Zona pellucida-induced acrosome reaction in human spermatozoa is potentiated by glycodelin-A via down-regulation of extracellular signal-regulated kinases and up-regulation of zona pellucida-induced calcium influx

被引：19

作者：

Chiu, Philip C. N. ^{[1
,2
]}

Wong, Ben S. T. ^{[1
]}

Lee, Cheuk-Lun ^{[1
]}

Lam, Kevin K. W. ^{[1
]}

Chung, Man-Kin ^{[3
]}

Lee, Kai-Fai ^{[1
,2
]}

Koistinen, Riitta ^{[4
]}

Koistinen, Hannu ^{[4
]}

Gupta, Satish K. ^{[5
]}

Seppala, Markku ^{[4
]}

Yeung, William S. B. ^{[1
,2
]}

机构：

[1] Univ Hong Kong, Dept Obstet & Gynaecol, Hong Kong, Hong Kong, Peoples R China

[2] Univ Hong Kong, Ctr Reprod Dev & Growth, Hong Kong, Hong Kong, Peoples R China

[3] Chinese Univ Hong Kong, Queen Mary Hosp, Fac Med, Dept Obstet & Gynaecol, Hong Kong, Hong Kong, Peoples R China

[4] Univ Helsinki, Cent Hosp, Hus Helsinki 00029, Finland

[5] Natl Inst Immunol, Reprod Cell Biol Lab, New Delhi 110067, India

来源：

HUMAN REPRODUCTION | 2010年 / 25卷 / 11期

基金：

芬兰科学院;

关键词：

glycodelin; zona pellucida; sperm acrosome reaction; ERK; intracellular calcium; ACTIVATED PROTEIN-KINASE; CAPACITATING HUMAN SPERMATOZOA; RAS-DEPENDENT ACTIVATION; HUMAN SPERM CAPACITATION; HUMAN FOLLICULAR-FLUID; INHIBITORY FACTOR-I; PLACENTAL PROTEIN-14; MAP KINASE; TYROSINE PHOSPHORYLATION; B-RAF;

D O I：

10.1093/humrep/deq243

中图分类号：

R71 [妇产科学];

学科分类号：

100211 ;

摘要：

Glycodelin-A interacts with spermatozoa before fertilization, but its role in modulating sperm functions is not known. Zona pellucida-induced acrosome reaction is crucial to fertilization and its dysfunction is a cause of male infertility. We hypothesized that glycodelin-A, a glycoprotein found in the female reproductive tract, potentiates human spermatozoa for zona pellucida-induced acrosome reaction. Glycodelin isoforms were immunoaffinity purified. The sperm intracellular cAMP concentration, protein kinase-A (PKA) and extracellular signal-regulated kinase (ERK) activities, and intracellular calcium were measured by ELISA, kinase activity assay kits and Fluo-4AM technique, respectively. The phosphorylation of inositol 1,4,5-trisphosphate type-1 receptor (IP3R1) mediated by ERK was determined by western blotting. Zona pellucida-induced acrosome reaction was detected by Pisum sativum staining. Pretreatment of spermatozoa with glycodelin-A significantly up-regulated adenylyl cyclase/PKA activity and down-regulated the activity of ERK and its phosphorylation of IP3R1, thereby enhancing zona pellucida-induced calcium influx and zona pellucida-induced acrosome reaction. Glycodelin-F or deglycosylated glycodelin-A did not have these actions. Treatment of spermatozoa with a protein kinase inhibitor abolished the priming activity of glycodelin-A, whilst ERK pathway inhibitors mimic the stimulatory effect of glycodelin-A on zona pellucida-induced acrosome reaction. Glycodelin-A in the female reproductive tract sensitizes spermatozoa for zona pellucida-induced acrosome reaction in a glycosylation-specific manner through activation of the adenylyl cyclase/PKA pathway, suppression of extracellular signal-regulated kinase activation and up-regulation of zona pellucida-induced calcium influx. The action of glycodelin-A may be important in vivo to ensure full responsiveness of human spermatozoa to the zona pellucida.

引用

页码：2721 / 2733

页数：13

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