South Middlesex Times

Researchers at Rutgers University-New Brunswick have identified a gene variant associated with early miscarriages in women, potentially advancing the understanding of genetic causes of infertility. The variant is linked to accelerated reproductive aging, resulting in a high number of abnormal eggs that can lead to miscarriages. This discovery could help women anticipate early infertility and guide their reproductive planning and fertility treatments.

"Knowledge of the precise genetic landscape that causes egg abnormalities in women has long been limited," said Karen Schindler, an author of the study and professor in the Department of Genetics at Rutgers School of Arts and Sciences. "This work represents a significant step forward in our understanding of the underlying genetics and provides the deepest validation yet of a candidate variant for causation."

Published in the journal Proceedings of the National Academy of Sciences, researchers identified this variant within the kinesin protein gene KIF18A. It differs from its non-mutated version by only one amino acid but accelerates egg aging in younger women carrying it, reducing their fertility.

Successful female reproduction depends on producing quality eggs. Miscarriages often occur due to aneuploidy—an abnormal number of chromosomes—in eggs, which increases with age. Women with this genetic variant experience more rapid egg aging, leading to higher instances of aneuploidy or "high embryonic aneuploidy."

Rutgers Department of Genetics Professor Jinchuan Xing led a team analyzing genes from women with high embryonic aneuploidy using data from a biobank at an IVF clinic. They found many carried mutations in KIF18A. Studies on mice engineered with this variant showed they produced more abnormal eggs earlier than usual.

"From this, we can say that this is more than a correlation; it's a causal relationship," stated Leelabati Biswas, co-first author and student in Rutgers' joint M.D.-Ph.D. program.

Biswas and Schindler see potential for further discoveries related to aneuploidy variants that could enhance precision medicine for reproductive treatments.

"This is a first step," Biswas remarked. "We're heading in a direction where we may be able to give women more opportunities for precision medicine."

Schindler added that knowing one's genetic risk could influence decisions about when to have children or freeze eggs: "If you know your genetic risk, you will know your outcomes are going to be better if you start at age 28 rather than 32."