Serotonin-induced disruption of implantation in the rat: I. Serum progesterone, implantation site blood flow, and intrauterine pO₂

Serotonin, administered on the day after the initiation of implantation, promptly terminates pregnancy in the rat. Consequently, the effects of serotonin on serum progesterone levels, implantation site blood flow, and intrauterine oxygen tension were determined to see whether the disruption of implantation is related to altered corpus luteum and/or uterine vascular function. Animals received a subcutaneous injection of physiological saline (C: control) or serotonin (S: 20 mg/kg) on day 5 of pregnancy. Serotonin did not alter the number of blastocysts implanting (C: 6.02 ± 0.52 vs. S: 6.29 ± 0.46, sites/cornu) but did cause subsequent implantation site resorption (C: 0.08 ± 0.07 vs. S: 5.46 ± 0.44/cornu; P < 0.001). Progesterone levels in serotonin-treated rats did not differ from those of controls at 6 hr postinjection or on days 6 through 10 of pregnancy. Implantation site blood flow was reduced at 30 min (C: 0.76 ± 0.12 vs S: 0.25 ± 0.02 ml/min per g; P < 0.01) and remained suppressed at 2 hr after serotonin injection. A prompt and sustained reduction in intrauterine oxygen tension (C: 48.9 ± 3.7 vs S: 25.9 ± 4.5 mmHg; P < 0.005; 120 min) accompanied the reduced uterine perfusion. Thus, disruption of implantation is not a result of impaired corpus luteum function but is associated with marked and protracted reductions in uterine blood flow and intraluminal oxygen availability.