Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (4): 42-47.doi: 10.6040/j.issn.1671-7554.0.2021.0056

Previous Articles     Next Articles

Effect of testosterone on the expression of polycystic ovary syndrome susceptibility gene Tox3 in zebrafish

HAN Xiao, LI Lei, LIU Congcong   

  1. Center for Reproductive Medicine, Shandong University;
    Key Laboratory for Reproductive Endocrinology of Education Ministry;
    Shandong Provincial Key Laboratory of Reproductive Medicine;
    National Research Center for Assisted Reproduction and Reproductive Genetics, Jinan 250001, Shandong, China
  • Published:2021-04-30

Abstract: Objective To determine the expression of polycystic ovary syndrome(PCOS)susceptibility gene Tox3 in wild-type zebrafish, and explore the effect of testosterone on Tox3 gene expression. Methods About 200 zebrafish embryos and 100 male and female adult zebrafish for control treatment and testosterone(10 ng/mL)treatment were required. Reverse transcription-polymerase chain reaction(RT-PCR)and real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)were used to test the expression of Tox3 gene in zebrafish. The distributions of Tox3 mRNA in zebrafish embryos were observed by whole mount in situ hybridization(WISH). Results In wild-type zebrafish, the level of Tox3 gene expression was high in the nervous system and reproductive system. After treated with 10 ng/mL testosterone, compared with the control group, the Tox3 gene expression of male zebrafish treated with 10 ng/mL testosterone was higher in brain [(1.01±0.19) vs(1.43±0.35),P=0.043] and in nest [(1.05±0.32) vs(1.50±0.30),P=0.015]. Conclusion Tox3 in zebrafish may regulates the synthesis and release of androgen by acting on neuroendocrine systems.

Key words: Testosterone, Polycystic ovary syndrome, Tox3, Gene expression, Zebrafish

CLC Number: 

