319. RELAXIN REGULATES AQUAPORIN EXPRESSION IN THE CERVIX OF LATE PREGNANT MICE

Abstract

Aquaporins (AQPs) have been implicated in the regulation of fluid balance in the cervix during pregnancy to promote hydration, a characteristic of cervical ripening in late gestation. There are four AQPs in the cervix; AQP3, 4, 5 and 8. Cervical fluid balance involves AQP5 and 8 in early pregnancy and AQP3 and 4 in late pregnancy [1]. However, the factors involved in the regulation of cervical AQPs are unknown. We propose that the ovarian peptide hormone relaxin regulates cervical AQPs because high circulating levels of relaxin correspond to changes in AQPs and it is involved in cervical ripening. To test this hypothesis, expression of aqp3, 5 and 8 was compared in the cervices of relaxin wildtype (Rln+/+) and relaxin knockout (Rln–/–) at various stages of pregnancy (day 14.5, 16.5 and 18.5 pregnancy) by quantitative PCR. In the Rln–/– mice, aqp3 expression was significantly lower on day 18.5 gestation compared to Rln+/+ littermates. Aqp5 and 8 expression did not change significantly between genotypes. To determine whether relaxin could restore the Rln+/+ phenotype, Rln–/– mice were implanted with Alzet osmotic minipumps on day 12.5 pregnancy to infuse either recombinant H2 human relaxin (200 μg/mL; Corthera Inc) or 0.9% saline as a control. Cervices were collected after 4 or 6 days of infusion for gene expression analysis. Relaxin infusion in pregnant Rln–/– mice increased cervical aqp3, and also decreased aqp5 expression compared with saline-controls in the 6-day infusion group. Additionally, relaxin treatment caused a 6-fold increase in cervix wet weight, dispersal of collagen fibres and a decrease in relaxin receptor (Rxfp1) expression. These data suggest that relaxin promotes cervical hydration through an action on AQPs.

(1) Anderson et al, 2006. Endocrinology 147(1): 130–140.