CONICET | Buscador de Institutos y Recursos Humanos

Lipopolysaccharide as a pro-inflammatory stimulus modulates the ongoing pregnancy and offspring in a rat model of subclinical infection.Scheffer F, Cañumil VA, De la Cruz Borthiry FL, Bogetti E, Franchi AM, Ribeiro ML, Beltrame JS*. Center of Pharmacology and Botanical Studies, UBA-CONICET, Argentina.The origin of early pregnancy loss is unknown in at least 50% of cases. One hypothesis holds that subclinical infections cause an imbalance in pro- vs. anti-inflammatory responses, with severe consequences for pregnancy progress. It has been postulated that alterations in the inflammatory response of the maternal-fetal interface could cause placental dysfunction, impacting the development of offspring. In this context, we postulate that vascular remodeling could be a target of pro-inflammatory situations since it is highly regulated by the trophoblast and by the decidual immune system. Wistar female rats on days 6, 7, 8, and 9 of gestation received an intraperitoneal injection of lipopolysaccharide (LPS; 20 μg/mg on day 6 and 50 μg/mg on days 7, 8, and 9) or vehicle. E. Coli LPS was used as a pro-inflammatory stimulus. Animals were euthanized on day 9 of gestation to study the ongoing vascular remodeling, on day 15 to study the placentas, or allowed to reach term. Several parameters were measured on fetuses, placentas, mothers, and pups. Differences between means were significant when p<0.05. The LPS-treated rats did not exhibit piloerection, increased body temperature, decreased feeding, or lack of movement, showing no macroscopic symptoms of inflammation. No leukocyte infiltration was observed in the kidney, lung, or liver. Besides, no differences were found in the number of live fetuses or embryo resorption on day 15 of gestation. However, LPS-injected rats exhibited modified uterine and arcuate artery vascular development on days 9 and 15 of gestation. In addition, treatment with LPS decreases fetus weight on day 15. On the other hand, the LPS treatment did not modify litter size, or offspring weight on postnatal days 1 and 4. However, LPS alters the turnover of the pups and the acquisition of a mature position. Our results show that administered doses of LPS do not produce visible symptoms of infection, however, it affects the vascular adaptations of the uterus, intrauterine fetus growth, and offspring neurodevelopment. Altogether our results support the hypothesis that subclinical infections affect ongoing pregnancy and offspring.This work was supported by PICT 2019 N°00536.

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