Lipopolysaccharide-induced subclinical infection affects pregnancy and impairs offspring development in an early gestation rat model

Abstract

Subclinical infections cause an imbalance of immune homeostasis that could have severe consequences for pregnancy and progeny development. We investigated if lipopolysaccharide (LPS)-induced subclinical infection affects vascular adaptations during gestation and offspring health. Wistar female rats received intraperitoneal vehicle (saline, control) or low doses of LPS from Escherichia coli (20 μg/kg on day 6 + 50 μg/kg on days 7-9 of gestation). Several parameters were evaluated on day 10 or 15 of pregnancy and the litter. No signs of infection or premature birth were registered after LPS treatment. Maternal survival was not affected by LPS administration. There were no differences in the number of implantation sites or fetuses between groups. However, the blood contained in the uterine and arcuate arteries, and the placentas from LPS-treated mothers exhibited a dark reddish-brown color. Moreover, LPS increased uterine and arcuate arteries' transversal length and decreased the number of vessels in the mesometrial decidua. These vessels showed a larger perimeter. Interestingly, LPS treatment decreased intrauterine fetus growth. No differences were observed in placental efficiency and placental zone areas. An imbalance in the levels of pro-inflammatory cytokines and vascular mediators was detected in the implantation sites and placenta. Furthermore, the offspring showed sex-specific impaired weight gain and neurodevelopment, although maturation milestones were not altered. Our findings show that LPS-induced subclinical infection affects pregnancy and offspring. These alterations are associated with deficiencies in key vascular processes and an imbalance in pro-inflammatory and vascular mediators at the maternal-fetal interface.

Keywords: Early gestation; Lipopolysaccharide; Offspring; Placenta; Vascular adaptations.