Leydig cell development in pubertal male rats is blocked by perfluorotetradecanoic acid through decreasing AMPK-mTOR-autophagy pathway

doi:10.1016/j.toxlet.2023.05.012

科研成果详情

题名	Leydig cell development in pubertal male rats is blocked by perfluorotetradecanoic acid through decreasing AMPK-mTOR-autophagy pathway
作者	Tang, Yunbing1; Shi, Lei1; Wang, Shaowei1; Lu, Han1; Li, Huitao2,3,4; Lv, Jieqiang1; Ge, Ren-shan1; Ying, Yingfen1
发表日期	2023-07-01
发表期刊	Toxicology letters 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	PFTeDA autophagy ferroptosis steroidogenesis testosterone
其他关键词	ACTIVATED PROTEIN-KINASE ; PERFLUOROALKYL SUBSTANCES ; MITOCHONDRIAL BIOGENESIS ; OXIDATIVE STRESS ; SERUM ; ASSOCIATION ; EXPOSURE ; GROWTH ; PERFLUOROOCTANOATE ; CARDIOMYOCYTES
摘要	Perfluorotetradecanoic acid (PFTeDA) is a type of perfluoroalkyl acid that has been linked to various health effects in animals and humans. The study aimed to investigate the potential impact of PFTeDA exposure on Leydig cell development in rats during puberty. Understanding the effects of PFTeDA on Leydig cells is crucial as these cells play a significant role in male reproductive function. Male Sprague-Dawley rats were gavaged with PFTeDA at doses of 0, 1, 5, and 10mg/kg/day from postnatal day 35 to 56. The serum hormone levels were measured and testicular transcriptome changes were analyzed by RNA-seq and verified by qPCR, and the levels of steroidogenesis-related proteins and energy regulators were measured. PFTeDA significantly reduced serum testosterone levels while slightly increasing LH levels. RNA-seq and qPCR analysis showed that genes responsive to oxidative phosphorylation (Naufa1 and Ndufs6) and steroidogenesis (Ldlr, Star, Cyp11a1) were markedly downregulated at ≥5mg/kg, while those related to ferroptosis (Alox15) and cell senescence (Map2k3 and RT1-CE3) were significantly upregulated. PFTeDA markedly reduced SIRT1 (silent information regulator 1) /PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α) and AMPKA (AMP activated kinase A), LC3B and Beclin1 (biomarkers for autophagy) levels while increasing phosphorylated mTOR. In vitro treatment of PFTeDA at 5 μM significantly reduced androgen output of Leydig cells from 35-day-old male rats while ferrostatin 1 (10 μM) reversed PFTeDA-mediated inhibition. In conclusion, the inhibitory effects of PFTeDA on pubertal rat Leydig cell development are possibly regulated by inducing ferroptosis thereby downregulating SIRT1/AMPKA/ autophagy pathways, eventually resulting in reduced steroidogenesis.
资助项目	Natural Science Foundation of China[81730042];Wenzhou Bureau of Science and Technology[Y20220387];
出版者	ELSEVIER IRELAND LTD
ISSN	0378-4274
EISSN	1879-3169
卷号	383 页码:43-53
DOI	10.1016/j.toxlet.2023.05.012
页数	11
WOS类目	Toxicology
WOS研究方向	Toxicology
WOS记录号	WOS:001022256000001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2023-06
URL	查看原文
PubMed ID	37269911
SCOPUSEID	2-s2.0-85161709235
通讯作者地址	[Ge, Ren-shan]The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325027,China
Scopus学科分类	Toxicology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/180639
专题	第二临床医学院、附属第二医院、育英儿童医院附属第二医院_麻醉重点学科实验室
通讯作者	Ge, Ren-shan
作者单位	1.Department of Obstetrics and Gynecology,the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 2.Key Laboratory of Anesthesiology of Zhejiang Province,Wenzhou Medical University,China; 3.Key Laboratory of Pediatric Anesthesiology,Ministry of Education,Wenzhou Medical University,China; 4.Department of Anesthesiology and Perioperative Medicine,The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou Medical University,China
第一作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院; 妇产科
通讯作者单位	第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
第一作者的第一单位	第二临床医学院，附属第二医院、育英儿童医院
推荐引用方式 GB/T 7714	Tang, Yunbing,Shi, Lei,Wang, Shaowei,et al. Leydig cell development in pubertal male rats is blocked by perfluorotetradecanoic acid through decreasing AMPK-mTOR-autophagy pathway[J]. Toxicology letters,2023,383:43-53.
APA	Tang, Yunbing., Shi, Lei., Wang, Shaowei., Lu, Han., Li, Huitao., ... & Ying, Yingfen. (2023). Leydig cell development in pubertal male rats is blocked by perfluorotetradecanoic acid through decreasing AMPK-mTOR-autophagy pathway. Toxicology letters, 383, 43-53.
MLA	Tang, Yunbing,et al."Leydig cell development in pubertal male rats is blocked by perfluorotetradecanoic acid through decreasing AMPK-mTOR-autophagy pathway".Toxicology letters 383(2023):43-53.