Conditional deletion of the relaxin receptor gene in cells of smooth muscle lineage affects lower reproductive tract in pregnant mice

Elena M. Kaftanovskaya, Zaohua Huang, Carolina Lopez, Kirk Conrad, Alexander I. Agoulnik

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Relaxin hormone secreted into the circulation during pregnancy was discovered through its effects on pubic symphysis relaxation and parturition. Genetic inactivation of the relaxin gene or its cognate relaxin family peptide receptor 1 (RXFP1) in mice caused failure of parturition and mammary nipple enlargement, as well as increased collagen fiber density in the cervix and vagina. However, the relaxin effect on discrete cells and tissues has yet to be determined. Using transgenic mice with a knockin LacZ reporter in the Rxfp1 allele, we showed strong expression of this gene in vaginal and cervical stromal cells, as well as pubic ligament cells. We produced a floxed Rxfp1 allele that was used in combination with the Tagln-cre transgene to generate mice with a smooth muscle-specific gene knockout. In pregnant females, the ROSA26 reporter activated by Tagln-cre was detected in smooth muscle cells of the cervix, vagina, uterine artery, and in cells of the pubic symphysis. In late pregnant females with conditional gene ablation, the length of pubic symphysis was significantly reduced compared with wildtype or heterozygous Rxfp1+/- females. Denser collagen content was revealed by Masson trichrome staining in reproductive tract organs, uterine artery, and pubic symphysis. The cervical and vaginal epithelium was less developed than in heterozygous or wild-type females, although nipple size was normal and the dams were able to nurse their pups. In summary, our data indicate that relaxin/RXFP1 signaling in smooth muscle cells is important for normal collagen turnover and relaxation of the pubic symphysis during pregnancy.

Original languageEnglish (US)
Article number91
JournalBiology of Reproduction
Volume92
Issue number4
DOIs
StatePublished - Apr 1 2015

Keywords

  • Conditional knockout
  • Female reproductive tract
  • Parturition
  • Pubic symphysis
  • Relaxin
  • RXFP1

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

Fingerprint

Dive into the research topics of 'Conditional deletion of the relaxin receptor gene in cells of smooth muscle lineage affects lower reproductive tract in pregnant mice'. Together they form a unique fingerprint.

Cite this