PMID- 32713334 OWN - NLM STAT- MEDLINE DCOM- 20211223 LR - 20211223 IS - 1875-5666 (Electronic) IS - 1566-5240 (Linking) VI - 21 IP - 3 DP - 2021 TI - The Melatonin and Enriched Environment Ameliorated Low Protein-Induced Intrauterine Growth Retardation by IGF-1 And mtor Signaling Pathway and Autophagy Inhibition in Rats. PG - 246-256 LID - 10.2174/1566524020666200726221735 [doi] AB - CDATA[Aim: The present study investigated whether melatonin (MEL) and enriched environment (EE) might protect against intrauterine growth retardation (IUGR) in rats. METHODS: Sprague-Dawley rats were randomly allocated to 3 groups: control (C), model (M) and EE+MEL group. Animals were housed in an enriched environment (EE+MEL group) or remained in a standard environment (C group, M group). IUGR rat model was built by feeding a low protein diet during pregnancy. MEL was administered by gavaging. At day 1 post-birth, the baseline characteristics and serum biochemical parameters, morphology of liver and small intestine, enzyme activities, and mRNA expression levels of fetal rats were determined. The autophagy marker LC3 and Beclin1 were determined by western blot analysis. RESULTS: EE+MEL markedly improved the baseline characteristics, hepatic and intestinal morphology of IUGR fetuses. In addition, the lactase activities in the fetal intestine were markedly increased by the EE+MEL. The levels of serum somatostatin (SST), Growth hormone (GH), GH releasing hormone (GHRH), Insulin-like Growth Factor 1 (IGF-1), triiodothyronine (T3), and tetraiodothyronine (T4) were found to be recovered by EE+MEL. In addition, the EE+MEL significantly ameliorated the mRNA expression of SST, GHRH, and GHRH receptor (GHRHR), GH, GHR, IGF-1, and IGF-1 receptor (IGF1R), IGF binding protein-1 (IGFBP1), mammalian target of rapamycin (mTOR), S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4EBP1) in fetuses. In IUGR fetal livers, LC3 and Beclin1 were found to be increased at birth, while LC3 and Beclin1 were observed to be significantly decreased in the EE+MEL group. CONCLUSION: EE+MEL could improve fetal rats' baseline characteristics, serum biochemical parameters, birth weight, intestinal and hepatic morphology and enzyme activities. These effects could be explained by the activation of the IGF-1/IGFBP1 and IGF-1/mTOR/S6K1/4EBP1 signaling pathway and autophagy inhibition. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Wang, Dan AU - Wang D AD - College of Human Kinesiology, Shenyang Sport University, 36 Jinqiansong East Road Sujiatun District, Shenyang, 110102, Liaoning, China. FAU - Wu, Xiao AU - Wu X AD - Department of basic medical, HE's University, Shenyang, Liaoning 110163, China. FAU - Lu, Dan AU - Lu D AD - College of clinical, HE's University, Shenyang, Liaoning 110163, China. FAU - Li, Yan AU - Li Y AD - Experimental Teaching Center of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang , Liaoning 110016, China. FAU - Zhang, Peng AU - Zhang P AD - Department of basic medical, HE's University, Shenyang, Liaoning 110163, China. LA - eng PT - Journal Article PL - Netherlands TA - Curr Mol Med JT - Current molecular medicine JID - 101093076 RN - 0 (Insulin-Like Growth Factor Binding Protein 1) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - 9002-72-6 (Growth Hormone) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - JL5DK93RCL (Melatonin) SB - IM MH - Animals MH - Autophagy/drug effects/genetics MH - Diet, Protein-Restricted/adverse effects MH - Disease Models, Animal MH - Female MH - Fetal Growth Retardation/*drug therapy/genetics/metabolism/pathology MH - Gene Expression Regulation/drug effects MH - Growth Hormone/genetics MH - Insulin-Like Growth Factor Binding Protein 1/genetics MH - Insulin-Like Growth Factor I/*genetics MH - Male MH - Melatonin/*pharmacology MH - Pregnancy MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction/drug effects MH - TOR Serine-Threonine Kinases/*genetics OTO - NOTNLM OT - Autophagy OT - Intrauterine growth restriction OT - Melatonin OT - enriched environment OT - insulin-like growth factor-1 OT - mTOR EDAT- 2020/07/28 06:00 MHDA- 2021/12/24 06:00 CRDT- 2020/07/28 06:00 PHST- 2020/03/10 00:00 [received] PHST- 2020/06/26 00:00 [revised] PHST- 2020/06/28 00:00 [accepted] PHST- 2020/07/28 06:00 [pubmed] PHST- 2021/12/24 06:00 [medline] PHST- 2020/07/28 06:00 [entrez] AID - CMM-EPUB-108465 [pii] AID - 10.2174/1566524020666200726221735 [doi] PST - ppublish SO - Curr Mol Med. 2021;21(3):246-256. doi: 10.2174/1566524020666200726221735.