Journal Article

Prenatal two-hit stress affects maternal and offspring pregnancy outcomes and uterine gene expression in rats: match or mismatch?

Mccreary, J. Keiko, Weyers, Steven, Metz, Gerlinde A.S., Verstraeten, Barbara S.E., Olson, David M.

2019

Overview

Maternal stress and inflammation excesses can lead to adverse pregnancy outcomes and offspring development. We evaluated whether distinct prenatal stressors affect pregnancy, maternal and offspring outcomes, and uterine gene expression differently when combined than either alone. Long-Evans dams were exposed to psychological or/and (two-hit) immune stress (interleukin-1 beta [IL-1β]), on gestational days 12–18 and 17-delivery, respectively. Gestational length, maternal weight gain, glycaemia and corticosterone levels, offspring weight, and gender effects were recorded. Maternal and offspring uteri were collected at weaning and on postnatal day 160 correspondingly. Uterine expression of genes involved in local progesterone metabolism, neuroendocrine and immune systems were analyzed using quantitative real-time polymerase chain reaction. Maternal two-hit stress increased gestational length variation and the occurrence of adverse pregnancy outcomes while reducing gestational weight gain. Pup weight was negatively affected by prenatal stressors in a gender-specific way. In dams, IL-1β upregulated gene expression of neuroendocrine (Crh, Crhr1) and cytokine genes (Il1b, Il1rn, Il6, and Il10). Conversely, transcriptional patterns in offspring uteri were more variable with gene-specific up- or downregulation by each stressor separately, while exposure to both extensively reduced the expression of neuroendocrine (Hsd11b1), cytokine (Il1a, Il1rn, Il6), and IL-1 receptor genes. In conclusion, maternal stress affects physiological and molecular processes in dams and their offspring; two hits have different effects than single stressors. Outcomes appear generation-, gender-, and stressor-specific. Dampening of offspring uterine gene expression after exposure to multiple stressors could fit within the match/mismatch hypothesis of perinatal programming, with offspring preparing for a stressful life. Summary Sentence The combination of two distinct prenatal stressors, psychological and immune stress, induces adverse outcomes and differentially affects expression of genes related to progesterone metabolism, stress and the immune system in the rat uterus.

• Publisher: Society for the Study of Reproduction,Oxford University Press
• Subject: Animals / Behavior, Animal - physiology / Corticosterone - metabolism / corticotropin-releasing hormone (CRH/CRH receptor) / Cytokines / developmental origins of health and disease / early development / Female / fetal development / Gender / Gene Expression / Male / parturition / Pregnancy / Pregnancy Outcome - genetics / Prenatal Exposure Delayed Effects - genetics / Prenatal Exposure Delayed Effects - metabolism / Prenatal Exposure Delayed Effects - psychology / progesterone / Rats / Rats, Long-Evans / Reproductive health / rodents / steroid hormones/steroid hormone receptors / stress / Stress, Psychological - genetics / Stress, Psychological - metabolism / transcriptional regulation / uterus / Uterus - metabolism