Obesity modifies the implantation window and disrupts intrauterine embryo positioning in rats

in Reproduction
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  • 1 Universidad de Buenos Aires (UBA), Facultad de Ciencias Exactas y Naturales (FCEN), Buenos Aires, Argentina
  • 2 Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)-UBA- Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires, Argentina
  • 3 UBA, FCEN, Departamento de Fisiología, Biología Molecular y Celular, Buenos Aires, Argentina
  • 4 UBA, FCEN, Departamento de Biodiversidad y Bilogía Experimental, Buenos Aires, Argentina
  • 5 UBA, FCEN, Instituto de Biociencias, Biotecnología y Biología Traslacional (IB3), Buenos Aires, Argentina

Correspondence should be addressed to E Elia; E-mail: evelinmariel@gmail.com
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Obesity is a chronic disease that impairs female reproduction. When gestation is achieved, maternal obesity can cause offspring’s health complications. We intended to evaluate the effects of maternal pre-conceptional obesity on uterine contractile activity, embryo implantation and offspring development. Using cafeteria diet-induced obesity as an animal model, we found that maternal obesity delays embryo transport from the oviduct to the uterus and alters the intrauterine embryo positioning. Adrenergic receptor (AR) signaling is involved in embryo positioning, so all AR isoforms were screened in the pre-implantation uteri. We found that the β2AR is the dominant isoform in the rat uteri and that obesity causes its upregulation. Although β2AR activation is known to induce uterine relaxation, higher spontaneous contractile activity was detected in obese dams. Uteri from obese dams showed a higher sensitivity to salbutamol (a selective agonist of β2AR) than controls, consistent with the higher β2AR levels detected in those animals. Despite this, in obese dams, some embryos were still in the oviduct at the predicted time of initial embryo attachment, embryo implantation is successfully carried out since the total number of fetuses on gd 18.5 were similar between control and obese dams. These findings show that obesity is modifying the implantation window. Moreover, we found that maternal obesity resulted in macrosomia in the offspring, which is an important predictor of fetal programming of postnatal health. Hence, our results show that maternal obesity prior to pregnancy not only disturbs the implantation process, but also affects offspring development.

 

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