When Gene Messages Go Wrong: Hidden Drivers of Endometriosis

Sometimes what happens later in life connects to the beginning of life, as it does for women’s reproductive health.

Hari Krishna Yalamanchili, PhD, principal investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and USDA-ARS Children’s Nutrition Research Center (CNRC) at Baylor College of Medicine, and Ramakrishna Kommagani, PhD, of Baylor College of Medicine recently published a new manuscript entitled, “Misregulated Alternative Splicing in Endometriosis: A Role for Aberrant mRNA Variants in Endometriotic Cell Growth” in the Nature journal, Cell Death and Discovery. The study probes the biological mechanisms behind endometriosis, a chronic gynecological disorder that remains poorly understood. Although endometriosis affects about 1 in 10 women worldwide, it’s still often diagnosed years too late, and treatment options beyond surgery remain limited. But the research described in this paper offers the possibility of developing novel diagnostic and therapeutic strategies that could help millions.

In this new study, Drs. Yalamanchili and Kommagani and their colleagues examined a lesser-explored layer of gene regulation called alternative splicing. Genes carry the instructions for making proteins, but those instructions are edited before they are used, similar to rearranging sections of a draft. The research team found that this cellular “editing” process goes off track in endometriotic tissue for two important genes, GALNT7 and ZNF28. As a result of the editing misfire, these genes may no longer function properly, allowing for abnormal cell growth.

Congratulations to Dr. Yalamanchili, Dr. Kommagani, and their coauthors for their important work on an often overlooked and sometimes debilitating condition. By mapping these gene changes, this work adds another piece to the puzzle of how endometriosis develops and points to new possibilities for future treatments that could reduce reliance on surgery and improve life for many women.