THE EFFECT OF SPERM-ASSOCIATED ANTIGEN-17 GENE (SPAG17) ON FUNCTION AND SIGNALING IN THE CERVIX

Advanced female age is associated with fibrosis in the reproductive tract, causing cervical dysfunction. As maternal age increases worldwide, there is a pressing need to prevent age-associated infertility and pregnancy complications. The molecular mechanisms underlying female reproductive aging and fibrosis are currently not well understood. We recently discovered a new mechanistic pathway implicated in aging and fibrosis via sperm associated antigen-17 (SPAG17) signaling. Our studies revealed SPAG17 localizes in the cervical stroma, and loss of function of this gene promotes increased collagen deposition, tightly packed extracellular matrix accumulation, and increased stiffness in the cervix of Spag17 knockout females compared to wild-type females, further complicating parturition. At the molecular level, Spag17 loss activates key aging-associated pathways, including proinflammatory, profibrotic, and senescence signaling. These results show SPAG17 is an important regulator of aging-related mechanisms in the cervix.