Journal of Shandong University (Health Sciences) ›› 2019, Vol. 57 ›› Issue (1): 48-54.doi: 10.6040/j.issn.1671-7554.0.2018.726

Previous Articles    

Expression of polycystic ovary syndrome susceptibility gene dennd1a in zebrafish models

LIU Congcong, LIU Hongbin, FU Jiang, LI Lei   

  1. Center for Reproductive Medicine, Shandong University;
    National Research Center for Assisted Reproductive Technology and Reproductive Genetics;
    Key Laboratory for Reproductive Endocrinology (Shandong University), Ministry of Education;
    Shandong Provincial Key Laboratory of Reproductive Medicine, Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Jinan 250001, Shandong, China
  • Published:2022-09-27

Abstract: Objective To study the expression characteristics of polycystic ovary syndrome(PCOS)susceptibility gene dennd1a in developing embryos and in adult organs of zebrafish, and to establish zebrafish models for studies of the mechanisms underlying PCOS. Methods Using reverse transcription-polymerase chain reaction(RT-PCR)and real-time fluorescence quantitative reverse transcription polymerase chain reaction(qRT-PCR)techniques, we detected the expression of dennd1a in zebrafish. We also determined the expression pattern of dennd1a gene in zebrafish embryos using whole-mount in situ hybridization(WISH)assays. Results In embryos and juveniles, the expression level of dennd1a increased with age, and in adult animals, the expression was found in different organs. qRT-PCR and WISH showed the expression of dennd1a especially in the nervous system and male reproductive system. Conclusion In early stages of zebrafish development, high expression of dennd1a was found in the nervous system and male reproductive system, indicating this gene may regulate the development and function of the endocrine system and interrupt androgen synthesis and release, thereby inducing PCOS.

Key words: Polycystic ovary syndrome, dennd1a, Gene expression, Zebrafish, Animal models

CLC Number: 

