Embryotoxic Effects of 5-Hydroxytryptamine During the Peri-implantation Period in the Rat

Abstract

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.

Embryonic mortality and intrauterine growth retardation (IUGR) associated with placental alterations in pregnant rats treated with methyl methanesulfonate (MMS) at the peri-implantation stage

“…The trophoblast begins to invade the endometrium on GD6 (Tachi et al, 1970), and the trophoblast cells establish direct contact with cells of the stroma on GD7 (Tachi et al, 1970). The peri-implantation period in rats thus begins at ~18:00 hr on GD4 and ends at ~15:00 hr of GD6 (Aliverti et al, 1982). After implantation, a yolk sac with an extensive vitelline circulation forms between GD7 and GD11 (Huggett and Pritchard, 1945).…”

Differential Susceptibility of Rat Embryos to Methyl Methanesulfonate During the Pregastrulation Period

“…Each group of dams was treated orally with a single dose of MMS (200 mg per kg of body mass) in the morning of gestation days 0, 1, 2, 3, 4, 5, or 6, with the corresponding experimental groups being designated GD0 to GD6, respectively. These times of MMS administration represent developmental stages were the zygote (GD0), two-cell (GD1), two-to four-cell (GD2), eight-cell/ morula (GD3), blastocyst (GD4), hatched blastocyst/ initiation of implantation (GD5) and implantation (GD6), respectively (Witschi, 1962;Yasuda and Sato, 1980;Aliverti et al, 1982;Graeter et al, 1998). The dose (200 mg/kg) was chosen based on the oral LD50 for rats (225 mg/kg, Material Safety Data Sheet, http:// p h y s c h e m .…”