to be very thoughtful.”

Both Parents’ Age Matters

Researchers like Zweifel and Goriely are careful to distinguish population and individual level risk. For most families the risk remains low, but across a society, the trend towards later fatherhood matters.

“You want people to be able to be free to make decisions and be supported in what they want to do. The ability of understanding mutations gives you an ability to help people,” Goriely says. Whether that means offering better preconception counseling or helping families make more informed decisions after having an affected child, she believes that knowledge is power.

Ying Meng, PhD, an associate professor at the University of Rochester, is also helping bring more scrutiny to the table. In a study of 36,000 births, Meng and her team found that increasing paternal age is correlated with increasing levels of preterm birth and low birthweight, which are among the major causes of infant mortality. But Meng feels that age does not act alone.

“Age, race and ethnicity, and education are all linked to socioeconomic aspects,” Meng says. “When the partner’s age is older, they may also have a more stabilized income and better health insurance. So, we need to understand how the father’s genetic contribution and the social environment interact. Each family is different, and we should always acknowledge that.”

Similarly, a study published in Reproductive Biology and Endocrinology in 2015, Sharma and colleagues from the Cleveland Clinic Center for Reproductive Medicine and various research institutions in Saudi Arabia, found that as men age sperm accrues epigenetic changes that increases the risk for miscarriage and early birth. This is not to say that late fatherhood is dangerous or inherently irresponsible, but that paternal health and age need to be discussed in the same way it is for mothers.

While the importance of the father in a child’s social and emotional development is being widely accepted, the idea that the father plays a role before conception is not. We need to incorporate paternal health into preconception counseling and public health education so that men receive the same evidence-based guidance that women do and are encouraged to be active participants in the process of parenthood.

A 2017 review on men’s attitudes and education around fertility, published in the journal Human Reproductive Update, found that there is a lack of knowledge about the factors that can influence conception. This is due to the fact that the preconception period is acknowledged as an important window in planning for parenthood but has previously centered mostly on the decisions and choices women should make.

Men across high-income countries overwhelmingly valued parenthood, expected to become fathers someday, and aspired to have at least two children. Yet, most had limited understanding of both male and female fertility, and frequently overestimated their likelihood of spontaneous conception and the success rates of assisted reproduction.

The review also highlighted a gap between the biologically optimal time to conceive and the socially ideal conditions men believe they need before becoming fathers such as a stable relationship, financial security, and personal maturity. As social milestones occur later in life, the window for achieving parenthood narrows. This adds an extra dimension to why paternal factors are central to reproductive conversations.

Accumulating research shows that paternal factors can influence long term outcomes in child health and development. They challenge current assumptions about who shapes the health trajectory of future generations. A comprehensive model of reproductive care includes both parents and starts with more encompassing fertility education and preconception care that puts pressure on men.