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Volume 21, Issue 2 (March 2019) 21, 121–130; 10.4103/aja.aja_56_18

Proteomic analysis reveals dysregulated cell signaling in ejaculated spermatozoa from infertile men

Luna Samanta1,2, Rakesh Sharma1, Zhihong Cui1,3, Ashok Agarwal1

1 American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH 44195, USA
2 Department of Zoology, School of Life Sciences, Ravenshaw University, Cuttack, Odisha 753003, India
3 Institute of Toxicology, The Third Military Medical University, Chongqing 400038, China

Correspondence: Dr. Ashok Agarwal (agarwaa@ccf.org)

Date of Submission 20-Dec-2017 Date of Acceptance 13-Jun-2018 Date of Web Publication 26-Oct-2018


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.

Keywords: androgen receptor; chaperone; immature sperm; infertile men; proteasome; spermatozoa

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