Effect of neonatal exposure to endosulfan on myometrial adaptation during early pregnancy and labor in rats. (1st July 2019)

• Record Type: Journal Article
• Authors: Alarcón, Ramiro; Varayoud, Jorgelina; Luque, Enrique H.; Milesi, María M.
• Is Part Of: Molecular and cellular endocrinology. Volume 491(2019)
• Publication Date: 2019-07-01
• Subjects: Endosulfan -- Myometrium -- Implantation -- Labor; Endo600 female rat group treated with 600 μg/kg/d of endosulfan -- PND postnatal day -- GD gestational day -- SMCs smooth muscle cells -- EDCs endocrine-disrupting compounds -- IOD integral optical density -- NOEL no observed effect level -- Vv Volume fraction -- ERα estrogen receptor α -- PR progesterone receptor -- OTXR oxytocin receptor -- PTGFR prostaglandin F2α receptor -- Cx-43 connexin 43 -- L19 ribosomal protein L19 -- Ct comparative cycle threshold; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2019.04.015
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Proper myometrial adaptation during gestation is crucial for embryo implantation, pregnancy maintenance and parturition. Previously, we reported that neonatal exposure to endosulfan alters uterine development and induces implantation failures. The present work investigates the effects of endosulfan exposure on myometrial differentiation at the pre-implantation period, and myometrial activation during labor. Newborn female rats were s.c. injected with corn oil (vehicle) or 600 μg/kg/day of endosulfan (Endo600) on postnatal days (PND) 1, 3, 5 and 7. On PND90, the rats were mated to evaluate: i) the myometrial differentiation on gestational day 5 (GD5, pre-implantation period), by assessment myometrial histomorphology, smooth muscle cells (SMCs) proliferation, and expression of proteins involved in myometrial adaptation for embryo implantation (steroid receptors, Wnt7a and Hoxa10); ii) the timing of parturition and myometrial activation during labor by determining the uterine expression of contraction-associated genes (oxytocin receptor, OTXR ; prostaglandin F2 α receptor, PTGFR and connexin-43, Cx-43 ). Endosulfan decreased the thickness of both myometrial layers, with a concomitant decrease in the collagen remodeling. Blood vessels relative area in the interstitial connective tissue between muscle layers was also decreased. Endo600 group showed lower myometrial proliferation in association with a downregulation of Wnt7a and Hoxa10. Although in all females labor occurred on GD23, the exposure to endosulfan altered the timing of parturition, by inducing advancement in the initiation of labor. This alteration was associated with an increased uterine expression of OTXR, PTGFR and Cx-43 . In conclusion, neonatal exposure to endosulfan produced long-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 timing of parturition. Highlights: Neonatal exposure to endosulfan induced morphological and molecular alterations in the myometrium at early pregnancy. Endosulfan altered myometrial adaptation during labor by increasing the expression of contraction-associated genes. Endosulfan altered the timing of parturition by inducing advancement in the initiation of labor.