Older female mice were less likely to get pregnant, probably because of structural abnormalities of the uterus, and the oldest mice failed to get pregnant.
The team discovered that ANTXR2 regulates enzymes called matrix metalloproteinases (MMPs), which promote remodeling of the extracellular tissue—called extracellular matrix (ECM) —of the cervix. During pregnancy, the ECM helps to maintain cervical firmness and structure. At the end of the pregnancy, ANTXR2 promotes ECM remodeling so that the cervix softens and dilates, a process called ripening. “The mice that did get pregnant,” said Dr. Kitajewski, “were unable to deliver because their cervices failed to ripen and their uterine tissue had excessive ECM.”
If the cervix ripens prematurely, a condition called cervical insufficiency, the result is preterm labor and premature birth. “Based on the ANTXR2 mutant mice,” said postdoctoral fellow Claire Reeves, “we believe dysregulation of the MMPs by ANTXR2 could lead to cervical insufficiency.” These findings led to the formation of the Collaborative Cervical Research Group at Columbia and efforts to develop a test to determine the risk of preterm labor in humans.