The Effects of Chronic Exposure to EE2 in Early Life on Neurodevelop-ment and Spatial Learning Behavior in Adult Male Rats
17alpha-ethynylestradiol(EE2),a prevalent environmental endocrine disruptor primarily ingested orally,leads to its accumulation in the body.This study aimed to investigate the effects of neonatal exposure to EE2 on neurodevelopment and cognitive behavior in adulthood,as well as the underlying mechanism.Male Sprague-Daw-ley rats were exposed to low-dose EE2(0.1 μg·kg-1),high-dose EE2(10 µg·kg-1),or control for 16 weeks.The alterations in body weight and whole brain weight were determined,while neurobehavioral assessment was conduc-ted using Morris water maze and Open field test.Nissl staining and immunohistochemistry were employed to ob-serve morphology and expression of brain-derived neurotrophic factor(BDNF)in hippocampal regions CA1,CA3,and DG;Western Blot and biochemical assay measured levels of IL-1β,IL-10 protein,and malondialdehyde(MDA)in hippocampal/cortical tissues.The results showed that rats exposed to EE2 had lower weight growth and brain weight.Furthermore,the neurobehavioral performance indicated longer escape latency,reduced residence time in target quadrant and cross-platform times,also decreased movement distance in the central area,and less central residence time.These variations exhibited a dose-response relationship.Disorganized hippocampal neurons,irregu-lar cell shapes,and a decreased number of neuronal precursor cells were noticed in the DG area of the hippocam-pus compared with controls while elevated levels of IL-1β and decreased levels of IL-10 as well as increased MDA levels detected both cerebral cortex/hippocampus among rats exposed to EE2 along with decreased BDNF expres-sion in DG region for the low dose group and throughout entire region for high dose group.These findings imply that chronic exposure to EE2 at a dose of 0.1 µg·kg-1 during early-life in male rats can result in spatial learning deficits in adulthood,which might be associated with disorders in hippocampal formation,lower BDNF expression,and inflammation in both the cerebral cortex and hippocampus.
17α-ethynylestradiolratearly chronic exposurehippocampuslearning and memory behavior
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