Genistein up-regulates miR-20a to disrupt spermatogenesis via targeting Limk1
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Hao Gu1,2,3,*, Wei Wu1,2,4,*, Beilei Yuan1,2, Qiuqin Tang5, Dan Guo1,2, Yiqiu Chen1,2, Yankai Xia1,2, Lingqing Hu4, Daozhen Chen4, Jiahao Sha6 and Xinru Wang1,2
1State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China
2Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
3Department of Central Laboratory, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an 223002, China
4State Key Laboratory of Reproductive Medicine, Wuxi Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University, Wuxi 214002, China
5State Key Laboratory of Reproductive Medicine, Department of Obstetrics, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China
6State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China
*These authors contributed equally to the study and they should be regarded as joint first authors
Wei Wu, email: firstname.lastname@example.org
Qiuqin Tang, email: email@example.com
Keywords: genistein, miR-17-92 cluster, miR-20a, Limk1, spermatogenesis
Received: September 26, 2016 Accepted: April 16, 2017 Published: May 05, 2017
Genistein (GEN) is one of the isoflavones that has effect on male reproduction. However, the underlying mechanism remains unknown. miRNAs are a type of small non-coding RNAs that play important roles in spermatogenesis. We measured the GEN levels and miR-17-92 cluster expression in infertile subjects and found that miR-17-92 might be involved in GEN induced abnormal spermatogenesis. To clarify, we fed adult ICR mice with different doses of GEN (0, 0.5, 5, 50 and 250 mg/kg/day) for 35 days to study the underlying mechanism. We found that sperm average path velocity, straight-line velocity and eurvilinear velocity of the mice orally with GEN at 5mg/kg/day were significantly decreased, the expression levels of miR-17 and miR-20a in mice testis were higher in corresponding group. We also found miR-20a was the only miRNA that differentially expressed both in human and mice. By applying bioinformatics methods, Limk1 was predicted to be the target gene of miR-20a that is involved in spermatogenesis. Limk1 were significantly decreased in the corresponding group. Dual-luciferase report assay also proved that miR-20a could directly target Limk1. These results implied that Limk1 might be the target gene of miR-20a that is involved in GEN induced abnormal spermatogenesis.
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