The number of babies born preterm (before 37 weeks of gestation) is rising worldwide. Preterm birth is a major cause of postnatal abnormalities, adverse outcomes in later stages of life and additionally results in mortality. Chronic stress is known to be one of several causes of human preterm birth but there is no data on how stress affects premature births. Latest evidence from Gerlinde Metz of University of Lethbridge, Canada and colleagues addresses this important gap through an animal study published in BMC Medicine.
Metz and colleagues show for the first time in rats how maternal stress can influence preterm birth risk together with pregnancy and behavioral outcomes across three generations. The molecular mechanisms underlying the effects of stress were additionally investigated using microarray microRNA analyses and quantitative real time PCR studies using somatic samples, including brain, uterine and placental tissues.
Stress, simulated by restraint and forced swimming, was induced in pregnant rodents from gestational days 12-18, which is thought to be equivalent to the human second trimester. Their pregnant daughters, granddaughters and great-granddaughters’ were also stressed in a similar manner or served as non-stressed controls. Gestational length, maternal postpartum behaviour, maternal blood glucose, maternal plasma corticosterone levels, and offspring development were then analysed in each generation.
Stress reduced gestational length, maternal weight gain, and maternal behavioural activity, whilst it increased blood glucose levels up to the second generation of pregnant rats. Offspring growth was decreased and behaviour development delayed in the stressed animals across each cohort, with the largest effect seen in the third generation. MicroRNA expression changes were observed in the brains and uteri of granddaughters, and these alterations included the miR-200 family that regulates genetic pathways associated with brain plasticity and childbirth. Furthermore, stress was found to increase placental miR-181a, which is a marker of human preterm birth.
These original findings demonstrate that transgenerational prenatal stress is associated with preterm birth risk. Moreover, stress across generations also affects pregnancy outcomes, maternal behaviour and neonatal development. Interestingly, the stress induced epigenetic changes in placental tissue may have the potential to predict and prevent preterm birth and poor pregnancy outcomes in the clinic. Stress during the gestational period is therefore an important factor to consider for human health outcomes across, not just one, but several generations. Effective stress therapy and management programs will consequently be of use in reducing prenatal stress in the future, and alleviating its detrimental consequences over the generations.
Written by Ursula D’Souza, Senior Editor for BMC Medicine.