Differential Expression and Antibacterial Activity of Epididymis Protein 2 Isoforms in the Male Reproductive Tract of Human and Rhesus Monkey (Macaca mulatta)1

Avellar, Maria Christina W.; Honda, Luciana; Hamil, Katherine G.; Yenugu, Suresh; Grossman, Gail; Petrusz, Peter; French, Frank S.; Hall, Susan H.

doi:10.1095/biolreprod.104.031740

Cited by 36 publications

(30 citation statements)

References 43 publications

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“…MUC15 overexpression in colorectal carcinoma cells enhances cell proliferation, cell extracellular matrix adhesion, colony-forming ability, and invasion (37). SPAG11B is a cationic secretory anti-microbial peptide expressed in human epididymis (38,39). FAM12B is an epididymal secretory protein (40,41) that has been found up-regulated in epididymides of nonobstructive azoospermic men (42).…”

Section: Discussionmentioning

confidence: 99%

Verification of Male Infertility Biomarkers in Seminal Plasma by Multiplex Selected Reaction Monitoring Assay

Drabovich

Jarvi

Diamandis

2011

Molecular & Cellular Proteomics

102

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Seminal plasma is a promising biological fluid to use for noninvasive clinical diagnostics of male reproductive system disorders. To verify a list of prospective male infertility biomarkers, we developed a multiplex selected reaction monitoring assay and measured the relative abundance of 31 proteins in 30 seminal plasma samples from normal, nonobstructive azoospermia and post-vasectomy individuals. Median levels of some proteins were decreased by more than 100-fold in nonobstructive azoospermia or post-vasectomy samples, in comparison with normal samples. To follow up the most promising candidates and measure their concentrations in seminal plasma, heavy isotope-labeled internal standards were synthesized and used to reanalyze 20 proteins in the same set of samples. Concentrations of candidate proteins in normal seminal plasma were found in the range 0.1-1000 g/ml but were significantly decreased in nonobstructive azoospermia and post-vasectomy. These data allowed us to select, for the first time, biomarkers to discriminate between normal, nonobstructive azoospermia, and post-vasectomy (simulated obstructive azoospermia) seminal plasma samples. Some testis-specific proteins (LDHC, TEX101, and SPAG11B) performed with absolute or nearly absolute specificities and sensitivities. Cell-specific classification of protein expression indicated that Sertoli or germ cell dysfunction, but not Leydig cell dysfunction, was observed in nonobstructive azoospermia seminal plasma. The proposed panel of biomarkers, pending further validation, could lead to a clinical assay that can eliminate the need for testicular biopsy to diagnose the category of male infertility, thus providing significant benefits to patients as well as decreased costs associated with the differential diagnosis of azoospermia. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.004127, 1-13, 2011.Human infertility affects ϳ15% of couples, with the male contributing to the infertility in 50% of all cases (1, 2). One of the most severe forms of male infertility is azoospermia, which is characterized by an absence of sperm in the semen (3). Azoospermia is diagnosed in 20% of subfertile men and has two forms: obstructive azoospermia (OA) 1 and nonobstructive azoospermia (NOA). OA is caused by a physical obstruction in the male reproductive tract. The biological outcome of OA is thus identical to that of vasectomy, which is a surgical severance of the vas deferens. NOA is a more complicated infertility syndrome with the azoospermia being secondary to a failure to produce sperm; NOA may be further subclassified as maturation arrest, Sertoli cell-only syndrome, and hypospermatogenesis (4).For most men with azoospermia, testicular biopsy is the only currently used method to definitively distinguish between OA and NOA (5, 6). Thus, there is an urgent need for an alternative noninvasive approach with better diagnostic potential. The differential diagnosis of normal, NOA, and OA (or post-vasectomy (PV)) men is required for the following reasons: (i) in infertile pati...

