Maternal exposure to an enriched environment promotes uterine vascular remodeling and prevents embryo loss in mice

in Reproduction
Authors:
Fernanda L de la Cruz Borthiry Laboratorio de Fisiología y Farmacología de la Reproducción, Centro de Estudios Farmacológicos y Botánicos, UBA-CONICET, Ciudad Autónoma de Buenos Aires CP, Argentina
Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, UBA-CONICET, Ciudad Autónoma de Buenos Aires CP, Argentina

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Julieta A Schander Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, UBA-CONICET, Ciudad Autónoma de Buenos Aires CP, Argentina

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https://orcid.org/0000-0001-9079-4227
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Maximiliano Cella Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, UBA-CONICET, Ciudad Autónoma de Buenos Aires CP, Argentina

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Jimena S Beltrame Laboratorio de Fisiología y Farmacología de la Reproducción, Centro de Estudios Farmacológicos y Botánicos, UBA-CONICET, Ciudad Autónoma de Buenos Aires CP, Argentina

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Ana María Franchi Laboratorio de Fisiopatología de la Preñez y el Parto, Centro de Estudios Farmacológicos y Botánicos, UBA-CONICET, Ciudad Autónoma de Buenos Aires CP, Argentina

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María L Ribeiro Laboratorio de Fisiología y Farmacología de la Reproducción, Centro de Estudios Farmacológicos y Botánicos, UBA-CONICET, Ciudad Autónoma de Buenos Aires CP, Argentina

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Correspondence should be addressed to J S Beltrame; Email: jbeltrame@fmed.uba.ar
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Implantation-related events are crucial for pregnancy success. In particular, defects in vascular remodeling at the maternal–fetal interface are associated with spontaneous miscarriage and recurrent pregnancy loss. Physical activity and therapies oriented to reduce stress improve pregnancy outcomes. In animal models, environmental stimulation and enrichment are associated with enhanced well-being, cognitive function and stress resilience. Here, we studied whether the exposure of BALB/c mice to an enriched environment (EE) regulates crucial events during early gestation at the maternal–fetal interface. Pregnant BALB/c mice were exposed to the EE that combines non-invasive stimuli from the sensory pathway with voluntary physical activity. The pregnancy rate was evaluated. Implantation sites were investigated microscopically and macroscopically. Vascular adaptation parameters at the maternal–fetal interface were analyzed. We found that exposure to the EE prevented pregnancy loss between gestational days 7 and 15. Also, it increased the diameter of the uterine artery and decreased the wall:lumen ratio of the mesometrial decidual vessels, suggesting that EE exposure promotes vascular remodeling. Moreover, it increased nitric oxide synthase activity and inducible nitric oxide synthase expression, as well as prostaglandin F2a production and endoglin expression in the implantation sites. Exposure of pregnant females to the EE regulates uterine physiology, promoting vascular remodeling during early gestation. These adaptations might contribute to preventing embryo loss. Our results highlight the importance of the maternal environment for pregnancy success. The design of an ‘EE-like’ protocol for humans could be considered as a new non-pharmacologic strategy to prevent implantation failure and recurrent miscarriage.

 

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