During the later stages of pregnancy there is increased synthesis of cervical hyaluronan and it has been assumed that this is important for remodelling of the cervix to facilitate birth. Surprisingly, when Akgul et al. conditionally depleted hyaluronan from the female reproductive tract in mice, they found that this did not affect tissue compliance and matrix remodelling in the cervix during pregnancy and parturition. Instead, hyaluronan depletion compromised cervical epithelial cell differentiation and led to disruption of epithelial barrier function. This increased the susceptibility of mice to vaginal bacterial infections, with hyaluronan-depleted mice showing increased rates of preterm birth in response to vaginal innoculation with Escherichia coli. These findings may aid in the development of new therapies for preterm birth, which is responsible for 3.3 million perinatal deaths globally each year.