Inhibition of egg development and implantation in rats after post-coital administration of the progesterone antagonist RU 486

Psychoyos, A; Prapas, Ioannis

doi:10.1530/jrf.0.0800487

Cited by 64 publications

(30 citation statements)

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“…It has been reported that postcoital administration of mifepristone modulates egg transport through the oviduct (Roblero, et al, 1987;Fuentealba, et al, 1987;Yang and Wu, 1990), retards early embryonic development (Psychoyos and Prapas, 1987;Roblero and Croxatto, 1991), delays endometrial maturation (Roblero and Croxatto, 1991;Batista, et al, 1992;Cameron, et al, 1996) and thereby inhibits or delays implantation (Psychoyos and Prapas, 1987;Roblero and Croxatto, 1991;Dao, et al, 1996). In the present study, treatment with 4 mg/kg mifepristone during the post-coital phase produced small numbers of live embryos and a high postimplantation embryonic mortality but did not reduce the number of implantations.…”

Section: Discussioncontrasting

confidence: 51%

Collaborative work on evaluation of ovarian toxicity 2) Two- or four-week repeated dose studies and fertility study of mifepristone in female rats

et al. 2009

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-In order to assess ovarian pathological changes and their relationship to changes in female fertility parameters, mifepristone, a progesterone receptor antagonist, was selected as the test article and was administered orally to female rats at dose levels of 0, 0.8, 4, 20 and 100 mg/kg for 2 or 4 weeks in repeated dose-toxicity studies and in a female fertility study at dose levels of 0, 0.8, 4 and 20 mg/kg from > 2 weeks before copulation to postcoital day 7. In the repeated dose toxicity studies, persistent estrus was seen in the vaginal smears, and multiple cysts in the ovaries at necropsy, increases in luteinized cysts and hypertrophy of previously formed corpora lutea were observed in the histopathological examination of ovaries in rats receiving 20 mg/kg or more for 2 or 4 weeks. In female fertility studies, persistent vaginal the animals were completely infertile when dosed with 20 mg/kg during the post-coital period. An increase in pre-implantation losses was observed in the animals treated with 20 mg/kg during the pre-coital phase, while treatment with 4 mg/kg mifepristone during the post-coital phase induced an increase in post-implan-

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Section: Discussioncontrasting

confidence: 51%

Collaborative work on evaluation of ovarian toxicity 2) Two- or four-week repeated dose studies and fertility study of mifepristone in female rats

et al. 2009

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“…We have earlier reported that monkey embryos exposed in vivo to mifepristone fail to yield evolutive implantation (Ghosh et al 1997). Psychoyos & Prapas (1987) observed that administration of mifepristone to rats on days 1 and 2 of pregnancy resulted in a blockade of the morula-to-blastocyst transition.…”

Section: Discussionmentioning

confidence: 95%

Endometrial tumor necrosis factor α (TNFα) is a likely mediator of early luteal phase mifepristone-mediated negative effector action on the preimplantation embryo

Lalitkumar¹,

Sengupta²,

Ghosh³

2005

Reproduction

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Cytokines and growth factors are important mediators of progesterone-regulated endometrial receptivity and embryo development. Early luteal phase administration of a potent antiprogestin-like mifepristone to the rhesus monkey results in endometrial desynchrony, loss of embryo viability and implantation failure. In the present study, administration of mifepristone (2 mg/kg body weight, s.c.) on day 2 after ovulation resulted in a significant increase (P < 0.01) in the level of tumor necrosis factor a (TNFa) in glandular and vascular compartments of endometrium, and in endometrial secretion and luminal fluid on day 6 after ovulation in the rhesus monkey. There was an associated lag in embryonic development, characterized by delayed mitochondrial maturity, poorly developed junctional complexes, a relative absence of intra-cytoplasmic filaments and a high degree of intra-cellular degenerative features. Exposure of TNFa (0, 0.5, 5, 50 ng/ml) to preimplantation stage mouse embryos in vitro showed a dose-dependent arrest in growth and development at both morula and blastocyst stages along with ultrastructural features of degeneration similar to those observed in embryos collected from early luteal phase mifepristone-treated monkeys. The de novo synthesized and released proteins in terms of trichloroacetic acid precipitable 35 S by morulae and blastocysts in vitro showed a marked depression following exposure to TNFa compared with control embryos. Based on the above observation and the fact that preimplantation stage embryos express receptors for TNFa, we suggest that increased levels of TNFa in endometrial and luminal compartments around the time of uterine receptivity following early luteal phase administration of mifepristone adversely affect the growth and viability of preimplantation stage embryos.Reproduction (2005) 129 323-335