  • R711
[1] Abbott DH, Dumesic DA, Franks S. Developmental origin of polycystic ovary syndrome—a hypothesis[J]. J Endocrinol, 2002, 174(1): 1-5.
[2] Dumesic DA, Oberfield SE, Stener-Victorin E. Scientific statement on the diagnostic criteria, epidemiology, path-ophysiology, and molecular genetics of polycystic ovary syndrome[J]. Endocr Rev, 2015, 36(5): 487-525.
[3] Shi Y, Zhao H, Shi Y, et al. Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome[J]. Nat Genet, 2012, 44(9): 1020-1025.
[4] Cui Y, Zhao S, Zhao H, et al. Mutational analysis of Tox3 in Chinese Han women with polycystic ovary syndrome[J]. Reprod Biomed Online, 2014, 29(6): 752-755.
[5] Dittmer S, Kovacs Z, Yuan SH, et al. TOX3 is a neuronal survival factor that induces transcription depending on the presence of CITED1 or phosphorylated CREB in the transcriptionally active complex[J]. J Cell Sci, 2011, 124(Pt 2): 252-260.
[6] Ackermann GE, Paw BH. Zebrafish: a genetic model for vertebrate organogenesis and human disorders[J]. Front Biosci, 2003, 8: d1227-d1253. doi: 10.2741/1092.
[7] Kabashi E, Brustein E, Champagne N. Zebrafish models for the functional genomics of neurogenetic disorders[J]. Biochim Biophys Acta, 2011, 1812(3): 335-345.
[8] Diaz N, Piferrer F. Estrogen exposure overrides the masculinizing effect of elevated temperature by a downregulation of the key genes implicated in sexual differentiation in a fish with mixed genetic and environmental sex determination[J]. BMC Genomics, 2017, 18(1): 973. doi: 10.1186/s12864-017-4345-7.
[9] Walters KA, Gilchrist RB, Ledger WL. New perspectives on the pathogenesis of PCOS: neuroendocrine origins[J]. Trends Endocrinol Metab, 2018, 29(12): 841-852.
[10] Trimèche S, Thuan Dit Dieudonne JF, Jeandel C, et al. [Polycystic ovary syndrome in pubertal period: clinical, biological, metabolic and genetic polymorphism] [J]. Gynecol Obstet Fertil, 2004, 32(1): 3-17.
[11] Stacey SN, Manolescu A, Sulem P, et al. Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer[J]. Nat Genet, 2007, 39(7): 865-869.
[12] Jiang B, Chen W, Qin H, et al. TOX3 inhibits cancer cell migration and invasion via transcriptional regulation of SNAI1 and SNAI2 in clear cell renal cell carcinoma[J]. Cancer Lett, 2019, 449: 76-86. doi: 10.1016/j.canlet.2019.02.020.
[13] Gao J, Liu S, Zhang Y, et al. Effects of 17 α-methyltestosterone on transcriptome, gonadal histology and sex steroid hormones in rare minnow Gobiocypris rarus[J]. Comp Biochem Physiol Part D Genomics Proteomics, 2015, 15: 20-27. doi: 10.1016/j.cbd.2015.05.001.
[14] Gudmundsdottir ET, Barkardottir RB, Arason A, et al. The risk allele of SNP rs3803662 and the mRNA level of its closest genes TOX3 and LOC643714 predict adverse outcome for breast cancer patients[J]. BMC Cancer, 2012, 12: 621. doi: 10.1186/1471-2407-12-621.
[15] Fuh JL, Chung MY, Yao SC, et al. Susceptible genes of restless legs syndrome in migraine[J]. Cephalalgia, 2016, 36(11): 1028-1037.
[16] Jiang C, Yu S, Qian P, et al. The breast cancer susceptibility-related polymorphisms at the TOX3/LOC643714 locus associated with lung cancer risk in a Han Chinese population[J]. Oncotarget, 2016, 7(37): 59742-59753.
[17] OFlaherty E, Kaye J. TOX defines a conserved subfamily of HMG-box proteins[J]. BMC Genomics, 2003, 4(1): 13. doi: 10.1186/1471-2164-4-13.
[18] Yuan SH, Qiu Z, Ghosh A. TOX3 regulates calcium-dependent transcription in neurons[J]. Proc Natl Acad Sci U S A, 2009, 106(8): 2909-2914.
[19] Seksenyan A, Kadavallore A, Walts AE, et al. TOX3 is expressed in mammary ER(+)epithelial cells and regulates ER target genes in luminal breast cancer[J]. BMC Cancer, 2015, 15: 22. doi: 10.1186/s12885-015-1018-2.
[20] May JV, Schomberg DW. Granulosa cell differentiation in vitro: effect of insulin on growth and functional integrity[J]. Biol Reprod, 1981, 25(2): 421-431.
[21] Sahu SK, Fritz A, Tiwari N, et al. TOX3 regulates neural progenitor identity[J]. Biochim Biophys Acta, 2016, 1859(7): 833-840.
[22] Ning Z, Jiayi L, Jian R. Relationship between abnormal TOX3 gene methylation and polycystic ovarian syndrome[J]. Eur Rev Med Pharmacol Sci, 2017, 21(9): 2034-2038.
[23] Xu Y, Li Z, Ai F, et al. Systematic evaluation of genetic variants for polycystic ovary syndrome in a Chinese population[J]. PLoS One, 2015, 10(10): e0140695. doi: 10.1371/journal.pone.0140695.
[24] Zhang X, Zhu H, Wu X, et al. A genetic polymorphism in TOX3 is associated with survival of gastric cancer in a Chinese population[J]. PLoS One, 2013, 8(9): e72186. doi: 10.1371/journal.pone.0072186.
[25] Lee CH, Hur SW, Na OS, et al. Induction of Primary Male in Juvenile Red Spotted Grouper Epinephelus akaara by Immersion of 17α-Methyltestosterone[J]. Dev Reprod, 2014, 18(3):127-131.
[1] SONG Tian, FU Linlin, WANG Qiumin, YANG Xiao, WANG Ying, BIAN Yuehong, SHI Yuhua. Expression of fatty acid transport protein 1 in granulosa cells of patients with polycystic ovary syndrome [J]. Journal of Shandong University (Health Sciences), 2022, 60(2): 22-26.
[2] GONG Xiaoshu, WU Richao, LI Xiufang, PAN Ye, WANG Ze, SHI Yuhua. Effect of different ovulation induction regimens for endometrial preparation on the outcome of frozen-thawed embryo transfer among 603 women with polycystic ovary syndrome [J]. Journal of Shandong University (Health Sciences), 2021, 59(3): 48-54.
