Identification of sperm forward motility‐related proteins in human seminal plasma

Ding, Zhide; Qü, Fei; Guo, Wei; Ying, Xiaoqian; Wu, Minxian; Zhang, Yonglian

doi:10.1002/mrd.20624

Cited by 40 publications

(35 citation statements)

References 48 publications

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“…In a previous study, we reported that ZAG was primarily related to sperm forward motility in human semen (Ding et al 2007). Our data supported the fact that ZAG in human seminal plasma might be integrated with a-1-antitrypsin (AAT) and was capable of initiating forward motility in immature immotile spermatozoa.…”

Section: Introductionsupporting

confidence: 86%

The role of Zn-α2 glycoprotein in sperm motility is mediated by changes in cyclic AMP

Qü¹,

Ying²,

Guo³

et al. 2007

Reproduction

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Sperm motility is essential for male reproduction or natural fertilization. The cyclic AMP (cAMP)/cAMP-dependent protein kinase A (PKA) signaling pathway is generally recognized as one of the significant signaling pathways in the regulation of mammalian spermatozoan motility. Since Zn-a2-glycoprotein (ZAG) activity in mammalian adipose tissue is mediated via the b 3 -adrenoreceptor, with upregulation of the cAMP pathway, we hypothesize that ZAG may play the same role in sperm motility regulation, a new factor of regulation of sperm motility. Therefore, the gene encoding human ZAG was cloned and polyclonal antibodies were generated, and then laser scanning confocal microscopy and flow cytometry were employed to identify this protein in human spermatozoa. The results showed that ZAG protein was mostly localized on the pre-equatorial region covering the acrosome, neck, and middle piece of the flagellum of spermatozoa. Furthermore, using computer-assisted sperm analysis, we found that anti-human ZAG antibodies could significantly reduce the motility of human swim-up spermatozoa after 90-or 120-min incubation (P!0.05 and P!0.01 respectively), together with the decreasing of intracellular cAMP and PKA levels. In conclusion, these data suggest that ZAG is present in human spermatozoa and may be involved in the regulation of sperm motility via the cAMP/PKA signaling pathway.

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Section: Introductionsupporting

confidence: 86%

The role of Zn-α2 glycoprotein in sperm motility is mediated by changes in cyclic AMP

Qü¹,

Ying²,

Guo³

et al. 2007

Reproduction

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“…Moreover, our endpoint in this study was seminal alteration per se, which makes it necessary to perform a confirmatory prospective multicentric cohort study in order to validate our findings, as well as to better define cutoff values. Finally, it is important to better understand the role of seminal plasma proteins in different causes of infertility, because this is a promising field that can indicate potential biomarkers, and because the regulatory activity of extracellular proteins in seminal plasma is fundamental for proper sperm function after ejaculation [48].…”

Section: Discussionmentioning

confidence: 99%

Alterations in the proliferative/apoptotic equilibrium in semen of adolescents with varicocele

Belardin

Giudice

Camargo

et al. 2016

J Assist Reprod Genet

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Purpose To verify if the presence of varicocele (grades II and III) with and without seminal alterations, using the 5 th centile cutoff values in table A1.1 of the World Health Organization (WHO, 2010) manual, alters the seminal plasma levels of proteins DNASE1 (deoxyribonuclease-1) and IGFBP7 (Insulin-like growth factor-binding protein 7), which are related to apoptosis regulation and cell proliferation, respectively, demonstrating that these proteins are important for correct spermatogenesis. Methods This cross sectional study was performed at the Sao Paulo Federal University Paulo between May 2014 and April 2016. A total of 61 male adolescents were included in this study, of which 20 controls without varicocele (C), 22 with varicocele and normal semen analysis (VNS) and 19 with varicocele and altered semen analysis (VAS). Seminal plasma from each patient was used for Western blotting analysis of individual protein levels. Values of each protein were normalized to a testicular housekeeping protein (PARK7-protein deglycase DJ-1). Results Levels of IGFBP7 protein are increased in varicocele. Levels of DNASE1 are progressively decreased in varicocele (lower in varicocele and normal semen analysis, lowest in varicocele and altered semen analysis) when compared to adolescents without varicocele. DNASE1 levels are positively correlated with sperm concentration and morphology (correlation values of 0.400 and 0.404, respectively; p values of 0.001 and 0.001, respectively). Conclusion In conclusion, in adolescents, seminal plasma levels of IGFBP7, responsible for proliferative activity, are increased in varicocele grades II and III, and DNASE1, responsible for apoptosis regulation, are lower in varicocele, lowest in varicocele and low semen quality. These proteins demonstrate molecular alterations brought upon by varicocele. Moreover, DNASE1 is capable of discriminating a varicocele that causes alterations to semen quality from one that does not. We propose that the initial response of varicocele is to increase proliferative activity which, if followed by regulation of apoptosis, may lead to the ejaculation of a population of sperm that are in accordance with WHO cutoff values but, in the presence of dysregulated apoptosis, leads to lower sperm concentration and morphology.

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“…The seminal plasma ZAG is synthesized by prostate epithelial cells and secreted into seminal fluid (62), and it constitutes 30% of the proteins present in the seminal fluid (18). Hale et al (44) determined the expression of ZAG in prostate tumors and found that ZAG is produced by 73% of prostate cancers.…”

Section: Zag and Cancermentioning

confidence: 99%

“…The mechanisms by which cAMP activates sperm cytosolic cAMP, which in turn phosphorylates multiple intrasperm phosphoproteins that may regulate flagellar motility (112,113) of spermatozoa. Moreover, ZAG is also a protein that is directly related to sperm motility and in turn fertilization (62).…”

Section: Fertilizationmentioning

confidence: 99%

Zinc α2-Glycoprotein: A Multidisciplinary Protein

Hassan

Waheed

Yadav

et al. 2008

Molecular Cancer Research

216

204

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Zinc A2-glycoprotein (ZAG) is a protein of interest because of its ability to play many important functions in the human body, including fertilization and lipid mobilization. After the discovery of this molecule, during the last 5 decades, various studies have been documented on its structure and functions, but still, it is considered as a protein with an unknown function. Its expression is regulated by glucocorticoids. Due to its high sequence homology with lipid-mobilizing factor and high expression in cancer cachexia, it is considered as a novel adipokine. On the other hand, structural organization and fold is similar to MHC class I antigen-presenting molecule; hence, ZAG may have a role in the expression of the immune response. The function of ZAG under physiologic and cancerous conditions remains mysterious but is considered as a tumor biomarker for various carcinomas. There are several unrelated functions that are attributed to ZAG, such as RNase activity, regulation of melanin production, hindering tumor proliferation, and transport of nephritic by-products. This article deals with the discussion of the major aspects of ZAG from its gene structure to function and metabolism. (Mol Cancer Res 2008;6(6):892 -906)

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Identification of sperm forward motility‐related proteins in human seminal plasma

Cited by 40 publications

References 48 publications

The role of Zn-α2 glycoprotein in sperm motility is mediated by changes in cyclic AMP

The role of Zn-α2 glycoprotein in sperm motility is mediated by changes in cyclic AMP

Alterations in the proliferative/apoptotic equilibrium in semen of adolescents with varicocele

Zinc α2-Glycoprotein: A Multidisciplinary Protein

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