Dissecting cervical goblet cell and mucus regulatory dynamics for the prevention of preterm birth

Goblet cells (GCs) secrete mucus that coats and protects our mucosal surfaces from vast quantities of microorganisms.

In the intestine and lungs, GC-intrinsic protection functions constantly; however, mucus structures in the female reproductive tract are dynamic, and primarily generated during pregnancy.

Cervical GCs appear early in gestation and secrete a cervical mucus plug (CMP) that blockades the cervical canal, preventing the passage of vaginal bacteria and maintaining uterine sterility.Ascending bacterial infections are linked to preterm birth, the leading single cause of global neonatal mortality.

CMP properties are altered in women at high risk of preterm delivery, suggesting a causal relationship to compromised CMP barrier function.

Despite their evident importance, very little is known regarding cervical GCs or the endogenous or exogenous factors responsible for the generation and maintenance of CMP protective functions.Our proposal will bridge this gap by applying state-of-the-art GC and mucus analytical tools to pre-clinical models to dissect the gestational GC develoment and identify regulators of CMP barrier function.

Furthermore, in depth molecular and functional characterisation of human CMP samples will be used to identify features associated with healthy and preterm delivery.

Addressing these objectives will deepen our understanding of gestational biology, and identify novel biomarkers or prophylactic strategies for diagnosing and preventing preterm birth.