• PMID: 30513371
• Gene Name: SEPTIN12
• Condition: Severe spermatogenic defects
• Association: Associated
• Mutation: rs759992?T?>?C and rs3827527?C?>?T
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Severe spermatogenic defects

Identification of SEPTIN12 as a novel target of the androgen and estrogen receptors in human testicular cells

Kuo PL, Tseng JY, Chen HI, Wu CY, Omar HA, Wang CY, Cheng HY, Hsu CC, Fu TF, Teng YN.

SEPTIN12 (SEPT12) is a testis-enriched gene that is downregulated in the testis of infertile men with severe spermatogenic defects. While SEPT12 is involved in spermatogenic failure and sperm motility disorder, SEPT12 transcriptional regulation is still unknown. Here we report the promoter region of SEPT12 as a 245 bp segment upstream of the transcription start site. One androgen receptor (AR) and two estrogen receptor α (ERα) binding sites in this region were initially identified by bioinformatics prediction and confirmed by chromatin immunoprecipitation assay. Truncated ERα or AR binding sites decreased the promoter activity, which indicated that the ERα and AR are essential for the SEPT12 promoter. On the other hand, the promoter activity was enhanced by the treatment with 17β-estradiol (E2) and 5α-dihydrotestosterone (5α-DHT). Thus, one androgen and two estrogen hormone responsive elements located in the promoter of SEPT12 gene can regulate SEPT12 expression. Two single nucleotide polymorphisms (SNPs), rs759992 T > C and rs3827527 C > T, were observed in the SEPT12 gene promoter region and were able to decrease the promoter activity. In conclusion, the current work identified the promoter of the human SEPT12 gene and provided key evidence about its transcriptional regulation via E2 and 5α-DHT. Since SEPT12 has an important role in spermatogenesis, SEPT12 expression analysis can be developed as a potential tool for the assessment of environmental or food pollution by hormones or for the evaluation of the risk of endocrine-disrupting chemicals (EDCs) in general. CI - Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved. FAU - Kuo, Pao-Lin AU - Kuo PL AD - Department of Obstetrics & Gynecology, National Cheng Kung University, College of Medicine, Tainan, 701, Taiwan. FAU - Tseng, Jie-Yun AU - Tseng JY AD - Department of Biological Sciences and Technology, National University of Tainan, Tainan, 700, Taiwan. FAU - Chen, Hau-Inh AU - Chen HI AD - Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan. FAU - Wu, Chia-Yun AU - Wu CY AD - Department of Biological Sciences and Technology, National University of Tainan, Tainan, 700, Taiwan. FAU - Omar, Hany A AU - Omar HA AD - Sharjah Institute for Medical Research and College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates; Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, 62514, Egypt. FAU - Wang, Chia-Yih AU - Wang CY AD - Department of Cell Biology and Anatomy, National Cheng Kung University, College of Medicine, Tainan, 701, Taiwan; Institute of Basic Medical Sciences, National Cheng Kung University, College of Medicine, Tainan, 701, Taiwan. FAU - Cheng, Han-Yi AU - Cheng HY AD - Department of Biological Sciences and Technology, National University of Tainan, Tainan, 700, Taiwan. FAU - Hsu, Chao-Chin AU - Hsu CC AD - Institute of Reproductive Medicine, Taipei Medical University Hospital, Taipei, 110, Taiwan. FAU - Fu, Tzu-Fun AU - Fu TF AD - Institute of Basic Medical Sciences, National Cheng Kung University, College of Medicine, Tainan, 701, Taiwan.