title: Gradients of natriuretic peptide precursor A (NPPA) in oviduct and of natriuretic peptide receptor 1 (NPR1) in spermatozoon are involved in mouse sperm chemotaxis and fertilization.
abstract: Selective spermatozoa movement from storage of the oviduct to fertilization site is suggested to be a result of chemotaxis. In the present study, Natriuretic peptide precursor A (NPPA) induced sperm chemotaxis in capillaries and enhanced intracellular Ca(2+) level, both of which could be blocked by the Natriuretic Peptide Receptor 1 (NPR1) inhibitor anantin and the cGMP-dependent protein kinase (PKG) inhibitors, KT5823 and Rp-8-Br-PET-cGMPS. NPPA also increased spermatozoa kinetic parameters of VAP, VSL, LIN, STR, and BCF. Only 2.0% of positive staining for NPR1 was detected in fresh spermatozoa. The positive rate was increased in capacitated spermatozoa (20.5%), and further increased in spermatozoa of NPPA treatment (70.2%). Nppa mRNA level in the ampullae was significantly higher compared with that in isthmus and uterotubal junction, and NPPA protein had an ascending gradient (AG) from the uterotubal junction to ampullae in gonadotropin-treated mice. NPPA induced sperm chemotaxis in diestrus oviducts without a NPPA gradient, and sperm chemotaxis occurred in the oviducts of gonadotropin-treated mice. These effects were inhibited by anantin. Meanwhile, sperm chemotaxis also occurred in unilateral ovariectomized oviducts of gonadotropin-treated mice, in which the possible effect of follicular fluid and oocyte-cumulus mass were eliminated when ovulation occurs. Furthermore, anantin significantly decreased the rate of fertilization in a dose-dependent manner (0.1 µM, 57.1%; 1 µM, 33.8%) compared with control (78.5%). These results suggest that a NPPA gradient originating in the oviduct induces sperm chemotaxis by binding to its receptor NPR1 and then activating PKG pathway, and plays a physiological role in fertilization.
authors.affiliation: State Key Laboratory of Agro-biotechnology, College of Biological Science, China Agricultural University, Beijing, PR China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Bian
authors.forename: Guankun
authors.initials: G
authors.lastname: Mao
authors.forename: Meng
authors.initials: M
authors.lastname: Guo
authors.forename: Guanping
authors.initials: G
authors.lastname: Mao
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
authors.forename: Junxia
authors.initials: J
authors.lastname: Li
authors.forename: Yingying
authors.initials: Y
authors.lastname: Han
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Chen
authors.forename: Meijia
authors.initials: M
authors.lastname: Zhang
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xia
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor; D002118:Calcium / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D005260:Female; D005306:Fertilization / Q000187:drug effects*; D006062:Gonadotropins / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology*; D010057:Oviducts / Q000166:cytology / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology*; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
chemical_list: D006062:Gonadotropins; C431578:Nppa protein, mouse; D010456:Peptides, Cyclic; D011498:Protein Precursors; D020098:Natriuretic Peptide, C-Type; C068090:anantin; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D002118:Calcium