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Efficacy of various locally applied chemicals as contragestational agents in rats.

Abstract：

:Test agents were selected because of previous evidence of contragestationaal activity when administered systemically or because of known local effects which would be likely to cause endometrial changes having an adverse effect on pregnancy. A group of virgin female Sprague-Dawley rats were treated on Day 3 of pregnancy (preimplantation) and another group on Day 7 of pregnancy (postimplantation). Injections of .05 ml were made directly into the lumen of each uterine horn. Sodium chloride .9% was used on 1 side and the test agent on the other side. Implantation sites were counted before injections on Day 7. The number of corpora lutea indicated the expected number of conceptions of those injected on Day 3. On Day 15 rats were sacrificed and corpora lutea, viable conceptuses, and absorption sites were counted. Ethanol at 100, 80, 70, and 63% was a highly effective contragestational agent when given on Day 3. Formaldehyde 7-.5% was also highly effective when given on Day 3 but higher concentrations produced maternal toxicity and death. Silver nitrate, iodine, rivanol, cyclizine, urea, and 17beta-bromoacetoxy-19-nortestosterone produced no maternal toxicity but were all effective in reducing the number of viable fetuses. Prostaglandin (PGF2alpha), indomethacin, and ergonovine had no observable effect on preimplantation embryos. Methotrexate reduced survival when injected on Day 3 and more so when given on Day 7 but a systemic toxic effect was also noted. When injected on Day 7 all of the compounds except methotrexate were markedly less effective. Survival of fetuses in the control horns varied from 50% to 100%. Ethanol produced sloughing and necrosis but the endometrium appeared to be normal after 96 hours. Fecundity had not returned after 4-5 estrous cycles. The other compounds produced no histologically evident long-lasting effects. Superficial endometrial damage seemed to be the mechanism of action of compounds that were effective on Day 3. The discrepancies noted between results obtained and the documented efficiency of PGF2alpha and of urea as abortifacients in humans raises the question of the suitability of the rat as a model for predicting abortifacient activity in humans. However, the action of these 2 substances may be different in later gestational phases.

journal_name

Contraception

journal_title

Contraception

authors

Conner EA,Blake DA,Parmley TH,Burnett LS,King TM

doi

10.1016/0010-7824(76)90013-5

subject

Has Abstract

pub_date

1976-05-01 00:00:00

pages

571-82

issue

eissn

0010-7824

issn

1879-0518

pii

0010-7824(76)90013-5

journal_volume

pub_type

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Efficacy of various locally applied chemicals as contragestational agents in rats.