Effect of transient scrotal hyperthermia on human sperm: an iTRAQ-based proteomic analysis

Abstract

Background Through this prospective study, we aimed to explore the change of molecular modification after the transient scrotal hyperthermia on human sperm. Methods Ten healthy subjects selected with strict screening criteria underwent testicular warming in a 43 °C water bath for 30 min a day for 10 consecutive days. Semen samples were collected 2 weeks before the first heat treatment and 6 weeks after the first heat treatment. Proteins from the samples were labeled with isobaric tags for relative and absolute quantitation and analyzed by two-dimensional liquid chromatography–tandem mass spectrometry. Results In contrast to the control, of the 3446 proteins identified, 61 proteins were deregulated: 28 were up-regulated and 33 were down-regulated. Approximately 95% of the differentially expressed proteins were found to participate in spermatogenesis, fertilization, or other aspects of reproduction. In particular, the expression of sperm motility and energy metabolism-related proteins AKAP4, SPESP1, ODF1, ODF2, GAPDHS, and ACTRT2, validated by western blotting of the proteins obtained from human and mouse samples, tended to be reduced under scrotal hyperthermia. Conclusions The results indicated that the proteins AKAP4, ODF1, ODF2, GAPDHS, SPESP1, and ACTRT2, play an important role in the heat-induced reversible reduction in sperm concentration and motility and have the potential to be the biomarkers and clinical targets for scrotal heat treatment induced male infertility.

Global warming and testis function: A challenging crosstalk in an equally challenging environmental scenario

“…In 2020, Wu et al aimed to investigate the molecular fingerprint of human spermatozoa exposed to acute heat stress through a proteomic approach ( Wu et al, 2020 ). Testicular warming at 43°C, administered through sessions of 30-min water bath/day for 10 consecutive days, was associated with the deregulation of more than 60 proteins at 6 weeks after the heat stress, most of which were involved in spermatogenesis, fertilization, or other aspects of reproduction.…”

“…The authors also found a similar pattern of deregulation upon the application of the same heat stress model in mice. In particular, significant downregulation was observed for the protein of A-kinase anchor protein 4 (AKAP4), involved in sperm motility and acrosome reaction, the cytoskeleton proteins’ outer dense fiber protein 1 (ODF1), testis-specific glyceraldehyde-3-phosphate dehydrogenase, (GAPDHS), sperm equatorial segment protein 1 (SPESP1), and actin-related protein T2 (ACTRT2) ( Cheng et al, 2014 ; Wu et al, 2020 ). On these bases, the authors argued that the deregulation of these proteins, closely associated with the reversible decrease in sperm viability and concentration, was mainly driven by heat stress ( Wu et al, 2020 ).…”

The Impact of High Ambient Temperature on Human Sperm Parameters: A Meta-Analysis

“…During spermatogenesis, the optimal temperature of the testicles is 2 to 4°C lower than body temperature ( 12 ). In 2020, Yan-Qing Wu showed that heat stress caused an increase in testicular tissue temperature, decreasing sperm concentration and motility in humans who experienced scrotal warming ( 13 ). Heat stress damages human sperm by reducing sperm motility and viability ( 14 ).…”

Effects of Heat Stress on Motion Characteristics and Metabolomic Profiles of Boar Spermatozoa

“…Transcriptome analysis revealed that the expression of multiple genes was altered in boars exposed to heat stress, and some differentially expressed genes were also identified between heat-tolerant and heat-susceptible boars [ 8 ]. Proteomic profiling showed that heat stress caused the differential expression of 60 and 85 proteins in human [ 9 ] and boar [ 10 ] sperm, respectively. Moreover, heat stress also severely perturbed the proteomic profiles of seminal plasma in rams [ 11 ] and Brangus bulls [ 12 ].…”