title: Sperm gamma-aminobutyric acid type A receptor delta subunit (GABRD) and its interaction with purinergic P2X2receptors in progesterone-induced acrosome reaction and male fertility.
abstract: The mechanism underlying the non-genomic action of progesterone in sperm functions and related Ca2+mobilisation remains elusive. Herein we report the expression of gamma-aminobutyric acid type A receptor delta subunit (GABRD) in human and rodent sperm and its involvement in mediating the progesterone-induced acrosome reaction. GABRD was localised in the sperm head/neck region. A δ(392-422)-specific inhibitory peptide against GABRD blocked the progesterone-induced acrosome reaction and the associated increase in intracellular Ca2+. Similarly, an inhibitory effect against both progesterone-induced Ca2+influx and the acrosome reaction was observed with a P2X2receptor antagonist. The lack of synergism between the GABRD and P2X2inhibitors suggests that these two receptors are playing a role in the same pathway. Furthermore, a co-immunoprecipitation experiment demonstrated that GABRD could undergo protein-protein interactions with the Ca2+-conducting P2X2receptor. This interaction between the receptors could be reduced following progesterone (10μM) inducement. Significantly reduced GABRD expression was observed in spermatozoa from infertile patients with reduced acrosome reaction capacity, suggesting that normal expression of GABRD is critical for the sperm acrosome reaction and thus male fertility. The results of the present study indicate that GABRD represents a novel progesterone receptor or modulator in spermatozoa that is responsible for the progesterone-induced Ca2+influx required for the acrosome reaction through its interaction with the P2X2receptor.
authors.affiliation: Joint Laboratory of Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, (Sichuan University), West China Second University Hospital, Sichuan University, Renmin Lanlu, 3 duan, No.17, Chengdu, 610041, PR China.
authors.forename: Wenming
authors.initials: W
authors.lastname: Xu
authors.affiliation: Joint Laboratory of Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, (Sichuan University), West China Second University Hospital, Sichuan University, Renmin Lanlu, 3 duan, No.17, Chengdu, 610041, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Joint Laboratory of Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, (Sichuan University), West China Second University Hospital, Sichuan University, Renmin Lanlu, 3 duan, No.17, Chengdu, 610041, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Joint Laboratory of Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, (Sichuan University), West China Second University Hospital, Sichuan University, Renmin Lanlu, 3 duan, No.17, Chengdu, 610041, PR China.
authors.forename: Xiao Tong
authors.initials: XT
authors.lastname: Liang
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Mei Kuen
authors.initials: MK
authors.lastname: Yu
authors.affiliation: Andrology clinic, Department of Obstetric and Gynecologic Diseases, West China Second University Hospital, Sichuan University, Chengdu, 610041, PR China.
authors.forename: Huanxun
authors.initials: H
authors.lastname: Yue
authors.affiliation: Membrane Physiology and Ion Channel Signalling Group, Division of Translational Bioscience, The John Curtin School of Medical Research, Building 54, Ward and Garran Roads, The Australian National University, Canberra, ACT 0200, Australia.
authors.forename: M Louise
authors.initials: ML
authors.lastname: Tierney
mesh_terms: D020101:Acrosome Reaction / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005298:Fertility / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism; D008297:Male; D051379:Mice; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D058476:Receptors, Purinergic P2X2 / Q000378:metabolism*; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D011963:Receptors, GABA-A; D058476:Receptors, Purinergic P2X2; D011374:Progesterone; D002118:Calcium