Functional and molecular characterisation of the uterus and cervix in a mouse model of reproductive ageing

Student thesis: Doctoral ThesisDoctor of Philosophy


Background: Advanced maternal age (≥35 years at delivery) is associated with increased rates of operative delivery, stillbirth, and post-term labour induction (Bewley et al., 2009). The physiological causes for such complications remain to be ascertained, although myometrial function has been implicated (Smith et al., 2008, Arrowsmith et al., 2012). To investigate the hypothesis that maternal age directly influences successful parturition, timing of birth and fetal outcome were assessed in a pregnant mouse model at three months (young) vs. eight months (older) of age using infra-red video recording. The impact of maternal age on the function of myometrium and cervix were also examined ex vivo using qPCR, isometric tension, immunohistochemistry, and measurement of the enzymatic activities of the mitochondrial electron transport chain complexes. Results: Older pregnant mice compared to three month old mice had significantly longer mean gestation and labour durations (p<0.001), as well as reduced litter size (p<0.01). Cervical tissues from older mice demonstrated greater distension compared to younger mice (p<0.05). However, collagen content and matrix metalloproteinase-2 protein expression were similar in late pregnant cervical tissues from three, five and eight month old mice. Expression of oxytocin receptor and connexin-43 mRNA were significantly reduced in myometrium from eight month vs. three month old mice (p<0.05, p<0.01 respectively). Spontaneous myometrial contractions were more frequent but of shorter duration in older pregnant mice (p<0.05); tissues from these older mice also exhibited reduced contractile response to oxytocin. Mitochondrial copy number was reduced in myometrium from eight month old mice, but there were no age-induced changes to the enzymatic activities of the mitochondrial electron transport chain complexes. Conclusions: In this mouse model of reproductive ageing, gestation and labour duration were prolonged. This is unlikely to be associated with delayed cervical softening. However, the alterations in spontaneous and oxytocin augmented contractions, coupled with a reduction in myometrial mitochondrial copy number in older mice, could potentially result in poorly coordinated myometrial contractions in-vivo. This study provided an insight into the reproductive ageing of myometrium in mice.
Date of Award2014
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorLucilla Poston (Supervisor) & Rachel Tribe (Supervisor)

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