Collagen Studies in Late Pregnant Relaxin Null Mice1

Abstract

The relaxin knockout (rlx -/-) mouse was used to assess the effect, during pregnancy, of relaxin with regard to water, collagen content, growth, and morphology of the nipple (N), vagina (V), uterus, cervix (C), pubic symphysis (PS), and mammary gland (MG). The results presented here indicate that during pregnancy, relaxin increases the growth of the N, C, V, and PS. Large increases in water content in the PS (20%) occurred in pregnant (Day 18.5) wild-type (rlx +/+) mice but not in rlx -/- animals. This indicates that in the PS, relaxin might increase the concentration of a water-retaining extracellular matrix component (hyaluronate). In the pregnant rlx +/+ mouse, collagen content decreased significantly in the N and V but not in other tissues. There were no significant changes in the rlx -/- mouse. This contrasts with findings in the rat, in which relaxin has been found to cause decreases in collagen concentrations in the V, C, and PS. Histological analysis showed that the collagen stain was more condensed in the tissues (V, C, PS, N, and MG) of rlx -/- mice than in those of rlx +/+ mice. This phenomenon indicates that the failure of collagen degradation and lack of growth in the N underlie the inability of the rlx -/- mice to feed their young, as reported previously. Vaginal and cervical luminal epithelia, which proliferated markedly in the rlx +/+ pregnant mice, remained relatively atrophic in the rlx -/- mice. As proliferation and differentiation of uterine and vaginal epithelia are thought to be induced by a paracrine stromal factor that acts upon estrogen stimulation, our results indicate that relaxin may be this paracrine factor.

Reduced expression of the PTH/PTHrP receptor during development of the mammary gland influences the function of the nipple during lactation

“…In the relaxin knockout mouse, milk is produced by the mammary gland but it accumulates in dilated ducts under the nipple and is not delivered to the pups (Zhao et al, 1999). The nipples of the relaxin knockout mouse fail to grow during pregnancy, and histological observations as well as protein extraction studies suggest that connective tissue was not remodeled during pregnancy (Zhao et al, 1999(Zhao et al, , 2000. Finally, the relaxin-null mouse did not exhibit a pregnancy-induced expansion in the size of smooth muscle bundles in the nipple (Zhao et al, 1999).…”

“…The release of matrix metalloproteinases (MMPs) is likely to underlie the remodeling of nipple connective tissue during pregnancy (Zhao et al, 2000). We chose to evaluate the expression of MMP13, MMP14, and MMP-2 (Bickeroff and Matrisian, 2002).…”

Relaxin Is a Key Mediator of Prostate Growth and Male Reproductive Tract Development

“…To identify the physiologic function of relaxin, the relaxin gene knockout mouse was established (Zhao et al, 1999(Zhao et al, , 2000, which has led to the confirmation of several relaxin-dependent phenotypes, established earlier in ovariectomized pregnant rats (Hwang et al, 1991;Kuenzi and Sherwood, 1992). Pregnant relaxindeficient mice showed impaired mammary gland and nipple development, as did relaxin-deficient (ovariectomized) pregnant rats.…”

Insights Into Parturition Biology From Genetically Altered Mice

“…Weight of pubic symphysis, vagina, and cervix in RLX Ϫ/Ϫ females does not increase by 1 d before term at the magnitude it does in RLX ϩ/ϩ females (59). In addition, pregnant RLX Ϫ/Ϫ females have denser collagen staining in vagina, pubic symphysis, and cervix than do RLX ϩ/ϩ females 1 d before term (59). Also, the pubic bones of RLX Ϫ/Ϫ females fail to widen to the extent that they do during the second half of pregnancy in wild-type gravid females (57).…”