Analysis of actions of 5‐hydroxytryptamine in pregnancy

Abstract

SU'MARY 1. When 5-hydroxytryptamine creatinine sulphate is injected subcutaneously in a dose of 2 mg into mice during the second halfofpregnancy, the foetuses die within 1 hr. The mode of action of 5-hydroxytryptamine (5-HT) in producing this effect has been studied.2. It has been demonstrated that this is not a direct toxic effect of 5-HT.Very little passes through the placenta into the foetus, and after the injection of much larger amounts directly into the foetus no lethal effect was observed.3. It was shown that 5-HT had little effect on uterine motility in vivo, and that the much larger contractions produced by oxytocin did not produce any effect on the foetus. 4. No constriction of the umbilical vessels was produced by 5-HT injected into the mother, nor did the local application of 5-HT to the cord produce any effect.5. The administration of 5-HT to the mother markedly reduced the passage of 22Na from the maternal circulation into the placenta and foetus. This was accompanied by a reduction in the blood supply to the placenta from a normal value of 87 gl./min/g to 4 ,/g/min/g. 6. It is suggested that the effect of 5-HT in producing foetal death is a consequence of the reduction in the transfer function of the placenta. INTRODUCTIONIt has been shown previously that 5-HT will interfere with pregnancy in mice at all stages. In the first half of pregnancy the effect occurs when the drug is given daily for several days, e.g. from the first to sixth day, and appears to be due to an interference with the hormonal mechanism responsible for the maintenance of gestation (Lindsay, Poulson & Robson, 1963).In the second half of pregnancy the effect of 5-HT comes on very rapidly 718 J. M. ROBSON AND F. M. SULLIVAN and usually causes death of the foetuses within 0-5 hr following a single injection (Poulson, Botros & Robson, 1960). It seemed likely at first that this was due to a direct toxic effect of the drug on the foetus, but this was found not to be so. The lethal action of 5-fHT was thus investigated systematically and the experiments described in this paper illustrate our approach to the problem. They can be subdivided under these headings:(a) Direct effect of 5-HT on the foetus. (b) Effect on uterine activity in vivo.(c) Action on vessels of the umbilical cord.(d) Effect on the passage of radio-sodium from the mother into the placenta and foetus.(e) Effect on the maternal blood supply to the placenta. METHODS Experiments were performed on white mice bred in the Animal House of Guy's Hospital Medical School. The mice were kept in groups of five females and one male and vaginal plugs looked for daily. The day of finding the vaginal plug is called day 1 of pregnancy.5-Hydroxytryptamine creatinine 8uphate. 5-Hydroxytryptamine creatinine sulphate (May & Baker) was used throughout and the doses given are expressed in terms of the salt. To produce the lethal effect on the foetus a standard dose of 2 mg of the salt (equivalent to 0*87 mg of base) was given subcutaneously to the mother.Anaethe8ia. Ether was used in the ear...

Suppression of trophoblast uterine spiral artery remodeling by estrogen during baboon pregnancy: impact on uterine and fetal blood flow dynamics

“…5-HT is transferred via a transporter across the placental syncytiotrophoblast (7,62), where it has the capacity to induce umbilical artery contraction (35,50,56,61). Many studies have shown that normal pregnancy suppresses the pressor responses of uterine and umbilical arteries to various vasoconstrictors, including 5-HT, angiotensin II, and epinephrine (19,52,53,65,66), and this process appears to be mediated by endothelium-dependent mechanisms, e.g., nitric oxide or prostacyclin (67).…”

Serotonin Metabolism in Normal and Abnormal Infants during the Perinatal Period

“…Brzezinski et al (1962) have maintained that placental monoamine oxidase (MAO) forms a barrier which completely prevents the passage of 5-HT from the maternal to the fetal circulation, but Robson and Sullivan (1966) and Koren et al (1966) demonstrated that portions of 5-HT did pass through the placenta into the fetus after the injection of the amine into the maternal circula tion. Although excessive 5-HT in the maternal blood is known to be toxic to the fetus {Reddy Southgate and Sandler, 1968), an optimal level of 5-HT is considered by Baker and Quay (1969) to be essential for embryogenesis.…”

Effect of the Serotonin Antagonist Cyproheptadine on Uterine and Duodenal Muscle Contractions in Rats

“…It may, therefore, be responsible for abortion either by causing uterine contractions or by decreasing placental blood flow re sulting in ischemia and fetal death [8,9,14,[17][18][19][20]. Normally, uterine serotonin is metabolized by the enzyme monoamine oxidase (MAO) to…”

“…High quantities of serotonin alone will not cause abortion as long as amniotic MAO, which metabolizes serotonin to 5-HIAA, prevents any noxious serotonin effect on the fetus [15,17,19,20]. When this protective enzyme system breaks down, excess serotonin accumulates in the estrogensensitized myometrium and may cause abortion or fetal death [2,8,9,12,18], Serotonin abortion was produced in pregnant rats by blocking their uterine MAO system following intraamniotic injection of the MAO inhib itor (MAOI) pargyline (Eutonyl-Abbot).…”