  • R711.75
[1] Li R, Zhang Q, Yang D, et al. Prevalence of polycystic ovary syndrome in women in China: a large community-based study[J]. Hum Reprod, 2013, 28(9): 2562-2569.
[2] Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome[J]. Clin Epidemiol, 2013, 6: 1-13. doi: 10.2147/CLEP.S37559.
[3] Chen ZJ, Zhao H, He L, et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3[J]. Nat Genet, 2011, 43(1): 55-59.
[4] Mcallister JM, Legro RS, Modi BP, et al. Functional genomics of PCOS: from GWAS to molecular mechanisms[J]. Trends Endocrinol Metab, 2015, 26(3): 118-124.
[5] Cauvin C, Rosendale M, Gupta-Rossi N, et al. Rab35 GTPase triggers switch-like recruitment of the lowe syndrome lipid phosphatase OCRL on newborn endosomes[J]. Curr Biol, 2016, 26(1): 120-128.
[6] Goodarzi MO, Jones MR, Li X, et al. Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts[J]. J Med Genet, 2012, 49(2): 90-95.
[7] Udhane SS, Fluck CE. Regulation of human(adrenal)androgen biosynthesis-New insights from novel throughput technology studies[J]. Biochem Pharmacol, 2016, 102: 20-33. doi: 10.1016/j.bcp.2015.10.010.
[8] 孙梅, 盛燕, 马增香,等. 多囊卵巢综合征易感基因与代谢表型相关性分析[J]. 中华妇产科杂志, 2014, 49(6): 441-445. SUN Mei, SHENG Yan, MA Zengxiang, et al. Correlation analysis between polycystic ovary syndrome susceptibility genes and metabolic phenotypes[J]. Chinese Journal of Obstetrics and Gynecology, 2014, 49(6): 441-445.
[9] Dunaif A. Perspectives in polycystic ovary syndrome: from hair to eternity[J]. J Clin Endocrinol Metab, 2016, 101(3): 759-768.
[10] Zhao H, Xu X, Xing X, et al. Family-based analysis of susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3[J]. Hum Reprod, 2012, 27(1): 294-298.
[11] Eriksen MB, Nielsen MF, Brusgaard K, et al. Genetic alterations within the DENND1A gene in patients with polycystic ovary syndrome(PCOS)[J]. PLoS One, 2013, 8(9): e77186. doi: 10.1371/journal.pone.0077186.
[12] Bao S, Cai JH, Yang SY, et al. Association of DENND1A gene polymorphisms with polycystic ovary syndrome: a meta-analysis[J]. J Clin Res Pediatr Endocrinol, 2016, 8(2): 135-143.
[13] Rinkwitz S, Mourrain P, Becker TS. Zebrafish: an integrative system for neurogenomics and neurosciences[J]. Prog Neurobiol, 2011, 93(2): 231-243.
[14] Iwanami N. Zebrafish as a model for understanding the evolution of the vertebrate immune system and human primary immunodeficiency[J]. Exp Hematol, 2014, 42(8): 697-706.
[15] Hoo JY, Kumari Y, Shaikh MF, et al. Zebrafish: a versatile animal model for fertility research[J]. Biomed Res Int, 2016, 2016: 9732780. doi: 10.1155/2016/9732780.
[16] Yildiz BO, Bozdag G, Yapici Z, et al. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria[J]. Hum Reprod, 2012, 27(10): 3067-3073.
[17] 李婧博,刘洪彬,贾月月,等. microRNA-183在PCOS胰岛素抵抗中的表达及其临床意义[J]. 山东大学学报(医学版), 2017, 55(1): 69-74. LI Jingbo, LIU Hongbin, JIA Yueyue, et al. 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.
[18] Chen L, Hu LM, Wang YF, et al. Genome-wide association study for SNPs associated with PCOS in human patients[J]. Exp Ther Med, 2017, 14(5): 4896-4900.
[19] Ha L, Shi Y, Zhao J, et al. Association Study between Polycystic Ovarian Syndrome and the Susceptibility Genes Polymorphisms in Hui Chinese Women[J]. PLoS One, 2015, 10(5): e126505. doi: 10.1371/journal.pone.0126505.
[20] Gammoh E, Arekat MR, Saldhana FL, et al. DENND1A gene variants in Bahraini Arab women with polycystic ovary syndrome[J]. Gene, 2015, 560(1): 30-33.
[21] Saxena R, Georgopoulos NA, Braaten TJ, et al. Han Chinese polycystic ovary syndrome risk variants in women of European ancestry: relationship to FSH levels and glucose tolerance[J]. Hum Reprod, 2015, 30(6): 1454-1459.
[22] 彭丹红,罗嘉莉,凌丽,等. DENND1A基因多态性与多囊卵巢综合征易感性的Meta分析[J]. 南京医科大学学报(自然科学版), 2017, 37(10): 1362-1368. PENG Danhong, LUO Jiali, LING Li, et al. Meta-analysis on relationship between DENND1A polymorphisms and polycystic ovary syndrome[J]. Journal of Nanjing Medical University(Natural Sciences), 2017, 37(10): 1362-1368.
[23] Dallel M, Sarray S, Douma Z, et al. Differential association of DENND1A genetic variants with polycystic ovary syndrome in Tunisian but not Bahraini Arab women[J]. Gene, 2018, 647: 79-84. doi: 10.1016/j.gene.2018.01.028.
[24] Tee MK, Speek M, Legeza B, et al. Alternative splicing of DENND1A, a PCOS candidate gene, generates variant 2[J]. Mol Cell Endocrinol, 2016, 434: 25-35. doi: 10.1016/j.mce.2016.06.011.
[25] Mcallister JM, Modi B, Miller BA, et al. Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype[J]. Proc Natl Acad Sci U S A, 2014, 111(15): E1519-E1527.
[26] Cui L, Li G, Zhong W, et al. Polycystic ovary syndrome susceptibility single nucleotide polymorphisms in women with a single PCOS clinical feature[J]. Hum Reprod, 2015, 30(3): 732-736.
[27] Wang Z, Li T, Zhang W, et al. Variants in DENND1A and LHCGR are associated with endometrioid adenocarcinoma[J]. Gynecol Oncol, 2012, 127(2): 403-405.
[28] Lee AP, Brenner S, Venkatesh B. Mouse transgenesis identifies conserved functional enhancers and cis-regulatory motif in the vertebrate LIM homeobox gene Lhx2 locus[J]. PLoS One, 2011, 6(5): e20088. doi: 10.1371/journal.pone.0020088.
[29] Marat AL, Mcpherson PS. The connecdenn family, Rab35 guanine nucleotide exchange factors interfacing with the clathrin machinery[J]. J Biol Chem, 2010, 285(14): 10627-10637. doi: 0.1074/jbc.M109.050930.
[30] Kent SC, Gnatuk CL. Hyperandrogenism and hyperinsulinism in children of women with polycystic ovary syndrome: a controlled study[J]. J Clin Endocrinol Metab, 2008, 93(5): 1662-1669.
[31] Leibel NI, Baumann EE. Relationship of adolescent polycystic ovary syndrome to parental metabolic syndrome[J]. J Clin Endocrinol Metab, 2006, 91(4): 1275-1283.
[32] Recabarren SE, Smith R. Metabolic profile in sons of women with polycystic ovary syndrome[J]. J Clin Endocrinol Metab, 2008, 93(5): 1820-1826.
[33] Torvinen A, Koivunen R. Metabolic and reproductive characteristics of first-degree relatives of women with self-reported oligo-amenorrhoea and hirsutism[J]. Gynecol Endocrinol, 2011, 27(9): 630-635.
[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] HAN Xiao, LI Lei, LIU Congcong. Effect of testosterone on the expression of polycystic ovary syndrome susceptibility gene Tox3 in zebrafish [J]. Journal of Shandong University (Health Sciences), 2021, 59(4): 42-47.
[3] 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.
[4] 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.
[5] 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.
[6] ZHANG Shuying, WU Xiaofeng, GUO Limin, QIAO Wen, PENG Jieqiong, LI Daqing. Evaluation of two doxorubicin-induced heart failure models and changes of cardiac function [J]. Journal of Shandong University (Health Sciences), 2020, 58(12): 1-7.
[7] 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.
[8] 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.
[9] HU Yujing, WU Dayong, ZHANG Wenyan, BIAN Yanzhu, WEI Qiang, TIAN Congna, CHANG Shengli. Correlation between 99Tcm-MNLS hypoxic scintigraphy and hypoxia-inducible factor-1α after radiotherapy [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(8): 30-34.
[10] 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.
[11] 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.
[12] 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.
[13] JIA Yueyue, LIU Hongbin, LI Jingbo, LI Jing, ZHANG Jiangtao, SUN Mei, SHI Yuhua. Expression of microRNA-200b in granulosa cells of PCOS patients and its significance [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2017, 55(1): 63-68.
[14] 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.
[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   
No Suggested Reading articles found!