title: Mares with delayed uterine clearance have an intrinsic defect in myometrial function.
abstract: Persistent, postmating endometritis affects approximately 15% of mares and results in reduced fertility and sizable economic losses to the horse-breeding industry. Mares that are susceptible to postmating endometritis have delayed uterine clearance associated with reduced uterine contractility. Unfortunately, the mechanism for reduced uterine contractility remains an enigma. The present study examined the hypothesis that mares with delayed uterine clearance have an intrinsic contractile defect of the myometrium. Myometrial contractility was evaluated in vitro by measuring isometric tension generated by longitudinal and circular uterine muscle strips in response to KCl, oxytocin, and prostaglandin F(2alpha) (PGF(2alpha)) for young nulliparous mares, older reproductively normal mares, and older mares with delayed uterine clearance. In addition, intracellular Ca(2+) regulation was evaluated using laser cytometry to measure oxytocin-stimulated intracellular Ca(2+) transients of myometrial cells loaded with a Ca(2+)-sensitive fluorescent dye, fluo-4. For all contractile agonists, myometrium from mares with delayed uterine clearance failed to generate as much tension as myometrium from older normal mares. Oxytocin-stimulated intracellular Ca(2+) transients were similar for myometrial cells from mares with delayed uterine clearance and from older normal mares, suggesting that the contractile defect did not result from altered regulation of intracellular Ca(2+) concentration. Furthermore, no apparent age-dependent decline was observed in myometrial contractility; KCl-depolarized and oxytocin-stimulated longitudinal myometrium from young normal mares and older normal mares generated similar responses. However, circular myometrium from young normal mares failed to generate as much tension as myometrium from older normal mares when stimulated with oxytocin or PGF(2alpha), suggesting possible age-related alterations in receptor-second messenger signaling mechanisms downstream of intracellular Ca(2+) release. In summary, for mares with delayed uterine clearance, an intrinsic contractile defect of the myometrium may contribute to reduced uterine contractility following breeding.
authors.affiliation: Department of Large Animal Medicine & Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4475, USA. srigby@cvm.tamu.edu
authors.forename: S L
authors.initials: SL
authors.lastname: Rigby
authors.forename: R
authors.initials: R
authors.lastname: Barhoumi
authors.forename: R C
authors.initials: RC
authors.lastname: Burghardt
authors.forename: P
authors.initials: P
authors.lastname: Colleran
authors.forename: J A
authors.initials: JA
authors.lastname: Thompson
authors.forename: D D
authors.initials: DD
authors.lastname: Varner
authors.forename: T L
authors.initials: TL
authors.lastname: Blanchard
authors.forename: S P
authors.initials: SP
authors.lastname: Brinsko
authors.forename: T
authors.initials: T
authors.lastname: Taylor
authors.forename: M K
authors.initials: MK
authors.lastname: Wilkerson
authors.forename: M D
authors.initials: MD
authors.lastname: Delp
mesh_terms: D000814:Aniline Compounds; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004716:Endometritis / Q000503:physiopathology / Q000662:veterinary*; D005260:Female; D005456:Fluorescent Dyes; D006734:Horse Diseases / Q000503:physiopathology*; D006736:Horses; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000503:physiopathology; D009215:Myometrium / Q000503:physiopathology*; D010121:Oxytocin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000503:physiopathology*; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; C409648:Fluo 4; D005456:Fluorescent Dyes; D014966:Xanthenes; D010121:Oxytocin; D011189:Potassium Chloride; D015237:Dinoprost; D002118:Calcium