title: Early activation of sperm by HCO(3) (-) is regulated hormonally in the murine uterus.
abstract: Sperm deposited in the female genital tract receive signals for capacitation. Past work indicates that HCO(3) (-) is the initiating signal that the female reproductive tract contains the HCO(3) (-) -permeant anion channel cystic fibrosis transmembrane conductance regulator (CFTR) and that mutations in CFTR cause subfertility in both sexes. In this study, we examined whether CFTR controls uterine HCO(3) (-) content and sperm responses to it. Both CFTR protein and mRNA were absent in prepubertal murine uterus, but appeared in pubertal and adult tissues. Thus, CFTR is upregulated during development. Uterine CFTR mRNA additionally increased upon induced oestrus, most abundantly in uterus body and distal horns. Uterine fluid of oestrous females contained two-, and nearly fourfold more HCO(3) (-) than that of dioestrous and prepubertal animals, correlating with increased CFTR expression. For sperm incubated in and recovered from prepubertal uteri, flagellar beat frequency was no different from that before incubation. However, for sperm recovered from dioestrous and oestrous uteri, beat frequency was two- and fourfold higher, respectively. Thus, uterine HCO(3) (-) content may have physiological consequences for sperm motility. The male reproductive tract showed no regional distributions or developmental dependence of CFTR expression. Although the sperm flagellum showed CFTR immunoreactivity, CFTR blockers GlyH-101 or CFTR(inh) -172 did neither diminish HCO(3) (-) -evoked increases in sperm motility nor protein tyrosine phosphorylation. Our results indicate that in the uterus, both CFTR expression and the supply of HCO(3) (-) are upregulated hormonally. We propose that these changes coordinate ovulation with increases in sperm motility and promote other components of capacitation by pathways that do not require CFTR in sperm.
authors.affiliation: Department of Anatomy and Cell Biology, Saarland University, Homburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Mannowetz
authors.forename: P
authors.initials: P
authors.lastname: Wandernoth
authors.forename: J
authors.initials: J
authors.lastname: Hornung
authors.forename: U
authors.initials: U
authors.lastname: Ruffing
authors.forename: M
authors.initials: M
authors.lastname: Raubuch
authors.forename: G
authors.initials: G
authors.lastname: Wennemuth
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology*; D004971:Estrus; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D012741:Sexual Maturation; D013075:Sperm Capacitation / Q000187:drug effects; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology*; D053778:Thiazolidines / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000502:physiology*
chemical_list: C482900:3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone; D001565:Benzoates; D001639:Bicarbonates; D006834:Hydrazines; C548779:N-(2-naphthalenyl)-((3,5-dibromo-2,4-dihydroxyphenyl)methylene)glycine hydrazide; D012333:RNA, Messenger; D053778:Thiazolidines; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005998:Glycine