Morphological and molecular analysis of myometrial differentiation during early pregnancy in rats neonatally exposed to endosulfan.

RAMIRO ALARCÓN, ; ENRIQUE H. LUQUE,; MÓNICA M. MUÑOZ-DETORO, ; JORGELINA G. VARAYOUD, ; MA. MERCEDES MILESI

Mar del Plata, Argentina

Otro; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clinica.; 2016

&uring early pregnancy, the myometrium undergoes a notableincrease in proliferation, Yhich is critical for implantation. Alterationsof myometrial morphogenesis during development may leadto reproductive anomalies at adulthood. +n previous studies Yefound that neonatal exposure to the pesticide endosulfan altersthe expression of the morphoregulatory genes Hoxa and 9ntain the myometrium of prepubertal rats, and induces implantationfailures at adulthood. This study investigates the longterm effectsof neonatal exposure to endosulfan on myometrium differentiationduring the periimplantation period gestational day , )&. 0eYbornfemale rats Yere treated by s.c. injections every h frompostnatal day 20& to 20& Yith corn oil vehicle, diethylstilbestrol. zg/-g/day &ES, endocrine disruptor control and endosulfan zg/-g/day Endo. 1n 20&, females Yere matedand on )& the uteri Yere obtained, fixed and paraffinembedded.The thicMness of circular c/ and longitudinal l/ myometrium, asYell as, the relative area occupied by blood vessels Yere evaluatedin hematoxylineosin stained sections. 2rotein expression of -i as a cell proliferation marMer, 9nta, and Hoxa Yere evaluatedin the myometrium by immunohistochemistry. &ES treatmentincreased the thicMness of the c/ and the relative area occupiedby blood vessels, and enlarged intercellular spaces, suggesting thepresence of edema. Contrarily, Endo group shoYed a decreasein the thicMness of c/ and l/, in association Yith loYer cell proliferation.The treatment Yith endosulfan decreased the expressionof Hoxa in the l/, and doYnregulated 9nta in both myometriallayers. Endosulfaninduced Hoxa and 9nta deregulation in themyometrium might be responsible for the loYer proliferation rate,Yhich might be in turn the cause of loYer myometrial thicMness.These morphological and molecular changes could promote theendosulfaninduced implantation failures.