Effects of indomethacin on uterine capillary permeability and blastocyst development in rabbits

Increased capillary permeability at implantation sites was demonstrated in rabbits by extravasation of intravascular blue dye on day 7 of pregnancy. Subcutaneous administration of indomethacin (Id, 8 mg/kg twice daily) on days 4-6 of pregnancy inhibited this uterine blueing response and appeared to reduce the size of implantation swellings. To test the latter observation blastocyst diameter and development of the embryonic disk were assessed at 144 hr post coitum. In females receiving indomethacin at the dose level which inhibited uterine blueing, blastocysts were significantly smaller than those from control females. Developmental staging of embryonic disks revealed only slight differences between the smaller (Id-treated) blastocysts and control blastocysts. No effect of Id was seen on ovarian function as judged by luteal weights and plasma progesterone and estradiol levels. Since the major biological effects of indomethacin are due to its inhibition of prostaglandin synthesis, it appears that prostaglandins may play a role in the uterine response to blastocyst stimulation and in the expansion of blastocysts in the rabbit.