title: Progesterone requires heat shock protein 90 (HSP90) in human sperm to regulate motility and acrosome reaction.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  HSP90 levels are downregulated in oligoasthenozoospermia, and its functional inhibition attenuates progesterone-mediated sperm motility and acrosome reaction.
authors.affiliation: Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive Health (ICMR), J. M. Street, Parel, Mumbai, 400012, India.
authors.forename: Vrushali
authors.initials: V
authors.lastname: Sagare-Patil
authors.affiliation: Hinduja IVF Centre, PD Hinduja Hospital and Medical Research Center, Veer Savarkar Marg, Mahim, Mumbai, 400016, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Bhilawadikar
authors.affiliation: Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive Health (ICMR), J. M. Street, Parel, Mumbai, 400012, India.
authors.forename: Mosami
authors.initials: M
authors.lastname: Galvankar
authors.affiliation: Hinduja IVF Centre, PD Hinduja Hospital and Medical Research Center, Veer Savarkar Marg, Mahim, Mumbai, 400016, India.
authors.forename: Kusum
authors.initials: K
authors.lastname: Zaveri
authors.affiliation: Hinduja IVF Centre, PD Hinduja Hospital and Medical Research Center, Veer Savarkar Marg, Mahim, Mumbai, 400016, India.
authors.forename: Indira
authors.initials: I
authors.lastname: Hinduja
authors.affiliation: Molecular and Cellular Biology Laboratory, National Institute for Research in Reproductive Health (ICMR), J. M. Street, Parel, Mumbai, 400012, India. deepaknmodi@yahoo.com.
authors.forename: Deepak
authors.identifier: http://orcid.org/0000-0002-4230-4219
authors.initials: D
authors.lastname: Modi
mesh_terms: D020101:Acrosome Reaction / Q000235:genetics; D016227:Benzoquinones / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D008297:Male; D009845:Oligospermia / Q000235:genetics* / Q000503:physiopathology; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D055101:Semen Analysis; D013075:Sperm Capacitation / Q000235:genetics; D013081:Sperm Motility / Q000187:drug effects / Q000235:genetics; D013094:Spermatozoa / Q000254:growth & development* / Q000473:pathology
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D011374:Progesterone; C112765:tanespimycin; C001277:geldanamycin
keywords: Acrosome reaction; HSP90; Heat shock protein; Human sperm; Motility; Oligoasthenozoospermia; Phosphorylation; Progesterone