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山东大学学报 (医学版) ›› 2021, Vol. 59 ›› Issue (4): 42-47.doi: 10.6040/j.issn.1671-7554.0.2021.0056

• 基础医学 • 上一篇    下一篇

睾酮对于多囊卵巢综合征易感基因Tox3表达的影响

韩笑,李雷,刘聪聪   

  1. 山东大学生殖医学研究中心(山东大学附属生殖医院)生殖内分泌教育部重点实验室 山东省生殖医学重点实验室 国家辅助生殖与优生工程技术研究中心, 山东 济南 250001
  • 发布日期:2021-04-30
  • 通讯作者: 李雷. E-mail:201596000004@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(81671242)

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

摘要: 目的 确定多囊卵巢综合征(PCOS)易感基因Tox3在野生型斑马鱼模型中的表达模式,探讨睾酮对于Tox3基因表达的影响。 方法 取斑马鱼胚胎约200枚与雌雄成年斑马鱼各约100条进行对照处理及睾酮(10 ng/mL)处理,利用反转录-聚合酶链反应(RT-PCR)及实时荧光定量逆转录聚合酶链反应(qRT-PCR)技术,检测各组斑马鱼中Tox3基因的表达特性。采用胚胎整体原位杂交(WISH)方法,在数枚斑马鱼胚胎内定位观察Tox3基因的表达以及分布。 结果 野生型斑马鱼的神经系统和生殖系统中Tox3基因表达水平较高与对照组相比,雄性斑马鱼Tox3的表达在10 ng/mL睾酮处理后的精巢[(1.05±0.32) vs(1.50±0.30), P=0.015及脑[(1.01±0.19)vs(1.43±0.35), P=0.043中均升高。 结论 斑马鱼Tox3基因可能通过作用于神经内分泌系统,参与雄激素合成。

关键词: 睾酮, 多囊卵巢综合征, Tox3, 基因表达, 斑马鱼

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

中图分类号: 

  • 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.
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