Endocrine Abstracts

Introduction: Labour is an inflammatory process involving the innate immune system, premature activation of which, for example by infection, can lead to preterm birth before 37 weeks of gestation with profound pathophysiological consequences for the offspring. The putative antimicrobial protein HRPE773 (ZG16B) expressed in human female reproductive secretory epithelia, has been shown previously to be elevated in human endometrium during the menstrual early secretory phase and in uterine decidua following miscarriage. We therefore hypothesized that HRPE773 expression might be regulated by inflammatory stimuli in female reproductive tissues.

Methods: Human amnion, chorio-decidua, placenta, myometrium and cervix collected with informed consent from donors undergoing natural labour at 40+ weeks gestation or elective caesarean section between weeks 39 and 43 gestation, were obtained through the Edinburgh Reproductive Tissue Bio Bank. QRT-PCR using the 2−ΔΔCt method with 18SRNA as internal standard and immunohistochemistry were used respectively to determine HRPE773 mRNA levels and protein localization. HRPE773 expression was also measured in RNA from ectocervical (ECT1/E6E7) and endocervical (END1/E6E7) cell lines treated with IL1β or LPS inflammatory mediators for 24 h. Statistical analyses were performed using the Mann–Whitney U test or one-way ANOVA (CI 95%), with Tukey’s post hoc testing.

Results: HRPE773 expression was significantly higher in amnion from normal term labour compared to caesarean section (P<0.05), whilst no differences were observed in chorio-decidua, placenta or myometrium. HRPE773 expression was significantly up-regulated in ectocervical cells following treatment with IL1β or LPS (P<0.05). Finally, HRPE773 immunoreactivity was localised primarily in epithelia of foetal membranes and cervix, myometrial endothelium and fibrotic lesions in placenta.

Conclusions: HRPE773 is normally expressed at low levels in female reproductive tissues, but up-regulation in normal term amnion and ectocervical cell lines treated with inflammatory mediators suggests a possible role during labour. Epithelial localisation of HRPE773 protein in reproductive tissues is consistent with an innate immune function.