title: Effects of exogenous recombinant ovine interferon tau on circulating concentrations of progesterone, cortisol, luteinizing hormone, and antiviral activity; interestrous interval; rectal temperature; and uterine response to oxytocin in cyclic ewes.
abstract: Interferon tau (IFN tau) is the conceptus-produced antiluteolytic signal in ruminants. Three experiments examined the effects of s.c. administration of recombinant ovine (ro)IFN tau on interestrous interval (IEI), oxytocin (OT)-induced uterine prostaglandin F2alpha metabolite (PGFM) production, rectal temperature (RT), respiration rate (RR), and plasma concentrations of progesterone, cortisol, LH, and antiviral activity (AVA) in plasma and uterine flushings. In experiment I, 20 ewes were treated s.c. with either 0, 1, 2, or 4 mg/day roIFN tau (0.7 x 10(8) U/mg; 5 ewes/dosage) from Days 11 to 15 of the estrous cycle (estrus = Day 0) and were challenged with OT (30 IU) on Day 15. Jugular blood samples were collected at -10, 0, 10, 20, 30, 40, 50, and 60 min relative to the OT challenge and assayed for PGFM. Recombinant oIFN tau increased IEI (16.7, 18.7, and 22.6 +/- 0.6 days for 0, 2, and 4 mg roIFN tau, respectively, p < 0.01). Recombinant oIFN tau did not affect peak PGFM response to OT (2309 +/- 172 pg/ml; p > 0.1). However, the 4 mg/day dosage delayed the time to peak PGFM (32.4 vs. 47.5 +/- 3.4 min; p < 0.01, 0 vs. 4 mg) and resulted in approximately 200% higher concentrations of PGFM at 60 min post-OT (0 vs. 4 mg/day, p < 0.07). Experiment II was similar to experiment I, except that only the 0- and 4-mg/day dosages of roIFN tau were administered. Ewes were hysterectomized on Day 16, and assay of uterine flushes detected no AVA from ewes treated with either 0 or 4 mg/day roIFN tau. In experiment III, 20 ewes were treated s.c. with either 0, 2, 4, or 6 mg roIFN tau on Day 12. Blood samples, RT, and RR were obtained at frequent intervals for 24 h, and plasma was assayed for progesterone, cortisol, LH, and AVA. Plasma AVA, which increased in a dose-dependent manner, was detectable within 60 min and remained elevated at 24 h compared to control values. RT (elevated 0.5-1.0 degrees C), RR, and cortisol increased in response to all dosages of roIFN tau, with peak values occurring 150-180 min postinjection. For all dosages of roIFN tau, plasma progesterone declined from 120 to 360 min posttreatment and then returned to pretreatment values by 24 h (p < 0.01) as compared to controls. Overall, exogenous roIFN tau altered uterine PGFM response to OT from a pulse to a gradual and sustained elevation and extended IEI with only a transient decline in progesterone and mild hyperthermia, effects that are not expected to compromise pregnancy.
authors.affiliation: Department of Animal Science, Center for Animal Biotechnology, Institute of Biosciences and Technology, Texas A&M University, College Station 77843-2471, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Ott
authors.forename: J G
authors.initials: JG
authors.lastname: Fleming
authors.forename: T E
authors.initials: TE
authors.lastname: Spencer
authors.forename: M M
authors.initials: MM
authors.lastname: Joyce
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.forename: C N
authors.initials: CN
authors.lastname: Green
authors.forename: D
authors.initials: D
authors.lastname: Zhu
authors.forename: T H
authors.initials: TH
authors.lastname: Welsh
authors.forename: P G
authors.initials: PG
authors.lastname: Harms
authors.forename: F W
authors.initials: FW
authors.lastname: Bazer
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000097:blood; D001831:Body Temperature / Q000187:drug effects; D015237:Dinoprost / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004971:Estrus / Q000187:drug effects*; D005260:Female; D005298:Fertility / Q000187:drug effects; D006728:Hormones / Q000097:blood*; D006854:Hydrocortisone / Q000097:blood; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007986:Luteinizing Hormone / Q000097:blood; D010121:Oxytocin / Q000494:pharmacology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D011374:Progesterone / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D012756:Sheep; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D006728:Hormones; D007370:Interferon Type I; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; C020947:interferon tau; D011374:Progesterone; D010121:Oxytocin; D007986:Luteinizing Hormone; D015237:Dinoprost; D006854:Hydrocortisone