Repeated administration of prostaglandin F(2α) during the early luteal phase causes premature luteolysis in the pig

College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Biology of Reproduction (Impact Factor: 3.45). 08/1993; 49(1):181-5.
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ABSTRACT Previous investigators considered pig corpora lutea refractory to the luteolytic effects of prostaglandin (PG) F2 alpha before Day 12 of the estrous cycle. This study was designed to determine whether multiple injections of PGF2 alpha would result in a sustained reduction of serum progesterone and luteolysis, leading to significant shortening of the estrous cycle and interestrous interval. On Days 5-10 of an estrous cycle, gilts (n = 4) received injections of 12.5 mg PGF2 alpha (dinoprost tromethamine) i.m. every 12 h, or vehicle (PBS; n = 4) according to the same schedule. Mean interestrous interval in PGF2 alpha-treated gilts was reduced (p < 0.001) to 13.3 +/- 0.5 days compared with 19.8 +/- 0.6 days for control gilts. Serum progesterone declined below 1 ng/ml by Day 10.5 in PGF2 alpha-treated gilts compared to Day 17.5 in control animals. Serum concentrations of estradiol-17 beta (E2) reached maximal levels in PGF2 alpha-treated gilts earlier (Day 12.5) in the cycle than in control gilts (Day 19.5). Peak E2 and LH concentrations coincided with the periestrous period, suggesting that PGF2 alpha-induced estrus is accompanied by normal follicular development and ovulation. These results demonstrate that the pig is susceptible to the luteolytic effects of PGF2 alpha before Day 12 if repeated injections are given from Day 5 through Day 10.

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    • "Although porcine CL abundantly express PGF2a receptors (PTGFR) in the early luteal phase [1] [2], they remain insensitive to single treatment with exogenous PGF2a until Days 12 to 13 of the estrous cycle [3]. Interestingly , repeated injection of PGF2a on Day 5 of the estrous cycle induced luteolysis in pigs [4]. Nevertheless, there is still a lack of valuable explanation of mechanism responsible for resistance of porcine CL to treatment with exogenous PGF2a before Day 12 of the estrous cycle. "
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    ABSTRACT: The studies on the acquisition of luteolytic sensitivity have been focused mainly on molecular changes induced in the luteal tissue after treatment with exogenous PGF2α or on physiological changes occurring during the estrous cycle. The comparison of changes leading to the acquisition of luteolytic sensitivity after Day 12 of the estrous cycle and corresponding days of pregnancy has not been investigated in the pig. The present study was undertaken to evaluate (1) apoptosis measured as the proportions of early apoptotic, late apoptotic, and viable cells; (2) expression of factors involved in the extrinsic (TNFA/TNFα, TNFRSF1A/TNFR1, TNFRSF1B/TNFR2, FAS/Fas, and FASLG/FasL) and intrinsic (CASP3/Casp3, TP53/p-53, BAX/Bax, and BCL2/Bcl-2) apoptotic pathways, with two components of the activating protein-1 complex, i.e., FOS/Fos and JUN/Jun and IFNG/IFNγ; and (3) concentrations of luteal and blood plasma progesterone (P4) throughout the luteal phase of the estrous cycle and early pregnancy. Corpora lutea (CL) were collected postmortem on Days 8, 10, 12, and 14 of the estrous cycle and the corresponding days of pregnancy. The luteal tissue was subjected to RNA and/or protein isolation and disaggregation of CL cells followed by flow cytometry analysis aimed to determine apoptotic changes. Luteal and blood plasma P4 concentrations decreased on Day 14 of the estrous cycle versus pregnancy (P < 0.05 and P < 0.001, respectively). A significant increase in the number of early apoptotic cells and a decrease in the number of viable cells were observed on Day 14 of the estrous cycle (P < 0.001 and P < 0.05, respectively). Increase (P < 0.05) of TNFA messenger RNA (mRNA) level coincided with that of IFNG on Day 12 of the estrous cycle but not on the corresponding day of pregnancy. The content of FAS mRNA and protein increased on Day 14 of the estrous cycle versus pregnancy (P < 0.05). The mRNA expression of CASP3, BCL-2 and BAX was unchanged in cyclic and pregnant CL, while level of TP53 increased (P < 0.05) on Day 12 of the estrous cycle versus Day 8. The level of FOS and JUN mRNA increased (P < 0.05) on Day 14 of the estrous cycle versus the remaining days. The level of FOS and JUN mRNA was significantly higher (P < 0.001 and P < 0.05, respectively) on Day 14 of the estrous cycle than that on the corresponding day of pregnancy. In summary, the simultaneous increase of TNFA and IFNG transcript in cyclic CL suggests the crucial role of both cytokines in sensitization of porcine CL to further luteolytic action of PGF2α. The upregulated expression of FAS, FOS, and JUN mRNA in the late luteal phase in cyclic CL can indicate their involvement in structural luteolysis. The increased viability of luteal cells and elevated P4 concentrations in pregnant CL confirm the protective role of luteal P4 against apoptosis. Copyright © 2014 Elsevier Inc. All rights reserved.
