Mechanisms of relaxin action in the reproductive tract: studies in the relaxin-deficient (Rlx-/-) mouse.

The major functions of relaxin (RLX) are associated with female reproductive tract physiology, namely, the regulation of biochemical processes involved in remodeling of extracellular matrix components in the cervix and vagina at term. Studies in RLX-deficient mice (Rlx-/-) demonstrate that although females give birth to live young without apparent dystocia, the pubic symphysis is not elongated, and they have abnormal cervical and vaginal morphology. The current study examined phenotypic differences in collagen, matrix metalloproteinases (MMP), and estrogen receptors (ERs) in the cervix and vagina of pregnant Rlx+/+ and Rlx-/- mice. Neither collagen nor TGFbeta1 mRNA levels in the cervix and vagina differed significantly between Rlx+/+ and Rlx-/- at any stage of gestation, except on gestation day 18.5, with an increase in alpha(1)-I collagen and TGFbeta1 expression in Rlx-/- mice. MMP gene expression was also increased in Rlx-/- mice, especially at term. Administration of recombinant H2 RLX (0.05 microg/microL/h) to Rlx-/- mice for 6 d from gestation day 12.5 caused a significant decrease in alpha1-I collagen and MMP-13 gene expression in the cervix and vagina, but it had no effect on TGFbeta1. There was also a significant reduction in ERbeta expression in RLX-treated Rlx-/- mice. Interestingly, RLX treatment caused a significant decrease in LGR7 expression in these reproductive tissues. In summary, these data show increases in MMP gene expression in Rlx-/- mice that are not correlated with changes in collagen expression. Furthermore, we report a novel ER phenotype in the cervix and vagina of Rlx-/- mice.