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

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 wer...

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Bibliographic Details
Published in:Biology of reproduction 2019-01, Vol.100 (1), p.195-207
Main Authors: Verstraeten, Barbara S.E, Mccreary, J. Keiko, Weyers, Steven, Metz, Gerlinde A.S, Olson, David M
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:0006-3363
1529-7268
DOI:10.1093/biolre/ioy166