Effect of neonatal exposure to endosulfan on myometrial adaptation during early pregnancy and labor in rats

PACINI G; VARAYOUD J; ALARCÓN R; CADAVIZ DB; MILESI MM; LORENZ V; LUQUE EH

Congreso; Congress of International Federation of Placenta Associations 2019 (IFPA2019) and 8th Latin American Symposium on Maternal-Fetal Interaction and Placenta (VIII SLIMP),; 2019

Objectives: Proper myometrial adaptation during gestation is crucial forembryo implantation, pregnancy maintenance and parturition. Abnormalmyometrial differentiation or contractility might promote several reproductive disorders such as infertility, implantation failure or preterm birth.Previously, we reported that neonatal exposure to endosulfan altersuterine development and induces implantation failures. The present workinvestigates the effects of endosulfan exposure on myometrial differentiation at the pre-implantation period, and myometrial activation duringlabor.Methods: Newborn female rats were s.c. injected with corn oil (vehicle)or 600 mg/kg/day of endosulfan (Endo600) on postnatal days (PND) 1, 3, 5and 7. On PND90, the rats were mated to evaluate: i) the myometrialdifferentiation on gestational day 5 (GD5, pre-implantation period), byassessment myometrial histomorphology, smooth muscle cells proliferation, and expression of proteins involved in myometrial adaptation forembryo implantation (steroid receptors, Wnt7a and Hoxa10); ii) thetiming of parturition and myometrial activation during labor by determining the uterine expression of contraction-associated genes (oxytocinreceptor, OTXR; prostaglandin F2a receptor, PTGFR and connexin-43,Cx-43).Results: Endosulfan decreased the thickness of both myometrial layers,with a concomitant decrease in the collagen remodeling. Blood vesselsrelative area in the interstitial connective tissue between muscle layerswas also decreased. Endo600 group showed lower myometrial proliferation in association with a downregulation of Wnt7a and Hoxa10. Eventhough labor occurred on GD23 in both experimental groups, endosulfanaltered the timing of parturition by inducing advancement in the initiationof labor. This alteration was associated with an increased uterine expression of OTXR, PTGFR and Cx-43.Conclusion: In conclusion, neonatal exposure to endosulfan producedlong-term effects affecting myometrial adaptation during early pregnancy and labor. These alterations could be associated with the aberrant effects of endosulfan on the implantation process and the timingof parturition.