Induction of parturition in the bitch with the progesterone-receptor blocker aglépristone

Baan, Mieke; Taverne, M.A.M.; Kooistra, H.S.; Gier, J. De; Dieleman, S.J.; Okkens, A.C.

doi:10.1016/j.theriogenology.2004.09.008

Cited by 52 publications

(79 citation statements)

References 26 publications

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“…Although the mean gestational length in beef cattle used by Li et al (1991) and Dlamini et al (1995) was slightly longer than in Holstein cows used in our study (beef cows: 286G2.3 days; beef heifers: 284G1.5 days; Holstein: 280.5G1.3 days), uterine activation by upregulating a cassette of contraction-associated proteins and/or the conditioning of the systems providing uterotonins such as oxytocin and PGF 2a (Whittle et al 2001) -presumably by signals from the fetal side -may have been substantially different at the onset of antiprogestin treatment between the two experimental settings. A similar situation has been postulated for the dog, where, depending on the time of antiprogestin treatment, parturition with impaired or efficient (Baan et al 2005) expulsion of the puppies had been observed. The assumption that in our study antiprogestin treatment was started at an earlier stage of readiness for parturition compared with the study by Li et al (1991) and Dlamini et al (1995) is also substantiated by the observation that in our experiment calves from Ap-treated animals and from day 272 controls were viable but needed considerable clinical care during the first week after Figure 4 Concentrations of progesterone, estradiol 17b, estrone, and estrone sulfate in four untreated control cows during late gestation and around normal term.…”

Section: Discussionsupporting

confidence: 63%

Use of the progesterone (P4) receptor antagonist aglepristone to characterize the role of P4 withdrawal for parturition and placental release in cows

Shenavai¹,

Hoffmann²,

Dilly³

et al. 2010

Reproduction

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In late pregnant cows, progesterone (P 4 ) is mainly of luteal origin. However, the trophoblast may provide high local P 4 concentrations in the uterus. To test for the importance of a complete P 4 withdrawal for parturition-related processes and placental release, the P 4 receptor (PGR) blocker aglepristone (Ap) was administered to three cows on days 270 and 271 of pregnancy. A complete opening of the cervix was observed 46.5G7.3 h after the start of treatment. However, expulsion of the calves was impaired obviously because of insufficient myometrial activity, and placental membranes were retained for at least 10 days. Measurement of P 4 concentrations indicated that PGR blockage induced luteolysis. To investigate the role of P 4 withdrawal for the prepartal tissue remodeling of the placentomes, the caruncular epithelium was evaluated by morphometry, and the percentage of trophoblast giant cells (TGCs) relative to the total number of trophoblast cells were assessed. Caruncular epithelium in Ap-treated cows (D272CAp) was immature (30.5G3.3%) and not different from untreated controls (elected cesarean section (CS) on day 272; D272-CS; 31.5G1.4%), whereas it was significantly reduced at normal term (D280.5G1.3; 21.0G6.1%; PZ0.011). Correspondingly, the percentage of TGCs were 20.1G1.4 in D272CAp, 22.1G4.8 in D272-CS, and 9.8G3.9 at term (PZ0.001). No effect was detected on placental estrogen synthesis. The results showed that in late pregnant cows, P 4 withdrawal only induces a limited spectrum of the processes related to normal parturition and is not a crucial factor for the prepartal tissue remodeling in placentomes and the timely release of the placenta.

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Section: Discussionsupporting

confidence: 63%

Use of the progesterone (P4) receptor antagonist aglepristone to characterize the role of P4 withdrawal for parturition and placental release in cows

Shenavai¹,

Hoffmann²,

Dilly³

et al. 2010

Reproduction

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“…Our results also provide an explanation of the observation that aglepristone-induced parturition in the dog may require or may not require ecbolic support (Hoffmann et al 1999, Baan et al 2005. As provision of adequate amounts of PTGS2 seems to be restricted to the immediate phase prior to parturition, the time point of treatment with the antiprogestin seems to be the critical issue.…”

