Embryotoxic effects of 5-hydroxytryptamine during the peri-implantation period in the rat.

Administration of 5-hydroxytryptamine creatinine sulphate (5-HT) 5-10-20 mg/kg s.c. to pregnant rats during the preimplantation period (1200 h, Days 1 through 5) did not inhibit implantation. Experiment 2: Administration to pregnant rats during the peri-implantation period (0900 h, Day 6) of 5-HT 5 mg/kg s.c. did not affect implantation or embryo-fetal development. 5-HT 10 mg/kg s.c. produced a significant increase (P greater than 0.01) in the resorption rate (31.8%) and severe cardiovascular or ophthalmic malformations in 5.3% of viable fetuses. 5-HT 20 mg/kg produced a resorption rate (97.2%) virtually incompatible with the continuance of pregnancy. Experiment 3: Histological examination of uterine preparations made from Day 6 pregnant rats sacrificed 6, 24, and 30 h after receiving 5-HT 20 mg/kg s.c. showed, in 30 h post-injection preparations, toxic effects at implantation sites (uterine lumen completely deprived of epithelial layer and filled with cellular debris, and complete degeneration of implanted embryos) but no toxic effects between implantation sites. Experiment 4: Administration of 5-HT 10 mg/kg s.c. to pregnant rats during the postimplantation period (Days 10 and 11) produced a 63.2% resorption rate, a reduction in the mean weight of viable fetuses, and severe malformations in 24% of viable fetuses. The embryotoxic activity of 5-HT may be attributed to its vasoconstrictive action which renders the uterine mucosa or trophoblast ischemic, thus causing irreversible damage to the luminal epithelium at the implantation sites.