Anti-implantation activity of antiestrogens and mifepristone

Dao, Blami; Vanage, Geeta; Marshall, A.; Bardin, C. Wayne; Koide, S. S.

doi:10.1016/s0010-7824(96)00196-5

Cited by 32 publications

(14 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 50%

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

View full text Add to dashboard Cite

-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-

show abstract

Section: Discussioncontrasting

confidence: 50%

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

View full text Add to dashboard Cite

show abstract

“…Embryo implantation can be prevented by removal of ovarian estrogen [11] and interference of estrogen interactions with its receptor [12]. We evaluated the effect of disrupting estrogen receptor signaling on blastocyst adhesiveness ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…1 A ). Pregnant mice were treated with an estrogen competitor, tamoxifen (TAM) [12], [13], on E2.5 and blastocysts were collected on E4.0 (E4.0 TAM). Blastocysts were also collected from intact pregnant mice on E3.5 or E4.0 (E3.5 Ctrl and E4.0 Ctrl, respectively) and examined for their affinity for FN using a rhodamine-FN binding assay.…”

Section: Resultsmentioning

confidence: 99%

Estrogen-Dependent Uterine Secretion of Osteopontin Activates Blastocyst Adhesion Competence

Chaen

Konno²,

Egashira³

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

Embryo implantation is a highly orchestrated process that involves blastocyst-uterine interactions. This process is confined to a defined interval during gestation referred to as the “window of embryo implantation receptivity”. In mice this receptive period is controlled by ovarian estrogen and involves a coordination of blastocyst adhesion competence and uterine receptivity. Mechanisms coordinating the acquisition of blastocyst adhesion competence and uterine receptivity are largely unknown. Here, we show that ovarian estrogen indirectly regulates blastocyst adhesion competence. Acquisition of blastocyst adhesion competence was attributed to integrin activation (e.g. formation of adhesion complexes) rather than de novo integrin synthesis. Osteopontin (OPN) was identified as an estrogen-dependent uterine endometrial gland secretory factor responsible for activating blastocyst adhesion competence. Increased adhesion complex assembly in OPN-treated blastocysts was mediated through focal adhesion kinase (FAK)- and phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathways. These findings define for the first time specific regulatory components of an estrogen-dependent pathway coordinating blastocyst adhesion competence and uterine receptivity.

show abstract

“…The antiestrogen ICI 182780 was given at doses known to prevent implantation [Dao et al, 1996] and to block E 2 , [Runic et al, 1996], and the aromatase inhibitor LTZ at doses proven to inhibit implantation in the rat (not shown).…”

Section: Drugsmentioning

confidence: 99%

“…Either the antiprogestin RU486 at a dose of 1-3 mg/day on days 1-4 postcoitaly [Roblero & Croxatto, 1991] or the estrogen receptor antagonist ICI 182780 at a dose of 0.1 mg/kg/day on days 1-3 prevent implantation in rats [Dao et al, 1996]. On the other hand, treatment with RU 486 combined with an aromatase inhibitor, either aminoglutethimide or letrozole (LTZ) both given at subtreshold doses acts synergistically to block implantation in rats [Shi et al, 2003].…”

Section: Introductionmentioning

confidence: 99%

Progesterone, but not luteal estrogen, is required for the establishment of pregnancy in the new world monkey Cebus apella

Ortiz¹,

Ortíz²,

Garfield³

et al. 2007

American J Primatol

View full text Add to dashboard Cite

The aim of this study was to examine the requirement of luteal progesterone or luteal estrogen for the establishment of pregnancy in the Cebus monkey and to test in a primate species the synergism between RU 486 and letrozole (LTZ) found in rodents for inhibiting implantation. Exposure of target tissues to either hormone was suppressed during the mid-luteal phase of mating cycles by subcutaneous administration of the antiprogestin (RU 486), the aromatase inhibitor LTZ or the antiestrogen (ICI 182780) on days 4-7 of the luteal phase. Administration of 0.1 or 0.5 mg/kg of LTZ on days 5-7 of the luteal phase caused a profound drop in the levels of E(2) in all animals, whereas administration of ICI 182780 0.2 mg/kg on days 4-6 of the luteal phase had the opposite effect. The pregnancy rate in vehicle treated cycles of the same females was (58.3%). Treatment with RU 486, 0.8 mg/kg/day on days 5-7 of the luteal phase-induced endometrial bleeding in 3/5 mated females none of which became pregnant, whereas pregnancy was confirmed in one of the two animals that did not bled. Treatment with RU 486, 0.4 mg/kg/day alone or with LTZ on days 5-7 or ICI 182780 alone, on days 4-6 of the luteal phase failed to induce bleeding, allowing the establishment of pregnancy in 50.0-66.6% of the animals in these groups. We conclude that in Cebus monkeys, progesterone but not luteal estradiol is required for the establishment of pregnancy and that RU 486 and LTZ do not exhibit in this species the synergism found in rodents.

show abstract

Anti-implantation activity of antiestrogens and mifepristone

Cited by 32 publications

References 12 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

Estrogen-Dependent Uterine Secretion of Osteopontin Activates Blastocyst Adhesion Competence

Progesterone, but not luteal estrogen, is required for the establishment of pregnancy in the new world monkey Cebus apella

Contact Info

Product

Resources

About