The World Health Organization defines infertility as a disease of the male or female reproductive system if 12 or more months of unprotected sex does not result in pregnancy.

What does that mean from a cellular perspective? During a specific type of cell division called meiosis, each diploid cell (containing two chromosome sets—one from mom and one from dad) undergoes two rounds of cell division to create four haploid cells called gametes, also known as the sex cells, or the egg and the sperm.

Each egg or sperm cell has 23 chromosomes, or one chromosome set. When an egg and sperm combine during fertilization, the fertilized egg has 46 chromosomes, meaning that all the genetic information is present for proper development. But an error in meiosis may lead to infertility for both men and women.

The answer is, yes, all of the above affect infertility. Genes certainly play a role. We know that approximately 7% of the male population is infertile due to physiological defects, sperm production, or unknown genetic origins. Similarly, about 10% of women are infertile; physiological defects, X chromosome abnormalities, additional chromosome errors, and other factors may be responsible.

Age is important as well. As a woman ages, cellular and molecular function for egg quality invariably and exponentially drops around age 35 to 40. Although male sperm production proceeds continuously throughout a man’s adult life, new evidence is emerging that may involve declines in sperm quantity and quality with age.

Environmental risk factors affect, well, everyone. Well known contributors include DNA-damaging diagnostic imaging and radiation therapies, alcohol and tobacco consumption, poor diet, and physical inactivity. In addition, certain chemicals common in water bottles, food packaging, and other products used daily like household cleaning supplies and even shampoo can disrupt hormones required for reproductive health.

Around 2,000 genes have been identified as participants in male reproductive process of forming sperm, or spermatogenesis. At the onset of puberty, sperm are constantly produced by continuously completing both phases of meiosis within weeks.

The female reproductive process of forming eggs, or oogenesis is markedly different and begins in utero. Egg cells enter initial meiosis before stopping at the start of the first metaphase, where replicated chromosome pairs align in preparation for separation. At puberty, hormones are generated that periodically resume meiosis with typically one follicle completing meiosis each month. This enveloped cell begins the second meiosis, or meiosis II, before halting after ovarian release. Meiosis II only resumes if the egg is fertilized by a sperm cell.

A woman typically begins her reproductive years with 400,000 eggs. While we know that the number of eggs decreases as a woman ages, scientists are also researching the quality of the eggs with respect to ages, and how that may lead to an increased risk of infertility, miscarriage, and potential birth defects.

Stowers Investigator Jennifer Gerton, Ph.D., researches causes of cellular decline that indicate quality and not quantity of eggs are the primary perpetrator. A major factor is aneuploidy, or the incorrect segregation of chromosomes during meiosis, resulting in mature eggs with the wrong number of chromosomes.

Additional factors include declines in mitochondrial function, the energy-producing cellular machines, along with protein metabolism and proteins involved in chromosome segregation. Studies indicate that the biologic age of eggs is the prime determinant of egg quality and a successful reproductive outcome.

From an evolutionary perspective, the many phases of meiosis have been conserved. For embryos that are fertilized, between 10% to 25% do not have the correct quantity of chromosomes, with more than 80% of these resulting from improper chromosome segregation during female meiosis I.

Stowers Associate Investigator SaraH Zanders, Ph.D., focuses on understanding selfish genes which bias their transmission to more than half of offspring. A specific type of selfish gene called killer meiotic drivers are not only overrepresented in the next generation but also kill offspring that do not inherit the gene. This can eventually result in a population with decreased fitness and fertility.

Globally, people are choosing to delay having children for myriad motivations. While a woman’s reproductive function steeply drops off beginning in mid to late thirties, there is growing evidence that male reproduction is also prone to performance reductions. Stowers Investigator Scott Hawley, Ph.D., studies the molecular mechanisms involved in meiosis to gain insight into infertility.

The Gerton Lab is researching female reproductive aging, looking at how cellular and molecular factors associated with age-related deterioration may eventually lead of ways to delay aging and improve women’s health overall.