Progesterone requires heat shock protein 90 (HSP90) in human sperm to regulate motility and acrosome reaction
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The aims of this paper were to study whether heat shock protein 90 (HSP90) is a regulator of sperm functions and to determine its association with oligoasthenozoospermia.
The levels of HSP90 in sperm lysates were measured by ELISA. Localization of HSP90 and its isoforms was evaluated by immunofluorescence. Sperm motility and kinetics were assessed by computer-assisted sperm analysis. Acrosome reaction was determined by lectin staining.
The levels of HSP90 were lower in oligoasthenozoospermic men and correlated positively with the number of motile spermatozoa. In capacitated human spermatozoa, HSP90α was mostly found in residual nuclear envelope, and the HSP90β isoform was higher in the flagella. Inhibition of HSP90 by geldanamycin or 17-AAG did not affect basal motility, but suppressed progesterone-mediated forward progressive motility, hyperactivation and acrosome reaction. Progesterone treatment dephosphorylated both HSP90α and HSP90β at Ser/Thr-Pro residues, but not Tyr residues.
HSP90 levels are downregulated in oligoasthenozoospermia, and its functional inhibition attenuates progesterone-mediated sperm motility and acrosome reaction.
KeywordsHeat shock protein HSP90 Human sperm Motility Acrosome reaction Progesterone Oligoasthenozoospermia Phosphorylation
We are grateful to Dr. A S Sreedhar (Scientist, Centre for Cellular and Molecular Biology, Hyderabad, India) for generously sparing the geldanamycin and 17-AAG used in this study. The study (RA/382/06-2016) is funded by grants from the Department of Biotechnology, Innovative Young Biotechnologist Award (IYBA) and Indian Council of Medical Research (ICMR), Government of India, New Delhi, India. VSP is a recipient of a Senior Research Fellowship from ICMR. DM is a recipient of the IYBA grant.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
Indian Council of Medical Research, Department of Biotechnology, Government of India
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