Altered Uterine Gene Expression in Lean and Obese Mice Following Maternal Oxytocin

Abstract

Background: Obese women exhibit higher rates of failed labor inductions with oxytocin. To investigate the mechanisms underlying parturition dysfunction in obese populations, we examined the changes in uterine gene expression profiles in lean and obese mice at term, with and without maternal oxytocin administration. Methods: Female C57BL/6 mice were fed either a high-fat or regular-lean diet for 6 weeks prior to conception and throughout pregnancy. At term, dams were given saline or oxytocin, with a second group of obese mice receiving high-dose oxytocin. Six hours later, uterine gene expression for 30 select transcripts associated with parturition (e.g. gap junctions, relaxation/contractility pathways, and oxytocin signaling) and obesity were analyzed by quantitative real time PCR. Results: Lean and obese uteri, at baseline, showed differential gene expression patterns at term. Oxytocin significantly altered the expression of numerous myometrial transcripts associated with parturition (gap junctions, relaxation/contractility pathways, and oxytocin signaling). The expression of numerous oxytocin-responsive genes depended on the dams’ body masses (lean vs. obese), with either blunted effects or no effects of oxytocin observed in obese mice vs. lean mice. Additionally, high-dose oxytocin did not consistently regulate parturition-related gene expression in obese uteri. In summary, gene expression patterns significantly differed in lean vs. obese uteri at term in the presence and absence of maternal oxytocin. Lean uteri were more responsive to oxytocin than obese uteri, even at higher doses of oxytocin. Conclusions: These findings support that blunted oxytocin responsiveness in obese uteri may contribute to obesity-related labor dysfunction.