1.Proteomic analysis reveals dysregulated cell signaling in ejaculated spermatozoa from infertile men.
Luna SAMANTA ; Rakesh SHARMA ; Zhihong CUI ; Ashok AGARWAL
Asian Journal of Andrology 2019;21(2):121-130
Dysfunctional sperm maturation is the primary reason for the poor sperm motility and morphology in infertile men. Spermatozoa from infertile men were fractioned on three-layer density gradient (80%, 60%, and 40%). Fraction 1 (F1) refers to the least mature stage having the lowest density, whereas the fraction 4 (F4) includes the most dense and morphologically mature motile spermatozoa. Fraction 2 (F2) and fraction 3 (F3) represent the intermediate stages. Proteins were extracted and separated by 1-dimensional gel. Bands were digested with trypsin and analyzed on a LTQ-Orbitrap Elite hybrid mass spectrometer system. Functional annotations of proteins were obtained using bioinformatics tools and pathway databases. A total of 1585 proteins were detected in the four fractions of spermatozoa. A dysregulated protein turnover and protein folding may lead to accumulation of defective proteins or proteins that otherwise would have been eliminated during the process of maturation, resulting in the impairment of sperm function. Aberrant chaperone expression may be a major contributing factor to the defective sperm function. Androgen receptor was predicted as a transcription regulator in one of the networks and the affected pathways were chaperone-mediated stress response, proteosomal pathway, and sperm function. The downregulation of key pathways and proteins which compromises the fertilizing potential of spermatozoa may provide insight into the mechanisms that lead to male infertility.
Adult
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Cell Shape/physiology*
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Humans
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Infertility, Male/metabolism*
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Male
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Proteome/metabolism*
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Proteomics
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Signal Transduction/physiology*
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Sperm Motility/physiology*
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Spermatozoa/metabolism*
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Tandem Mass Spectrometry
2.Knockout of glutathione peroxidase 5 down-regulates the piRNAs in the caput epididymidis of aged mice.
Chen CHU ; Lu YU ; Joelle HENRY-BERGER ; Yan-Fei RU ; Ayhan KOCER ; Alexandre CHAMPROUX ; Zhi-Tong LI ; Miao HE ; Sheng-Song XIE ; Wu-Bin MA ; Min-Jie NI ; Zi-Mei NI ; Yun-Li GUO ; Zhao-Liang FEI ; Lan-Tao GOU ; Qiang LIU ; Samanta SHARMA ; Yu ZHOU ; Mo-Fang LIU ; Charlie Degui CHEN ; Andrew L EAMENS ; Brett NIXON ; Yu-Chuan ZHOU ; Joël R DREVET ; Yong-Lian ZHANG
Asian Journal of Andrology 2020;22(6):590-601
The mammalian epididymis not only plays a fundamental role in the maturation of spermatozoa, but also provides protection against various stressors. The foremost among these is the threat posed by oxidative stress, which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids, proteins, and nucleic acids. In mice, the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5 (GPX5) as a major luminal scavenger in the proximal caput epididymidal segment. Accordingly, the loss of GPX5-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx5