Effect of reproductive ageing on pregnant mouse uterus and cervix

Rima Patel (1, 2) , James D. Moffatt (3) , Evangelia Mourmoura (4) , Luc Demaison (5) , Paul T. Seed (1, 2) , Lucilla Postson (1, 2) , Rachel M. Tribe (1, 2)

1 Division of Women's Health
2 St Thomas' Hospital
3 Division of Biomedical Sciences
4 LBFA - Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée
5 UNH - Unité de Nutrition Humaine

Advanced maternal age (>/=35 years) is associated with increased rates of operative delivery, stillbirth, and post-term labour induction. The physiological causes remain uncertain, although impaired myometrial function has been implicated. To investigate the hypothesis that maternal age directly influences successful parturition, we assessed the timing of birth and fetal outcome in pregnant C57BL/6J mice at 3 months (young), 5 (intermediate) months vs. 8 months (older) of age using infra-red video recording. Serum progesterone profiles, myometrium and cervix function, and mitochondrial electron transport chain complex enzymatic activities were also examined. Older pregnant mice had longer mean gestation and labour duration (P < 0.001), as well as reduced litter size (P < 0.01) vs. 3 month old mice. Older mice did not exhibit the same decline in serum progesterone concentrations as younger mice. Cervical tissues from older mice were more distensible than younger mice (P < 0.05). Oxytocin receptor and connexin-43 mRNA expression were reduced in myometrium from 8 month vs. 3 month old mice (P < 0.05, P < 0.01 respectively) in tandem with more frequent, but shorter duration spontaneous myometrial contractions (P < 0.05) and an attenuated contractile response to oxytocin. Myometrial mitochondrial copy number was reduced in older mice, but there were no age-induced changes to the enzymatic activities of the mitochondrial electron transport chain complexes. In conclusion, 8 month old mice provide a useful model of reproductive ageing. This study has identified potential causes of labour dysfunction amenable to investigation in older primigravid women

Mots clés: maternal age; parturition; myometrium; risk factor; motherhood; pregnancy; animal models; mice

Mots clés: effet de l'âge; facteur de risque; maternité; grossesse; modèle animal; souris

Domaines: Médecine humaine et pathologie; Physiologie [q-bio.TO]

Rima Patel, James D. Moffatt, Evangelia Mourmoura, Luc Demaison, Paul T. Seed, et al.. Effect of reproductive ageing on pregnant mouse uterus and cervix. The Journal of Physiology, 2017, 595 (6), pp.2065-2084. ⟨10.1113/jp273350⟩. ⟨hal-01508153⟩