(380) Glycoprotein Olfactomedin 4 is Preferentially Expressed in Cervical Epithelia of Patients with Preterm Birth

Objective: Cervical epithelium is protected by a mucous layer that serves as an essential barrier against genitorurinary pathogens. Despite the central role of mucins in immune defense, we do not understand the regulatory pathways that drive mucus composition. We hypothesize that specialized secretory cells called goblet cells secrete the glycoprotein olfactomedin 4 (OLFM4) which plays an important role in mucosal defense during infection mediated preterm birth.

Study Design: Cervicovaginal fluid (CVF) samples (n=183) were obtained from patients in the first, second, and third trimester of pregnancy who had term (n = 20) or preterm (n = 30) birth. Of the patients with a preterm delivery, 14 had a genitourinary infection diagnosed during the pregnancy. OLFM4 expression in CVF samples was measured by enzyme-linked immunosorbent assays and normalized to the total protein concentration of each sample. Protein concentration between cohorts were compared using the Wilcoxon rank-sum test. Next, OLFM4 expression was analyzed in mouse cervical epithelium using RNA in situ hybridization. Finally, histologic studies were performed in OLFM4 deficient mice to characterize OLFM4 deficiency on cervical structure in pregnancy.

Results: Expression of OLFM4 is higher in preterm as compared to term CVF samples across all three trimesters, with the highest concentrations in the preterm patients who had a reproductive tract infection in pregnancy (p< 0.05) (Figure 1). In mice, OLFM4 is preferentially expressed in the pregnant state. Histologically, OLFM4 deficient mice had fewer goblet cells with secretory vacuoles and reduced mucin in the endocervical canal as compared to wild type controls (Figure 2).

Conclusion: In humans, while OLFM4 synthesis and secretion occurs throughout gestation, it is highest in patients with a preterm delivery and a reproductive tract infection. In mice, OLFM4 is preferentially expressed during pregnancy. The cervix of OLFM4 deficient mice has a distinct morphologic signature. Insights into such secretory proteins as OLFM4 can serve as biomarkers for infection-mediated preterm birth.