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Biology of Reproduction, Vol 25, 777-784, Copyright © 1981 by Society for the Study of Reproduction

Further Effects of Nonsteroidal Anti-inflammatory Compounds on Blastocyst Hatching in vitro and Implantation Rates in the Mouse

P. R. HURST 1, and D. W. MacFARLANE 1

1 Department of Anatomy, The Medical School, University of Otago, Dunedin, New Zealand


When tested in protein-free medium NCTC 109, mouse blastocyst hatching in vitro was inhibited by low doses (<50 µM) of indomethacin, meclofenamic acid, mefenamic acid, and naproxen. Ketoprofen was not inhibitory within the same concentration range. In medium supplemented with 10% fetal calf serum, meclofenamic acid inhibited hatching above 100 µM but in contrast naproxen had no effect at 500 µM. By ultrafiltration plus HPLC analysis, it was found that for meclofenamic acid over the range 100-200 µM, 92-83% was bound to 10% fetal calf serum.

Cinemicrographic recording of supplemented cultures containing 100 to 150 µM meclofenamic acid revealed that the principal reason for the inhibition of hatching was the prevention of adequate blastocyst expansion which is a normal prerequisite to hatching in vitro.

Intrauterine administration of 160 µM meclofenamic acid to one horn of pregnant mice on Day 4 significantly reduced the rate of implantation.

Note:
ACKNOWLEDGMENTS We are grateful to Mr. D. G. Ferry (M.R.C. Toxicology Research Unit, Dunedin) for advice and help with the HPLC; Dr. R. J. Harvey (Anatomy Dept.) and George Spears (Preventive and Social Medicine Dept.) for consultation and assistance with the statistics; and Linda Scott for typing the manuscript.

Submitted on March 9, 1981
Accepted on July 7, 1981




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Copyright © 1981 by the Society for the Study of Reproduction.