    Theriogenology 10/2014; 83(4). DOI:10.1016/j.theriogenology.2014.10.016 · 1.85 Impact Factor
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    • "Therefore, CL resulting from hCG given on the day of farrowing could have been present for less than 12 d when PGF 2a was administered at weaning on d 14 of lactation. If this was the case, the dose used may not have been sufficient to stimulate complete regression (Estill et al., 1993); thus, weaning-to-estrus intervals similar to those in sows induced to ovulate but not receiving PGF 2a would be expected. However, it is difficult to explain why PGF 2a administered on d 14 of lactation would extend the resumption of normal reproductive activity of sows following weaning. "
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    ABSTRACT: Two experiments were conducted to examine the effectiveness of various strategies using gonadotropins to induce ovulation during lactation as a means of controlling the weaning-to-estrus interval in sows. The objective of Exp. 1 was to examine the efficacy of various gonadotropin regimens for induction of ovulation during lactation. Primiparous (n = 60) and multiparous (n = 83) crossbred sows were assigned, before farrowing, to one of four treatments: no injection (control); 1,000 IU hCG on d 0 (hCG-0; d 0 = day of farrowing); P.G. 600 + 1,000 IU hCG 4 and 7 d after farrowing, respectively (hCG-7); or P.G. 600 + 1,000 IU hCG 11 and 14 d after farrowing, respectively (hCG-14). Sows were weaned on 18 +/- 2 d after farrowing and monitored daily for estrus via exposure to mature boars. The criterion for determining the induction of ovulation was a sustained increase in serum progesterone concentrations above 4.0 ng/mL. The most consistent response to exogenous gonadotropins was on d 0, with an 80% response in primiparous sows (12/15) and a 71% response in multiparous sows (15/21). Weaning-to-estrus intervals for multiparous sows were longer (P = .05) for hCG-14 and hCG-7 than for control and hCG-0 sows. Weaning-to-estrus intervals for primiparous sows were longer (P = .05) for the hCG-14 than for the hCG-0 treatment. The objective of Exp. 2 was to ascertain the effects of postpartum treatment with hCG (1,000 IU) on d 0 and PGF2alpha (10 mg) at d 14 on the weaning-to-estrus interval in multiparous sows weaned at d 14 after birth. Before farrowing, sows (n = 60) were randomly assigned to one of four treatments: positive control, weaning at d 21; negative control, weaning at d 14; hCG within 24 h after farrowing, weaning at d 14; or hCG within 24 h after farrowing and PGF2alpha at weaning, weaning at d 14. Weaning-to-estrus intervals were longer (P = .05) in sows receiving PGF2alpha than in the other treatments. Results indicate that it is possible to induce ovulation immediately after farrowing, using a single injection of hCG, and this strategy can be used to uncouple weaning from the resumption of reproductive activity. However, the administration of PGF2alpha at 14 d after farrowing did not consistently cause regression of the induced corpora lutea.
    Journal of Animal Science 10/1999; 77(9):2533-9. · 1.92 Impact Factor
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    • "The tenet that OT promoted uterine PGF 2a release and caused a relatively small decrease in mean IEI is consistent with the luteolytic effect of exogenous PGF 2a , which reduced IEI when given after d 12 in gilts (Diehl and Day, 1974; Hallford et al., 1975; Douglas and Ginther, 1975; Guthrie and Polge, 1976). This is probably due to the nature of pig CL, which are generally unresponsive to PGF 2a until after d 12 (Guthrie and Polge, 1976; Moeljono et al., 1976), although Estill et al. (1993) reported that twice-daily injections of PGF 2a on d 5 through 10 decreased IEI by 6 d. However, the physiological significance of this latter finding is unclear because endogenous PGF 2a secretion does not increase until d 10 to 12 in pigs. "
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    ABSTRACT: Oxytocin (OT) stimulates pulsatile secretion of uterine PGF2 alpha in ruminants, but the role of OT in regulation of the estrous cycle of pigs is not clear. four experiments were performed to examine the effect of exogenous OT on interestrous interval of intact cyclic and hysterectomized gilts. In Exp. 1, i.v. injections of 20 USP units (equivalent to 20 IU) of OT, once/day via an ear vein on d 10, 12, 14, and 16 after estrus, decreased (P < .01) interestrous interval (19.9 +/- .2 d) compared with vehicle-injected control gilts (20.8 +/- .2 d), without affecting ovulation rate (12.1 vs. 12.0 +/- .7 corpora lutea; OT vs control gilts) at subsequent estrus. In Exp. 2, i.v. infusions of 20 USP units of OT, twice/day via an indwelling jugular catheter on d 10 to 16 after estrus, did not alter interestrous interval (20.6 +/- .3 d) compared with control gilts (20.4 +/- .3 d). Concentrations of progesterone in jugular vein plasma did not differ between treatment groups on d 9 to 21 after estrus. In Exp. 3, i.m. injections of 20 USP units of OT, twice/day on d 10 to 16 after estrus, decreased (P < .05) interestrous interval (20.6 +/- .4 d) compared with control gilts (22.3 +/- .4 d). In Exp. 4, i.m. injections of 20 USP units of OT, twice/day on d 10 to 16 after estrus, decreased (P < .05) interestrous interval (20.7 +/- .3 d) compared with control injections in uterine-intact gilts (21.8 +/- .3 d). None of the gilts hysterectomized on d 7 and treated on d 10 to 16 after estrus with either OT or control injections returned to estrus by d 28, and all had increased plasma progesterone on d 21 to 27. Mean weight of individual corpora lutea (502 vs 449 +/- 28 mg; OT vs control gilts) and total weight of corpora lutea (5,758 vs. 5,126 +/- 298 mg; OT vs control gilts) of hysterectomized gilts did not differ between treatment groups at ovariectomy on d 28. These results indicate that 1) exogenous OT administered on d 10 to 16 shortened the interestrous interval of intact cyclic gilts and 2) the effect of OT was uterine-dependent.
    Journal of Animal Science 12/1995; 73(12):3681-6. · 1.92 Impact Factor
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