Abstract
BackgroundThe 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.MethodsThe 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.ResultsWe 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.ConclusionsThe 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.
Highlights
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
Some mouse beta-defensin genes have other aliases or designations; for example, Defb41 is known as Defb16, Defb19 is known as Defb24, Defb45 is known as Defb27, Defb42 is known as Defb44, and Spag11a is known as Ep2e, Bin1b or Spag11
Androgen regulation of beta-defensin gene expression in the mouse caput epididymidis To investigate the transcriptional regulation of beta-defensin genes, we analyzed the expression of these genes in gonadectomized mice
Summary
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. 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 demonstrated homozygous males with low motility sperm and a reduced fertility phenotype [10]. Recent studies have further enhanced our understanding of the role of beta-defensins in fertility and sterility. Tollner et al reported that a common mutation in the human defensin Defb126 causes reduced sperm penetration ability and is associated with subfertility [12]
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