Reproductive Biology and Endocrinology | |
Androgenic regulation of beta-defensins in the mouse epididymis | |
Yun Sun1  Zi-Jiang Chen1  Xiang-Qi Li2  Qin-Ling Zhu1  Wu-Bin Ma2  Guang-Xin Yao2  Mei Zou2  Shuang-Gang Hu2  | |
[1] Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China;Shanghai Key Laboratory for Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200030, China | |
关键词: Beta-defensins; Epididymis; Androgen receptor; Androgen; | |
Others : 1139779 DOI : 10.1186/1477-7827-12-76 |
|
received in 2014-04-28, accepted in 2014-08-01, 发布年份 2014 | |
【 摘 要 】
Background
The majority of beta-defensin family members are exclusively expressed in the epididymis, and some members have been shown to play essential roles in sperm maturation and fertility in rats, mice and humans. Therefore, beta-defensins are hypothesized to be potential targets for contraception and infertility diagnosis and treatment. Clarifying the regulatory mechanisms for the expression of these genes is necessary. Androgen/androgen receptor (AR) signaling plays an important regulatory role in epididymal structure and function. However, very little is known about the androgenic regulation on the production and secretion of the epididymal beta-defensins.
Methods
The expression of beta-defensins was detected by quantitative RT-PCR. The androgen dependence of beta-defensins was determined by bilateral orchiectomy and androgen supplementation. The androgen response elements (AREs) in the promoters of beta-defensins were identified using the MatInspector software. The binding of AR to AREs was assayed by ChIP-PCR/qPCR.
Results
We demonstrated that 23 mouse caput epididymal beta-defensins were differentially regulated by androgen/androgen receptor. Six genes, Defb18, 19, 20, 39, 41, and 42, showed full regulation by androgens. Ten genes, Defb15, 30, 34, 37, 40, 45, 51, 52, 22 and Spag11a, were partially regulated by androgens. Defb15, 18, 19, 20, 30, 34, 37, 39, 41, 42, 22 and Spag11a were associated with androgen receptor binding sites in their promoter or intronic regions, indicating direct regulation of AR. Six genes, Defb1, 12, 13, 29, 35, and spag11b/c, exhibited an androgen-independent expression pattern. One gene, Defb25, was highly dependent on testicular factors rather on androgens.
Conclusions
The present study provides novel insights into the mechanisms of androgen regulation on epididymal beta-defensins, enabling a better understanding of the function of beta-defensins in sperm maturation and fertility.
【 授权许可】
2014 Hu et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150322145641400.pdf | 750KB | download | |
Figure 3. | 103KB | Image | download |
Figure 2. | 92KB | Image | download |
Figure 1. | 121KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Patil AA, Cai Y, Sang Y, Blecha F, Zhang G: Cross-species analysis of the mammalian beta-defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract. Physiol Genomics 2005, 23(1):5-17.
- [2]Schutte BC, Mitros JP, Bartlett JA, Walters JD, Jia HP, Welsh MJ, Casavant TL, McCray PB Jr: Discovery of five conserved beta -defensin gene clusters using a computational search strategy. Proc Natl Acad Sci U S A 2002, 99(4):2129-2133.
- [3]Yamaguchi Y, Nagase T, Makita R, Fukuhara S, Tomita T, Tominaga T, Kurihara H, Ouchi Y: Identification of multiple novel epididymis-specific beta-defensin isoforms in humans and mice. J Immunol 2002, 169(5):2516-2523.
- [4]Zaballos A, Villares R, Albar JP, Martinez AC, Marquez G: Identification on mouse chromosome 8 of new beta-defensin genes with regionally specific expression in the male reproductive organ. J Biol Chem 2004, 279(13):12421-12426.
- [5]Diao H, Guo C, Lin D, Zhang Y: Intein-mediated expression is an effective approach in the study of beta-defensins. Biochem Biophys Res Commun 2007, 357(4):840-846.
- [6]Yenugu S, Hamil KG, Radhakrishnan Y, French FS, Hall SH: The androgen-regulated epididymal sperm-binding protein, human beta-defensin 118 (DEFB118) (formerly ESC42), is an antimicrobial beta-defensin. Endocrinology 2004, 145(7):3165-3173.
- [7]Zhao Y, Diao H, Ni Z, Hu S, Yu H, Zhang Y: The epididymis-specific antimicrobial peptide beta-defensin 15 is required for sperm motility and male fertility in the rat (Rattus norvegicus). Cell Mol Life Sci 2010, 68(4):697-708.
