Exposition to Enriched Environment Prevents Induced Preterm Labor in a Mice Model.

CORREA FERNANDO; ARIAS ANDREINA; JENSEN FEDERICO; BARIANI MARIA VICTORIA; SCHANDER JULIETA; WOLFSON MANUEL; FRANCHI ANA MARIA

WASHINGTON

Congreso; SSR 2017 Annual Meeting 50 Years of Research: Looking Back and Moving Forward; 2017

SOCIETY FOR THE STUDY OF REPRODUCTION

Preterm birth (PTB), defined as childbirth occurring before the week 37 of gestation, is a major determinant of neonatal mortality and morbidity. The precise biomolecular mechanisms, by which human parturition is spontaneously initiated, either at term or preterm, are not fully understood. Prenatal infection and consequent inflammation are the main causes of PTB and in turn, are key risk factors for the later development of cerebral palsy and neonatal sepsis. Our group developed a murine model of preterm labor, induced by injections of bacterial lipopolysaccharide (LPS) that produces an 85% of PTB. The effects of environmental enrichment (EE), which are mainly positive, are manifested by different molecular, cellular and physiological changes. And In general EE appears to be associated with an overall improvement in the psychological and physical wellbeing of animals. The aim of this work was to evaluate the effect of exposition to an EE as a potential treatment for reducing PTB rate in our mouse model. The EE protocol consisted in housing a group of ten six week old BALB/c females in larger cages containing a variety of objects, stairs, walkways, tunnels and wheels that provide optimal conditions for further exploration, visual, cognitive, social interaction and voluntary exercise activity. Standard conditions (control environment, CE) consisted of standard laboratory cages that housed 4 animals. After 6 weeks females were mated with males in regular cages and then pregnant females returned to EE (or CE) cages till day 15th of pregnancy, when LPS (or saline solution) was administered to evaluate percentage of PTB. So far we observed that pretreatment with EE felt by 35% LPS-induced PTB and offspring born from these mothers had a normal development. To evaluate possible mechanisms involved in this phenomenon we have studied different inflammatory mediators in uterus, and observed an impact of EE in the expression levels of CD14 and TLR-4 that were significantly diminished (p < 0 .05). Similarly, we observed that EE treatment significantly prevented the increase of NOS activity induced by LPS (p < 0 .05). Moreover, we analyzed leucocyte infiltration in cervix and uterus and observed that LPS increased leucocyte infiltration in both groups but we found epithelial infiltration only in CE treated mice. Results were analyzed by one-way ANOVA in a completely randomized design. Comparisons were made by Tukey?s test. Normality and homoscedasticity were tested by Shapiro?Wilk (modified) and Levene tests, respectively. In the case of data that did not meet the assumptions, normal scores transformation was applied and continued in the same way as with real data. Collectively, our results showed a protective effect of the enrichment of the environment against an immune challenge during pregnancy. This research was supported by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2010/0813; PICT 2013/0097) and Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 2012/0061).