Michaela M Morhaus, Lauren W Yowelunh McLester-Davis, Judith A Simcox
Advocated renaming Polycystic ovarian syndrome (PCOS) to Polyendocrine metabolic ovarian syndrome (PMOS) to reflect its systemic nature. Identified SF3B1 and IGFBP2 as molecular drivers of PMOS using a systems genetic approach combining murine and human data. SF3B1 inhibitors improved PMOS symptoms in mice, including decreased adiposity, hypoandrogenism, and insulin levels.
Polyendocrine metabolic ovarian syndrome (PMOS) affects one of every eight women worldwide and is associated with high rates of cardiovascular disease, type 2 diabetes, and infertility. Polycystic ovarian syndrome (PCOS), another term for this condition, reflects a historical focus on its effects on the female reproductive system. Recently, however, experts and patient groups have advocated renaming the condition PMOS, conveying increasing recognition that hyperandrogenism and insulin resistance contribute to its pathology. In this issue, Nguyen et al. took a systems genetic approach that combined data from murine models of PMOS and data from human studies, identifying the splicing factor 3b subunit 1 (SF3B1) and IGFBP2, both previously associated with metabolic disease, as molecular drivers of PMOS. SF3B1 inhibitors improved PMOS symptoms in mice, including decreased adiposity, hypoandrogenism, and insulin levels. These findings open therapeutic and mechanistic avenues in the study of PMOS, including exploration of splice variants as regulators of disease progression.