- [8]Zhou CX, Zhang YL, Xiao L, Zheng M, Leung KM, Chan MY, Lo PS, Tsang LL, Wong HY, Ho LS, Chung YW, Chan HC: An epididymis-specific beta-defensin is important for the initiation of sperm maturation. Nat Cell Biol 2004, 6(5):458-464.
- [9]Xu W, Zhang X, Chen W, Fok KL, Rowlands DK, Chui YL, Chan HC: Immunization with Bin1b decreases sperm motility with compromised fertility in rats. Fertil Steril 2010, 93(3):952-958. e951
- [10]Semple F, Dorin JR: Beta-Defensins: multifunctional modulators of infection, inflammation and more? J Innate Immun 2012, 4(4):337-348.
- [11]Zhou YS, Webb S, Lettice L, Tardif S, Kilanowski F, Tyrrell C, Macpherson H, Semple F, Tennant P, Baker T, Hart A, Devenney P, Perry P, Davey T, Barran P, Barratt CL, Dorin JR: Partial deletion of chromosome 8 beta-defensin cluster confers sperm dysfunction and infertility in male mice. PLoS Genet 2013, 9(10):e1003826.
- [12]Tollner TL, Venners SA, Hollox EJ, Yudin AI, Liu X, Tang G, Xing H, Kays RJ, Lau T, Overstreet JW, Xu X, Bevins CL, Cherr GN: A common mutation in the defensin DEFB126 causes impaired sperm function and subfertility. Sci Transl Med 2011, 3(92):92ra65.
- [13]Patrao MT, Silva EJ, Avellar MC: Androgens and the male reproductive tract: an overview of classical roles and current perspectives. Arq Bras Endocrinol Metabol 2009, 53(8):934-945.
- [14]Hu S, Yao G, Guan X, Ni Z, Ma W, Wilson EM, French FS, Liu Q, Zhang Y: Research resource: Genome-wide mapping of in vivo androgen receptor binding sites in mouse epididymis. Mol Endocrinol 2010, 24(12):2392-2405.
- [15]Jalkanen J, Huhtaniemi I, Poutanen M: Discovery and characterization of new epididymis-specific beta-defensins in mice. Biochim Biophys Acta 2005, 1730(1):22-30.
- [16]Oh J, Lee J, Woo JM, Choi E, Park I, Han C, Baek N, Lee H, Kim do H, Cho C: Systematic identification and integrative analysis of novel genes expressed specifically or predominantly in mouse epididymis. BMC genomics 2006, 7:314.
- [17]Pujianto DA, Loanda E, Sari P, Midoen YH, Soeharso P: Sperm-associated antigen 11A is expressed exclusively in the principal cells of the mouse caput epididymis in an androgen-dependent manner. Reprod Biol Endocrinol 2013, 11:59.
- [18]Johnston DS, Jelinsky SA, Bang HJ, DiCandeloro P, Wilson E, Kopf GS, Turner TT: The mouse epididymal transcriptome: transcriptional profiling of segmental gene expression in the epididymis. Biol Reprod 2005, 73(3):404-413.
- [19]Johnston DS, Turner TT, Finger JN, Owtscharuk TL, Kopf GS, Jelinsky SA: Identification of epididymis-specific transcripts in the mouse and rat by transcriptional profiling. Asian J Androl 2007, 9(4):522-527.
- [20]Robaire B, Seenundun S, Hamzeh M, Lamour SA: Androgenic regulation of novel genes in the epididymis. Asian J Androl 2007, 9(4):545-553.
- [21]Chauvin TR, Griswold MD: Androgen-regulated genes in the murine epididymis. Biol Reprod 2004, 71(2):560-569.
- [22]Semple CA, Rolfe M, Dorin JR: Duplication and selection in the evolution of primate beta-defensin genes. Genome Biol 2003, 4(5):R31.
- [23]Patki M, Chari V, Sivakumaran S, Gonit M, Trumbly R, Ratnam M: The ETS domain transcription factor ELK1 directs a critical component of growth signaling by the androgen receptor in prostate cancer cells. J Biol Chem 2013, 288(16):11047-11065.
- [24]Pihlajamaa P, Sahu B, Lyly L, Aittomäki V, Hautaniemi S, Jänne OA: Tissue-specific pioneer factors associate with androgen receptor cistromes and transcription programs. EMBO J 2014, 33(4):312-326.