Section: Discussionmentioning

confidence: 54%

Canine placenta: a source of prepartal prostaglandins during normal and antiprogestin-induced parturition

et al. 2010

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Expression of cyclooxygenase 2 (COX2, now known as PTGS2), prostaglandin E2 synthase (PTGES, PGES), and prostaglandin F2a synthase (PGFS), of the respective receptors PTGFR (FP), PTGER2 (EP2), and PTGER4 (EP4) and of the progesterone receptor (PGR, PR) was assessed by real-time PCR, immunohistochemistry (IHC), or in situ hybridization (ISH) in utero/placental tissue samples collected from three to five bitches on days 8-12 (pre-implantation), 18-25 (post-implantation), and 35-40 (mid-gestation) of pregnancy and during the prepartal luteolysis. Additionally, ten mid-pregnant bitches were treated with the antiprogestin aglepristone (10 mg/kg bw (2!/24 h)); ovariohysterectomy was 24 and 72 h after the second treatment. Plasma progesterone and 15-ketodihydro-PGF2a (PGFM) concentrations were determined by RIA. Expression of the PGR was highest before implantation and primarily located to the endometrium; expression in the placenta was restricted to the decidual cells. PTGS2 was constantly low expressed until mid-gestation; a strong upregulation occurred at prepartal luteolysis concomitant with an increase in PGFM. PGFS was upregulated after implantation and significantly elevated through early and mid-gestation. PTGES showed a gradual increase and a strong prepartal upregulation. PTGFR, PTGER2, and PTGER4 were downregulated after implantation; a gradual upregulation of PTGFR and PTGER2 occurred towards parturition. ISH and IHC co-localized PGFS, PTGFR, PTGES, and PTGS2 in the trophoblast and endometrium. The changes following application of aglepristone were in the same direction as those observed from mid-gestation to prepartal luteolysis. These data suggest that the prepartal increase of PGF2a results from a strong upregulation of PTGS2 in the fetal trophoblast with the withdrawal of progesterone having a signalling function and the decidual cells playing a key role in the underlying cell-to-cell crosstalk.

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“…Blood samples for determination of the plasma concentrations of GH and IGF-I were collected before MPA treatment, at days À9, À8, À7, À5, À3, À2, À1, and 0 (=immediately before aglépristone treatment and after MPA treatment for over 1 year), at days 1, 3,5,7,8,11,13,15,18,20,22, and 25 (=during aglépristone treatment), and at days 46 and 60 (=3.5 and 5.5 weeks after the last aglépristone treatment). On days of treatment (MPA or aglépristone), blood samples were collected prior to the drug administration.…”

Section: Blood Sample Collectionmentioning

confidence: 99%

“…Aglépristone is the first progesterone receptor blocker licensed for veterinary use and has been used efficiently to terminate pregnancy [16,17] and to induce parturition [18]. Furthermore, it is successfully used for the treatment of fibroadenomatous mammary hyperplasia in cats [19][20][21] and may be a useful adjunct in the medical treatment of endometritis and pyometra in the dog [22].…”

Section: Introductionmentioning

confidence: 99%

Treatment of growth hormone excess in dogs with the progesterone receptor antagonist aglépristone

et al. 2006

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Acromegaly or hypersomatotropism in dogs is almost always due to progestin-induced hypersecretion of GH originating from the mammary gland. The aim of this study was to investigate whether aglépristone, a progesterone receptor antagonist, can be used to treat this form of canine acromegaly. In five Beagle bitches hypersomatotropism was induced by administration of MPA for over 1 year. Subsequently, aglépristone was administered. Blood samples were collected before MPA administration, immediately before, during, and 3.5 and 5.5 weeks after the last administration of aglépristone for determination of the plasma concentrations of GH and IGF-I. In addition, blood samples for the determination of the 6-h plasma profile of GH were collected before MPA administration, before aglépristone administration, and 1 week after the last aglépristone treatment.MPA administration resulted in a significant increase of the mean plasma IGF-I concentration, whereas analysis of the pulsatile plasma profile demonstrated a trend (P = 0.06) for a higher mean basal plasma GH concentration and a higher mean AUC 0 for GH. Treatment with aglépristone resulted in a significant decrease of the mean plasma GH and IGF-I concentrations. Analysis of the pulsatile plasma profile showed a trend (P = 0.06) for a lower mean basal plasma GH concentration and a lower mean AUC 0 for GH 1 week after the last aglépristone treatment compared with these values before aglépristone administration. Three and a half and 5.5 weeks after the last aglépristone administration the mean plasma IGF-I concentration increased again.In conclusion, aglépristone can be used successfully to treat dogs with progestin-induced hypersomatotropism. #

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Induction of parturition in the bitch with the progesterone-receptor blocker aglépristone

Cited by 52 publications

References 26 publications

Use of the progesterone (P4) receptor antagonist aglepristone to characterize the role of P4 withdrawal for parturition and placental release in cows

Use of the progesterone (P4) receptor antagonist aglepristone to characterize the role of P4 withdrawal for parturition and placental release in cows

Canine placenta: a source of prepartal prostaglandins during normal and antiprogestin-induced parturition

Treatment of growth hormone excess in dogs with the progesterone receptor antagonist aglépristone

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