PMID- 32437893 OWN - NLM STAT- MEDLINE DCOM- 20210219 LR - 20210219 IS - 1873-6351 (Electronic) IS - 0278-6915 (Linking) VI - 141 DP - 2020 Jul TI - Prenatal ethanol exposure-induced hypothalamic an imbalance of glutamatergic/GABAergic projections and low functional expression in male offspring rats. PG - 111419 LID - S0278-6915(20)30309-4 [pii] LID - 10.1016/j.fct.2020.111419 [doi] AB - This study was designed to demonstrate that prenatal ethanol exposure (PEE) can induce low functional expression of the hypothalamus in male offspring rats and explore the underlying mechanism. Pregnant rats were administered 4 g/kg ethanol or normal saline by oral gavage each day from gestational day (GD) 9 to GD20. Male GD20 foetuses and postnatal day 120 adult offspring rats were sacrificed under anaesthesia. Hypothalamic cells from male GD20~postnatal day (PD) 7 rats were treated with different doses of corticosterone and the glucocorticoid receptor (GR) antagonist mifepristone for 5 days. In this study, we found that PEE-induced overexposure of maternal glucocorticoids enhanced the expression of L-glutamic acid decarboxylase (GAD) 67 in the hypothalamic paraventricular nucleus (PVN) by activating the glucocorticoid metabolic activation system, further inducing the conversion of glutamate to L-gamma-aminobutyric acid (GABA) and developmental imbalance of glutamatergic/GABAergic projections to the PVN. The imbalance change was maintained until after birth, resulting in the inhibition of parvocellular neurons and low functional expression of the hypothalamus in PEE offspring rats. Our study indicated that low functional expression of the hypothalamus in male PEE offspring rats was associated with developmental programming of an imbalance of glutamatergic/GABAergic projections to the PVN. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Lu, Juan AU - Lu J AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China; Department of Orthopedics, Gansu Provincial Hospital of TCM Affiliated to Gansu University of Chinese Medicine, Gansu, 730050, China. FAU - Li, Qiang AU - Li Q AD - Department of Orthopedics, Gansu Provincial Hospital of TCM Affiliated to Gansu University of Chinese Medicine, Gansu, 730050, China. FAU - Ma, Guoqin AU - Ma G AD - Department of Orthopedics, Gansu Provincial Hospital of TCM Affiliated to Gansu University of Chinese Medicine, Gansu, 730050, China. FAU - Hong, Chenghao AU - Hong C AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China. FAU - Zhang, Wenqian AU - Zhang W AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China. FAU - Wang, Yuxia AU - Wang Y AD - Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China. Electronic address: sunneywang@126.com. FAU - Wang, Hui AU - Wang H AD - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China. Electronic address: wanghui19@whu.edu.cn. LA - eng PT - Journal Article DEP - 20200511 PL - England TA - Food Chem Toxicol JT - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JID - 8207483 RN - 3K9958V90M (Ethanol) RN - 3KX376GY7L (Glutamic Acid) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - 9002-60-2 (Adrenocorticotropic Hormone) RN - EC 4.1.1.15 (Glutamate Decarboxylase) RN - EC 4.1.1.15 (glutamate decarboxylase 1) RN - W980KJ009P (Corticosterone) SB - IM MH - Adrenocorticotropic Hormone/blood MH - Animals MH - Corticosterone/blood MH - Ethanol/*toxicity MH - Female MH - Fetal Weight MH - GABAergic Neurons/metabolism MH - Glutamate Decarboxylase/metabolism MH - Glutamic Acid/*metabolism MH - Male MH - Paraventricular Hypothalamic Nucleus/*drug effects/metabolism MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Rats MH - Rats, Wistar MH - gamma-Aminobutyric Acid/*metabolism OTO - NOTNLM OT - Developmental programming OT - Ethanol OT - Glucocorticoid metabolic activation system OT - Glutamatergic/GABAergic projections OT - Hypothalamus OT - Low functional expression COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/05/22 06:00 MHDA- 2021/02/20 06:00 CRDT- 2020/05/22 06:00 PHST- 2020/01/25 00:00 [received] PHST- 2020/05/05 00:00 [revised] PHST- 2020/05/05 00:00 [accepted] PHST- 2020/05/22 06:00 [pubmed] PHST- 2021/02/20 06:00 [medline] PHST- 2020/05/22 06:00 [entrez] AID - S0278-6915(20)30309-4 [pii] AID - 10.1016/j.fct.2020.111419 [doi] PST - ppublish SO - Food Chem Toxicol. 2020 Jul;141:111419. doi: 10.1016/j.fct.2020.111419. Epub 2020 May 11.