Role of relaxin and estrogen in the control of eosinophilic invasion and collagen remodeling in rat cervical tissue at term

Ripening and dilation of the rat cervix at term involves a widespread reduction in the density and organization of collagen fibers following a polymorphonuclear eosinophilic invasion. These are hormonally regulated events; however, the correlation between hormonal milieu and these morphological changes is not well understood. To investigate the role of preparturient relaxin and estradiol-17 beta (E-2) in cervical collagen remodeling and eosinophilic infiltration, pregnant rats were either sham-ovariectomized (group C) or ovariectomized in the morning of Day 22. Ovariectomized rats were treated with E-2 (group OE), relaxin (group OR), E-2 plus relaxin (group OER), or hormone vehicles (group O). There were 4 or 5 animals per group. Cervices were taken from animals killed approximately 1 h before expected parturition. Five-micrometer serial sections of paraffin-embedded cervices were stained with either Sirius Red in alkaline solution to measure eosinophil infiltration or in Picrosirius to measure collagen birefringence. Ovariectomized rats treated with E-2 (group OE or OER) showed high levels of eosinophilic infiltration that did not differ from those in group C intact controls. However, the values of eosinophilic infiltration in ovariectomized rats treated with relaxin or hormone vehicles (groups OR and O) were low and far below (p < 0.01) those of groups OE and C. In ovariectomized rats treated with E-2 alone (group OE), the widespread reduction in collagen organization that occurred in group C controls was not observed. It was only in ovariectomized rats treated with relaxin or E-2 + relaxin (groups OR and OER) that the values of birefringence were low, and they were as low as in control group C. In conclusion, this study indicates that eosinophilic infiltration and collagen remodeling in the rat cervix at term are under the control of different hormones: E-2 stimulates eosinophilic invasion, and relaxin promotes a widespread reorganization of collagen fibers.