The 5‐hydroxytryptamine Content of the Placenta and Foetus During Pregnancy in Mice

Robson, J. M.; Senior, Judith

doi:10.1111/j.1476-5381.1964.tb02043.x

Cited by 24 publications

(25 citation statements)

References 7 publications

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“…The impact of maternal SERT genotype on forebrain 5-HT levels is surprising because previous work found that 5-HT does not cross the maternal-fetal barrier (Robson and Senior, 1964), and its synthesis in the placenta is dependent upon embryo genotype (Bonnin et al, 2011). The observed developmental trajectory of forebrain 5-HT, however, suggests that altered maternal 5-HT homeostasis impacts the placenta.…”

Section: Discussionmentioning

confidence: 38%

“…Interestingly, SERT Ala56 dams exhibited a transient increase in blood 5-HT levels at E14.5. As maternal 5-HT cannot cross the placenta into fetal circulation (Bonnin et al, 2011;Robson and Senior, 1964), it is unlikely that changes in maternal 5-HT blood levels would directly affect placental or fetal forebrain 5-HT levels. Syncytiotrophoblasts, the cellular interface between the maternal and fetal blood supply in the placenta, are thought to tightly regulate free 5-HT via MAOA degradation (Wu et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

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Impact of Maternal Serotonin Transporter Genotype on Placental Serotonin, Fetal Forebrain Serotonin, and Neurodevelopment

Muller

Anacker

Rogers

et al. 2016

Neuropsychopharmacol

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Biomarker, neuroimaging, and genetic findings implicate the serotonin transporter (SERT) in autism spectrum disorder (ASD). Previously, we found that adult male mice expressing the autism-associated SERT Ala56 variant have altered central serotonin (5-HT) system function, as well as elevated peripheral blood 5-HT levels. Early in gestation, before midbrain 5-HT projections have reached the cortex, peripheral sources supply 5-HT to the forebrain, suggesting that altered maternal or placenta 5-HT system function could impact the developing embryo. We therefore used different combinations of maternal and embryo SERT Ala56 genotypes to examine effects on blood, placenta and embryo serotonin levels and neurodevelopment at embryonic day E14.5, when peripheral sources of 5-HT predominate, and E18.5, when midbrain 5-HT projections have reached the forebrain. Maternal SERT Ala56 genotype was associated with decreased placenta and embryonic forebrain 5-HT levels at E14.5. Low 5-HT in the placenta persisted, but forebrain levels normalized by E18.5. Maternal SERT Ala56 genotype effects on forebrain 5-HT levels were accompanied by a broadening of 5-HT-sensitive thalamocortical axon projections. In contrast, no effect of embryo genotype was seen in concepti from heterozygous dams. Blood 5-HT levels were dynamic across pregnancy and were increased in SERT Ala56 dams at E14.5. Placenta RNA sequencing data at E14.5 indicated substantial impact of maternal SERT Ala56 genotype, with alterations in immune and metabolic-related pathways. Collectively, these findings indicate that maternal SERT function impacts offspring placental 5-HT levels, forebrain 5-HT levels, and neurodevelopment.

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Section: Discussionmentioning

confidence: 38%

Section: Discussionmentioning

confidence: 99%

Impact of Maternal Serotonin Transporter Genotype on Placental Serotonin, Fetal Forebrain Serotonin, and Neurodevelopment

Muller

Anacker

Rogers

et al. 2016

Neuropsychopharmacol

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“…Mouse erythrocytes labelled with chromium were therefore used and this has proved very satisfactory. The method of labelling the cells has been described by Robson & Senior (1964); a volume of 0-2-0-3 ml. of a suspension with an activity of 100lC/ml.…”

Section: -Ht and Pregnancy 721mentioning

confidence: 99%

“…The tissues were extracted and assayed both biologically and fluorometrically as described by Robson & Senior (1964). All the results of assays are expressed in terms of 5-HT base.…”

Section: -Ht and Pregnancy 719mentioning

confidence: 99%

Analysis of actions of 5‐hydroxytryptamine in pregnancy

Robson¹,

Sullivan²

1966

The Journal of Physiology

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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...

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“…

Several workers (Nachmias, 1960;Karki, Kuntzman & Brodie, 1962) have investigated the level of 5HT in the brain of the newborn rat, and have found it to be about one-third of that found in the adult rat brain.

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confidence: 99%

The 5‐hydroxytryptamine Content of the Placenta, Foetus and Some Maternal Tissues During Pregnancy in the Rat

Fahim¹,

Robson²,

Senior³

1966

British Journal of Pharmacology and Chemotherapy

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The results obtained from the measurement of the 5-hydroxytryptamine (5HT) content of mouse tissue during pregnancy (Robson & Senior, 1964) led us to undertake a similar investigation in the rat. Dixon (1959) measured the 5HT level in rat foetuses, and found that it reached a peak on the first day after birth, after rising steadily from about the fifteenth day of gestation.Several workers (Nachmias, 1960;Karki, Kuntzman & Brodie, 1962) have investigated the level of 5HT in the brain of the newborn rat, and have found it to be about one-third of that found in the adult rat brain. Nachmias (1960) also showed that the amount of amine oxidase in the rat brain at birth was much lower than in the adult brain.In the current experiments the levels of 5HT in the placenta and foetus have been measured in the second half of pregnancy, as have some of the levels in other maternal tissues. In an attempt to account for the amount of 5HT found in the untreated placenta, the maternal blood content of the placenta in the latter half of pregnancy was measured, and this was correlated with the maternal blood level of 5HT. Following the findings by Correll, Lyth, Long & Vanderpoel (1952) and Waugh & Pearl (1960) that 5HT produced deleterious effects on pregnancy in the rat, the level of 5HT was measured in the placenta and foetus after the administration of this drug. As 5HT treatment of the mother caused a rise in the 5HT level of the placenta it seemed of interest to investigate the effect of monoamine oxidase inhibitors, particularly as these substances had failed to change the level of 5HT in the mouse placenta (Robson & Senior, 1964). METHODSThe experiments were performed on mature Wistar albino rats, weighing 250 to 400 g. They were housed in the Animal House, Guy's Hospital Medical School, and allowed food and water ad libitum. The food consisted of rat cake obtained from the North East Agricultural Society, Aberdeen. The pregnancy was dated by finding spermatazoa in the vaginal smear. The animal was then isolated from the male and pregnancy was confirmed from the 12th day onward by palpation.

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The 5‐hydroxytryptamine Content of the Placenta and Foetus During Pregnancy in Mice

Cited by 24 publications

References 7 publications

Impact of Maternal Serotonin Transporter Genotype on Placental Serotonin, Fetal Forebrain Serotonin, and Neurodevelopment

Impact of Maternal Serotonin Transporter Genotype on Placental Serotonin, Fetal Forebrain Serotonin, and Neurodevelopment

Analysis of actions of 5‐hydroxytryptamine in pregnancy

The 5‐hydroxytryptamine Content of the Placenta, Foetus and Some Maternal Tissues During Pregnancy in the Rat

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