Biology of Reproduction, Vol 21, 47-52, Copyright © 1979 by Society for the Study of Reproduction

Implantation and Fetal Survival in the Rat as Affected by Intrauterine Injection of Normal Sterile Saline

¹ Department of Gynecology and Obstetrics, The Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205

The pregnant rat has been used as a model for the testing of drugs applied directly into the uterus to determine their effects on implantation and fetal viability. Because of current interest in developing new contraceptive agents, it appeared pertinent to define the experimental model more precisely. Timed pregnant rats were laparotomized under light ether anesthesia. A sterile 25 gauge needle attached to a 1 ml tuberculin syringe was inserted into the lumen of 1 uterine horn at the cervical end. Sterile saline (0.1 ml, 0.9%) was injected into the horn on 1 occasion between Days 3-9 of pregnancy (day sperm found in vagina = Day 1). Rats were autopsied on Day 15. Percent implantation (number of sites/number of corpora lutea) was decreased when 0.1 ml saline was injected on Day 4, but not affected by injection on any other day. Fetal viability (number of viable fetuses/number of sites) was decreased by the injection of 0.1 ml saline on Days 4, 5, 6 or 7; the greatest effect was observed with injection on Day 6. On this day complete resorption occurred in the injected horn of 26 of 28 rats. No effect was observed in untreated contralateral horns. Complete fetal resorption could be effected by injection on Day 6 of 0.1 ml saline into both horns. Decreasing the volume of saline injected on Day 6 resulted in a decrease in the number of resorbed sites. Day 6 sham controls (needle inserted but nothing injected) showed normal fetal viability. Uterine horns injected on Day 6, when observed histologically on Day 9, contained implanted blastocysts. However, undifferentiated cells were seen in the blastocyst cavity along with maternal blood cells, typical of a resorbing blastocyst. These data illustrate that intrauterine normal saline may greatly affect fetal viability depending on the volume and the day of injection; thus defining some limitations of the model as used for antifertility drug testing. The results also describe an animal model with which physiologic correlates of the resorption process can be studied.

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ACKNOWLEDGMENTS These studies were supported by contract USAID/ CSD-3627. We thank Susan Scheper and Jean Duncan for preparing the manuscript.