Altered gestational parameters and offspring health in a rat model of subclinical infection. Beltrame

BELTRAME JS; SCHEFFER, FRIDA; CAÑUMIL, VA; DE LA CRUZ BORTHIRY, FL; BOGETTI E; FRANCHI, AM; RIBEIRO, ML

Rotorua

Congreso; 2023 Annual Meeting of the International Federation of Placenta Associations, Nueva Zelanda.; 2023

Altered gestational parameters and offspring health in a rat model of subclinical infection.Beltrame JS*, Scheffer F*, Cañumil VA, De la Cruz Borthiry FL, Bogetti E, Franchi AM, Ribeiro ML. Center of Pharmacology and Botanical Studies, UBA-CONICET, Argentina. *Both authors contributed equally. jbeltrame@fmed.uba.arSubclinical infections may 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 the offspring. In this context, our work aimed to evaluate whether subclinical infections affect gestation and its offspring in a rat model. Wistar female rats on days 6 to 9 of gestation received an intraperitoneal injection of lipopolysaccharide (LPS; 20 ug/kg on day 6 and 50 ug/kg on days 7-9) or vehicle. E. Coli LPS was used as a pro-inflammatory stimulus. Animals were euthanized on day 10 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 visible signs of inflammation. No leukocyte infiltration was observed in the kidney or liver. However, LPS-injected rats exhibited modified vascular development on days 10 and 15 of gestation. In addition, treatment with LPS decreases fetus weight on day 15. qPCR determinations (IL-6, TNFɑ, CXCL-10) on day 15 placentas showed altered expression of IL-6 after the LPS treatment. On the other hand, LPS  did not modify litter size or offspring weight on postnatal days 1 and 4. Nevertheless, LPS alters pup´s surface righting and the acquisition of mature posture parameters. Interestingly, male offspring from LPS-treated mothers presented a lower weight gain after weaning. Our results show that administered doses of LPS do not produce visible signs of infection in LPS-treated mothers. However, it affects the vascular adaptations of the uterus, intrauterine fetus growth, neurodevelopment, and weight gain of the pups. Altogether our results support the hypothesis that subclinical infections affect ongoing pregnancy and offspring.This work was supported by PICT 2019 N°00536.