Proceedings of The Physiological Society

Physiology 2016 (Dublin, Ireland) (2016) Proc Physiol Soc 37, PCB332

Poster Communications

The impact of maternal age on the initiation and progress of parturition in a pregnant murine model

R. Patel1, P. Poston1, R. M. Tribe1

1. Women's Health Academic Centre, King's College London, London, United Kingdom.

Background: Advanced maternal age (≥35 years at delivery) is associated with adverse obstetric risks including operative delivery, stillbirth, and post-term labour induction. The physiological causes for such complications remain to be fully ascertained, although myometrial function has been implicated (Smith GC et al., 2008; Arrowsmith et al., 2012, Elmes M et al., 2015). We have previously reported that ex vivo myometrium from older pregnant mice exhibits more frequent contractions (without an increase in mean integral tension), but had longer pregnancy gestations compared to younger mice. As an extension to this work, we have addressed the hypothesis that maternal age directly influences parturition as a result of altered circulating progesterone concentrations. Methods: Gestation length (days) and parturition duration (hours) in young (3 months old, n=8) and older (8 months old, n=8) nulliparous pregnant C57/BL6 mice were monitored using infrared cameras. The number of viable pups delivered per mouse was recorded. Serum progesterone was measured by ELISA from terminal blood samples taken throughout the end of gestation in nulliparous pregnant mice (days 15- 18/19; 3 months and 8 months, n=5-8 per group). Results: Older pregnant mice compared to 3 month old mice had a longer mean (±SEM) gestation (20.08 ±0.49 days vs. 19.05 ±0.25; p<0.001, Student's t-test) and significantly longer labours (3.68 ±0.83 hours vs. 1.01 ±0.41; p<0.001, Student's t-test). The 3 month old mice gave birth to a greater number of viable pups compared to older mice (7.5 ±0.53 vs. 4.8 ±2.2, p<0.01, Student's t-test); 50% of older mice had at least one stillborn pup. Younger 3 month old mice had a significant reduction in serum progesterone concentration from day 15 of gestation to day 18 (109.5 ±22.55 ng/ml vs. 30.5 ±6.59; p<0.01, ANOVA); however serum progesterone concentrations were similar throughout gestation for older mice (58.40 ±11.57- 80.88 ±12.13 ng/ml). Conclusions: Gestation length, labour duration and stillbirth risk were increased in older pregnant mice suggesting that there is an intrinsic problem with parturition processes in older mice. Progesterone withdrawal was apparent in younger mice, but not in older mice which could explain the longer gestations seen in these mice. The increased contraction frequency seen in this model of reproductive ageing ex vivo could indicate there are ineffective myometrial contractions in vivo, underpinning longer labour durations and increased risk of stillbirth.

Where applicable, experiments conform with Society ethical requirements