Abstract
BackgroundThrough this prospective study, we aimed to explore the change of molecular modification after the transient scrotal hyperthermia on human sperm.MethodsTen 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.ResultsIn 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.ConclusionsThe 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.
Highlights
In mammals, including humans, the scrotal temperature required for normal spermatogenesis within the testes is 2 °C to 8 °C lower than the core body temperature
Many studies have evaluated the effect of scrotal hyperthermia, the molecular change underlying the oligospermia or asthenospermia induced by heat stress remains unclear
Functional characterization and annotation of the differentially expressed proteins To define fold change values that reflect the effect of scrotal hyperthermia on human sperm, the ratios of sperm proteins 2 weeks before and 6 weeks after scrotal hyperthermia in two independent biological duplicate groups were determined by protein labeling with isobaric tags 114/113 and 116/115
Summary
In mammals, including humans, the scrotal temperature required for normal spermatogenesis within the testes is 2 °C to 8 °C lower than the core body temperature. Exposing the testes of mice [4], rats [5, 6], monkeys [7], bulls [8], sheep [9], and humans [10, 11] to high temperatures induced germ cell apoptosis in spermatogenesis [12]. Many studies have evaluated the effect of scrotal hyperthermia, the molecular change underlying the oligospermia or asthenospermia induced by heat stress remains unclear. Through this prospective study, we aimed to explore the change of molecular modification after the transient scrotal hyperthermia on human sperm
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