Androgenic regulation of beta-defensins in the mouse epididymis
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RESEARCH
Open Access
Androgenic regulation of beta-defensins in the mouse epididymis Shuang-Gang Hu1,2, Mei Zou2, Guang-Xin Yao2, Wu-Bin Ma2, Qin-Ling Zhu1, Xiang-Qi Li2, Zi-Jiang Chen1 and Yun Sun1*
Abstract 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. Keywords: Androgen, Androgen receptor, Epididymis, Beta-defensins
Background Beta-defensins are small cationic peptides that exhibit broad-spectrum antimicrobial properties and contribute to mucosal immune responses at epithelial sites. Recently, the complete genome sequences of different species and computational prediction and experimental verification have identified 30–50 novel beta-defensin genes in humans, rats and mice that are organized into gene clusters localized at specific chromosomes [1,2]. The mRNAs encoding the majority of beta-defensins are exclusively expressed in the epididymis [3,4]. Epididymal beta-defensins with * Correspondence: [email protected] 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 Full list of author in
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