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Section: Discussionmentioning

confidence: 99%

Verification of Male Infertility Biomarkers in Seminal Plasma by Multiplex Selected Reaction Monitoring Assay

Drabovich

Jarvi

Diamandis

2011

Molecular & Cellular Proteomics

102

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“…This response involves the secretion of cytokines and antibacterial substances, such as b-defensins (Froy 2005, Kogut et al 2006. TLRs and b-defensins have been identified as the key components of innate immune recognition in the reproductive tract of male vertebrate species, providing the first line of defense against potential pathogens (Li et al 2001, Com et al 2003, Palladino et al 2003, Avellar et al 2004, Nishimura & Naito 2005, Rodrigues et al 2008, Anastasiadou et al 2011. Cytokines are essential for the activation, differentiation, and control of the immune system and also play a key role in initiating innate and adaptive immune responses (Hiscott & Ware 2011).…”

Section: Introductionmentioning

confidence: 99%

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

Michailidis¹,

Anastasiadou²,

Guibert³

et al. 2014

Reproduction

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Sertoli cells (SCs) play an important physiological role in the testis, as they support, nourish, and protect the germ cells. As protection of the developing spermatozoa is an emerging aspect of reproductive physiology, this study examined the expression pattern of innate immune-related genes, including avian b-defensins (AvBDs), Toll-like receptors (TLRs), and cytokines, and investigated the time course of an inflammatory response in rooster SCs triggered by exposure to the bacterial endotoxin lipopolysaccharide (LPS). SCs were isolated from 6-week-old chicken, cultured in vitro, and stimulated with 1 mg/ml LPS at different time courses (0, 6, 12, 24, and 48 h). Data on expression analysis revealed that all ten members of the chicken TLR family, nine members of the AvBD family, as well as eight cytokine genes were expressed in SCs. Quantitative real-time PCR analysis revealed that LPS treatment resulted in significant induction of the expression levels of six TLRs, six AvBDs, and four cytokine genes, while two cytokine genes were downregulated and two other genes were unchanged. The increasing interleukin 1b (IL1b) production was confirmed in the conditioned medium. Furthermore, the phagocytosis of SCs was increased after LPS treatment. In conclusion, these findings provide evidence that SCs express innate immunerelated genes and respond directly to bacterial ligands. These genes represent an important component of the immune system, which could be integrated into semen, and present a distinctive constituent of the protective repertoire of the testis against ascending infections.

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“…3,4,11 In addition, the b-defensin-like epididymal protein (EP2)/sperm-associated antigen 11 (SPAG11) isoforms are also predominantly expressed in the male reproductive tract. 12 Recent studies specifically implicate b-defensins in pivotal roles in reproductive biology including ESP13.2/DEFB126 in sperm capacitation 13 and Bin1b/EP2E in sperm maturation, 14 thereby redefining our concepts concerning the multifunctional roles of b-defensins.…”

Section: Introductionmentioning

confidence: 99%

Identification, characterization, and evolution of a primate β-defensin gene cluster

et al. 2005

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Defensins are members of a large diverse family of cationic antimicrobial peptides that share a signature pattern consisting of six conserved cysteine residues. Defensins have a wide variety of functions and their disruption has been implicated in various human diseases. Here we report the characterization of DEFB119-DEFB123, five genes in the human b-defensin cluster locus on chromosome 20q11.1. The genomic structures of DEFB121 and DEFB122 were determined in silico. Sequences of the five macaque orthologs were obtained and expression patterns of the genes were analyzed in humans and macaque by semiquantitative reverse transcription polymerase chain reaction. Expression was restricted to the male reproductive tract. The genes in this cluster are differentially regulated by androgens. Evolutionary analyses suggest that this cluster originated by a series of duplication events and by positive selection. The evolutionary forces driving the proliferation and diversification of these defensins may be related to reproductive specialization and/or the host-parasite coevolutionary process.

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Differential Expression and Antibacterial Activity of Epididymis Protein 2 Isoforms in the Male Reproductive Tract of Human and Rhesus Monkey (Macaca mulatta)1

Cited by 36 publications

References 43 publications

Verification of Male Infertility Biomarkers in Seminal Plasma by Multiplex Selected Reaction Monitoring Assay

Verification of Male Infertility Biomarkers in Seminal Plasma by Multiplex Selected Reaction Monitoring Assay

Activation of innate immune system in response to lipopolysaccharide in chicken Sertoli cells

Identification, characterization, and evolution of a primate β-defensin gene cluster

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