[3] HA Lingxia, YIN Ting, WU Yangyang, LI Weixia, DU Yudong. Correlation between insulin resistance and expressions of local inflammatory factors and glucose transporter protein type-4 in the endometrium of patients with polycystic ovary syndrome [J]. Journal of Shandong University (Health Sciences), 2021, 59(11): 41-47.
[4] DING Xiangyun, YU Qingmei, ZHANG Wenfang, ZHUANG Yuan, HAO Jing. Correlation of the expression of insulin-like growth factor II in granulosa cells and ovulation induction outcomes of 84 patients with polycystic ovary syndrome [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 60-66.
[5] SONG Haixia,YUAN Caixia,FAN Lingling. Impact of body mass index on pregnancy outcomes in artificial insemination by husband [J]. Journal of Shandong University (Health Sciences), 2020, 58(1): 49-53.
[6] HE Tingting, LIU Hong, SHU Kaiyun, SONG Xiaocui, SHI Yuhua. Expression and significance of microRNA-141 in granulosa cells of patients with polycystic ovary syndrome [J]. Journal of Shandong University (Health Sciences), 2019, 57(5): 116-120.
[7] HE Tingting, LIU Xin, LIU Hongbin, ZHAO Shigang, ZHANG Xiuqing, LIU Qingqing, YOU Li, SHI Yuhua. Expression of Forkhead box protein O1 mRNA in granulosa cells of polycystic ovary sydrome patients and its significance [J]. Journal of Shandong University (Health Sciences), 2019, 57(2): 75-79.
[8] LIU Congcong, LIU Hongbin, FU Jiang, LI Lei. Expression of polycystic ovary syndrome susceptibility gene dennd1a in zebrafish models [J]. Journal of Shandong University (Health Sciences), 2019, 57(1): 48-54.
[9] LIU Fasheng, HAN Jian, LI Sha, SHANG Hongyuan, MA Min, WANG Rongchun, ZHANG Aiping, HAN Liwen. Effect of nano titanium dioxide and copper ions on the developmental toxicity of zebrafish embryo [J]. Journal of Shandong University (Health Sciences), 2018, 56(7): 33-38.
[10] SHU Xin, WANG Qun, HUANG Tao, ZHAO Shigang, SHI Yuhua, LIU Hongbin. Expression of FBP1 in granulosa cells of PCOS patients with hyperandrogenism and its significance [J]. Journal of Shandong University (Health Sciences), 2018, 56(4): 58-63.
[11] ZHANG Suping, WANG Ze, ZHOU Yali, LI Jing, LU Xilan, BAI Hongwei, SHI Yuhua. Clinical effects of body mass index on ovulation induction treatment with letrozole among women with polycystic ovary syndrome [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(5): 81-85.
[12] LI Chang, ZHANG Qian, MA Fang, XIE Qi, CHANG Xiaotian. Relationship between PADI2 and genetic susceptibility in various human tumors [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(11): 47-53.
[13] LI Jingbo, LIU Hongbin, JIA Yueyue, WANG Ze, SUN Mei, SHI Yuhua. Expression and clinical significance of microRNA-183 in polycystic ovary syndrome with insulin resistance [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(1): 69-74.
[14] YANG Dongzi, MAI Zhuoyao. Features of ovarian reserve and outcomes of assisted reproductive technology in elder patients with PCOS [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(1): 26-32.
[15] ZHANG Lin, LI Jing, WANG Ze, ZHANG Jiangtao, MA Zengxiang, SHI Yuhua. Impact of thyroid-stimulating hormone on blood glucose and serum lipids in patients with polycystic ovary syndrome [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(1): 80-84.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] SHI Shuang, LI Juan, MI Qi, WANG Yunshan, DU Lutao, WANG Chuanxin. Construction and application of a miRNAs prognostic risk assessment model of gastric cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 47 -52 .
[2] LYU Longfei, LI Lin, LI Shuhai, QI Lei, LU Ming, CHENG Chuanle, TIAN Hui. Application of laparoscopic fine needle catheter jejunostomy in minimally invasive McKeown resection of esophageal cancer[J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 77 -81 .
[3] SHAO Haigang, WANG Xuan, WANG Qing. Anatomy of the root canal system of mandibular first premolar in population of Shandong Province[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(9): 85 -89 .
[4] HUANG Fei,WANG Huaijing,XING Yi,GAO Wei,LI Yonggang,XING Ziying,LI Zhenzhong. Protective effects of NGF and GM1 on primary sensory neurons in SD rat with sciatic nerve injury[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(4): 332 -335 .
[5] LI Yu-liang,WANG Yong-zheng,WANG Xiao-hua,ZHANG Fu-jun,ZHU Li-dong,ZHANG Wang-ming,LI Zheng,LI Zhen-jia,ZHANG Kai-xian. I implantation combined with Gemcitabine in the treatment of advanced pancreatic cancer[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(4): 393 -396 .
[6] LI Wei,LI Dao-wei,YE Qian,GAO Shun-cui,JIANG Shu-juan.

Diagnostic value of transbronchial needle aspiration in paratracheal mediastinal lesions

[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(11): 1063 -1065 .
[7] JIANG Bao-dong,MA Xiang-xing,WANG Qing,WANG Qian,FENG Xiao-yuan,LI Ke,YU Fu-hua. Imaging parameters of multislice spiral CT venography in cerebral veins[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(11): 1084 -1086 .
[8] WANG Xiaoju1, WANG Mingming2, XU Wansu2, ZHAO Shengmei3,CUI Sunan2, LI Xiaoying2, LIU Chunhua1
. Expression of peripheral blood lymphocyte ubiquitin mRNA in chronic HBV infection with active inflammation and its clinical significance[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2009, 47(02): 58 -61 .
[9] WANG Xu-ping,ZHAO Ling,FENG Yu-xin,SHANG Lin-shan,LIU Jin-cheng,. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(6): 564 -567 .
[10] WANG Xue-ping,YANG Hong-ling. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, (2): 213 .