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“…P mixta is used as a "morning after" remedy by women of Zimbabwe to prevent pregnancy (Sewani-Rusike 2010). In order for implantation to occur, especially in the rat, the exact equilibrium of estrogen and progesterone hormones must be attained to create a milieu ideal for implantation (Psychoyos and Prapas, 1987). Thus, P. mixta showed contraceptive activity with inhibition of implantation and fertility rates, ethanolic extract being more effective than the aqueous extract (Table 1) The rat endometrium is sensitive to blastocyst signals in the morning of day 5 (Singh and Kamboj, 1992), but can experience failure of blastocyst implantation due to hostile uterine environment or hypermotility (Hafez and Hafez, 2000;Emiliani et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Antifertility effects of <i>Pouzolzia Mixta</i> in female wistar rats

Sewani-Rusike¹

2013

Afr. J. Trad. Compl. Alt. Med.

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The continued use of plants by women to prevent pregnancy suggests there are plants out there with potential use as contraceptives. In Zimbabwe, Pouzolzia mixta is used as a "morning after" contraceptive, thus it may possess postcoital antifertility activity. To test contraceptive activity, animals (n=8/group) were orally pretreated with aqueous (AqPM) or ethanolic (EtPM) extract of P. mixta at 300mg/kg b.wt for 7 days followed by mating with continued treatment for 10 days post-conception. To test for postcoital activity, treatment was initiated on day-1 of pregnancy and continued for 10 days. Laparotomy was performed and implantations counted. For estrogenic activity, immature ovariectomised rats were treated for 7 days after which vaginal opening and uterine weights were determined. In vitro oxytocic effects were performed using uterine tissue in an organ bath with De Jalon's solution. Acetylcholine (Ach) was the positive control. Results showed modest contraceptive activity with EtPM more effective in inhibiting fertility compared to AqPM (37.5% vs 25%) with a similar trend for antiimplantation effects (31% vs 19%). There was potent postcoital antifertility effects with AqPM more effective in inhibiting implantation (94.6% vs 86%) and fertility (87.5% vs 75%) compared to EtPM. Immature rat bioassay for estrogenic activity demonstrated pronounced estrogenic activity by both extracts. Oxytocic effects at 400ng/ml were more pronounced for the AqPM (92% of 100ng/ml Ach) than EtPM (25% of 100ng/ml Ach). Findings demonstrate the antifertility effects of aqueous and ethanolic extracts of P. mixta. The antifertility effects may be attributed to antiimplantation, estrogenic and oxytocic effects of the plant extracts.

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Inhibition of egg development and implantation in rats after post-coital administration of the progesterone antagonist RU 486

Cited by 64 publications

References 4 publications

Collaborative work on evaluation of ovarian toxicity 2) Two- or four-week repeated dose studies and fertility study of mifepristone in female rats

Collaborative work on evaluation of ovarian toxicity 2) Two- or four-week repeated dose studies and fertility study of mifepristone in female rats

Endometrial tumor necrosis factor α (TNFα) is a likely mediator of early luteal phase mifepristone-mediated negative effector action on the preimplantation embryo

Antifertility effects of <i>Pouzolzia Mixta</i> in female wistar rats

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