The enrichment of maternal environment promotes vascular remodeling at the maternal-fetal interface during early gestation in mice.

DE LA CRUZ BORTHIRY, FL; BELTRAME JS; SCHANDER, JULIETA A.; CELLA, MAXIMILIANO; FRANCHI, AM; RIBEIRO, MARÍA LAURA

Modo virtual

Congreso; 2020 meeting of the Society for the study of reproduction SSR; 2020

The enrichment of maternal environment promotes vascular remodeling at thematernal-fetal interface during early gestation in mice. First trimester events associated to implantation are crucial for pregnancy success.Defects in these processes have been associated to the onset of many obstetricpathologies. In particularly, failure in vascular remodeling at the maternal-fetal interfaceaffects blood supply to the fetus and increases maternal blood pressure. Therefore, ithas been correlated with preeclampsia and intrauterine growth restriction.Maternal lifestyle affects the development of pregnancy. Therapies oriented to reducestress and physical activity have shown to improve pregnancy outcome. Furthermore,stress during gestation is associated with preeclampsia, which is linked to defectivevascular remodeling at the early placenta.We have previously demonstrated that female mice exposed preconceptionally andduring gestation to an enriched environment (EE) present higher reproductiveefficiency in day 15 of gestation, compared to females maintained in controlenvironment (CE) (80% vs 40%, p<0.05). Based on these antecedents, we hypothesized that the EE regulates crucial events atearly gestation that finally impact in the reproductive efficiency. Therefore, the aim ofthe present study was to investigate if EE exposure regulates vascular remodeling atthe maternal-fetal interface.Six-week-old female mice were housed in EE or CE cages for six weeks, and thenmated with CE fertile males. The EE strategy combines non-invasive stimulus of thesensory pathway with voluntary physical activity. Pregnant mice were sacrificed on day7 of pregnancy (d7). In one group of animals, the implantation sites were collected toperform PCR, western blot and histological studies. In the other group of females, theuterine arteries were clamped after sacrifice, and the uterine horns and the associatedvasculature were extracted to evaluate macrovasculature.Results: We found an increase in the uterine artery cross length in EE femalescompared to CE females (p<0.05). When we analyzed the microvasculature of theimplantation sites, no differences in the number or in the circumference of the vesselswere detected. However, the wall:lumen ratio was lower in EE females? vessels,suggesting that EE exposure promotes the vascular remodeling of the implantationsites. Moreover, we observed that NOS activity and iNOS expression were increased inthe implantation sites of EE housed females. Also, an increase in PGF 2α production andin the expression of endoglin and VEGFR-1 was detected in EE group compared tocontrol. No differences in the histological structure of the implantation sites wereobserved among the groups. Our results demonstrate that preconceptional and conceptional maternal exposure toEE promotes the remodeling of the vessels at the maternal-fetal interfase during earlygestation in mice (d7). We propose that the improvement in vascular remodeling mightbe the cause of the increment in the reproductive efficiency observed in d15 ofpregnancy. Therefore, the enrichment of the maternal environment might protect theprogression of pregnancy and help to alleviate obstetric complications.