Research led by Johns Hopkins University shows some women may carry genetic variants that increase their risk for pregnancy loss.
As reported in Nature, the team showed that genetic variation that impacted the way egg cells divide during meiosis influenced the number of embryos with abnormal numbers of chromosomes.
“Despite their critical role in encoding genetic information, chromosomes frequently mis-segregate during human meiosis, producing abnormalities in chromosome number—a phenomenon termed aneuploidy,” explain lead author Rajiv McCoy, PhD, a Johns Hopkins computational biologist focused on the genetics of human reproduction, and colleagues.
“Aneuploidy is the leading cause of human pregnancy loss, as well as the cause of genetic conditions such as Klinefelter, Turner and Down syndromes.”
The study analyzed data from 139,416 in vitro fertilized (IVF) embryos plus DNA from 22,850 parental pairs to look at genetic causes of aneuploidy-linked miscarriage and survivable aneuploidies like those seen in Down syndrome.
McCoy and colleagues found that embryos with aneuploidies are very common. They also showed this problem comes mostly from the egg rather than the sperm and increases with the mother’s age. Chromosomes 15, 16, 21 and 22 were affected more often than others.
The team noted that embryos with aneuploidies had less evidence of genetic recombination, an important mixing up of genetic information that happens during meiotic cell division, than healthy embryos. Aneuploid embryos had fewer recombination events even on their chromosomes that were present in normal numbers, suggesting that low recombination in an egg increases mis‑segregation risk.
The researchers found a genetic variant that reduces expression of the gene SMC1B and was associated with lower recombination and higher maternal aneuploidy rates. They also found some other genes, C14orf39, CCNB1IP1 and RNF212, linked to meiosis that seemed to influence how likely women were to produce embryos with incorrect numbers of chromosomes.
“This work provides the clearest evidence to date of the molecular pathways through which variable risk of chromosomal errors arises in humans,” said McCoy in a press statement. “These insights deepen our understanding of the earliest stages of human development and open the door for future advances in reproductive genetics and fertility care.”
This work connects common regulatory variation in meiosis genes to real‑world aneuploidy risk in humans, using a uniquely large dataset. It shows risk for aneuploidy is not entirely age‑driven, but is partly shaped by inherited genetic variation. These results need to be confirmed and validated but have potential implications for fertility, reproductive aging, and genetic counseling for women and couples trying to give birth using IVF.
