Chronic mild maternal stress modulates the immune response at the maternal-fetal interface and affects the growth and mortality of the offspring

Abstract

Maternal lifestyle influences the health of both the mother and fetus. Acute stress is detrimental to health and increases the risk of obstetric complications. However, the consequences of chronic mild stress are less understood. We investigated the effect of chronic mild maternal stress on gestation and its influence on the immune response at the maternal-fetal interface. BALB/c female mice were exposed to a model of mild stress involving reduced litter material compared with the control condition. Also, a shaking protocol of 1 min every other day was initiated two weeks before mating and continued until euthanasia (days 7 or 15 of pregnancy) or term labor. The stressor stimulus increased the level of serum corticosterone. Furthermore, higher concentrations of total cholesterol and triglycerides were detected in the serum of stressed pregnant mice. Stressed mothers presented lower weight gain. The offspring born to stressed mothers showed lower weight on postnatal day one, and higher early neonatal mortality. No changes were observed in the number of implantation sites, the resorption rate, ovarian architecture, and histology. However, fetuses from stressed mice exhibited lower weights. Moreover, IL-6, IL-17, and TGF-β levels increased in the amniotic fluid of stressed mothers, while no changes were detected systemically. In addition, the protein expression of TLR-4 was increased in the uterus. Moreover, cyclooxygenase-2 and prostaglandin E₂ were decreased in the placenta. In conclusion, chronic mild maternal stress induces immunological alterations at the maternal-fetal interface affecting the health of the mothers during gestation and the development of the offspring.

Keywords: Chronic mild maternal stress; Inflammatory mediators; Maternal and offspring health; Maternal-fetal interface.