Serotonin system in the human placenta – the knowns and unknowns

Perić, Maja; Bečeheli, Ivona; Čičin‐Šain, Lipa; Desoyé, Gernot; Štefulj, Jasminka

doi:10.3389/fendo.2022.1061317

Cited by 9 publications

(7 citation statements)

References 151 publications

(253 reference statements)

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“…Several nutrients contained within the BSM formula used in the current study are known co-factors required for the synthesis of serotonin, a neurotransmitter linked to emotion regulation ( 68 ). It is possible that increasing maternal concentrations of vital nutrient co-factors in pregnancy may influence both maternal and fetal serotonin production ( 69 ), impacting emotion regulation a key component of temperament.…”

Section: Introductionmentioning

confidence: 99%

Exploring the impact of antenatal micronutrients used as a treatment for maternal depression on infant temperament in the first year of life

Campbell,

Dys,

Henderson

et al. 2024

Front. Nutr.

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Antenatal depression and maternal nutrition can influence infant temperament. Although broad-spectrum-micronutrients (BSM: vitamins and minerals) given above Recommended Dietary Allowances during pregnancy can mitigate symptoms of antenatal depression, their associated effects on infant temperament are unknown. One hundred and fourteen New Zealand mother-infant dyads (45 infants exposed to BSM during pregnancy (range of exposure during pregnancy: 12–182 days) to treat antenatal depressive symptoms (measured by Edinburgh Postnatal Depression Scale) and 69 non-exposed infants) were followed antenatally and for 12 months postpartum to determine the influence of in utero BSM exposure on infant temperament. The Infant Behavior Questionnaire–Revised: Very Short-Form assessed temperament at 4 (T1), 6 (T2) and 12 (T3) months postpartum via online questionnaire. Latent growth curve modeling showed BSM exposure, antenatal depression and infant sex did not statistically significantly predict initial levels or longitudinal changes in orienting/regulatory capacity (ORC), positive affectivity/surgency (PAS) or negative affectivity (NEG). Higher gestational age was positively associated with initial PAS, and smaller increases between T1 and T3. Breastfeeding occurrence was positively associated with initial NEG. Although not significant, BSM exposure exerted small, positive effects on initial NEG (β = −0.116) and longitudinal changes in ORC (β = 0.266) and NEG (β = −0.235). While BSM exposure did not significantly predict infant temperament, it may mitigate risks associated with antenatal depression. BSM-exposed infants displayed temperamental characteristics on par with typical pregnancies, supporting the safety of BSM treatment for antenatal depression.

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Section: Introductionmentioning

confidence: 99%

Exploring the impact of antenatal micronutrients used as a treatment for maternal depression on infant temperament in the first year of life

Campbell,

Dys,

Henderson

et al. 2024

Front. Nutr.

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“…For decades, altered serotonin signaling has been implicated in the pathophysiology of hypertension, preeclampsia, and neurodevelopment disorders in infants [5,[7][8][9][10][11][12][13][14]. Additionally, serotonin's effects on pregnancy outcomes have been studied for decades; however, more recently, the role of serotonin in processes including embryonic and fetal brain development, placental function, intrauterine growth restriction (IUGR), and neonatal health have been in the spotlight [13,[15][16][17][18][19][20] given the increasing maternal use of medications that alter serotonin signaling, including selective serotonin reuptake inhibitors (SSRI). The possible detrimental effects of serotonin on pregnancy and neonatal outcomes support the need for a comprehensive understanding of how serotonin and medications that modulate serotonin signaling are associated with the pathophysiology of multiple conditions, such as gestational hypertension, preeclampsia, IUGR, autism spectrum disorder, preterm birth, and sudden infant death syndrome.…”

Section: Introductionmentioning

confidence: 99%

Maternal serotonin: implications for the use of selective serotonin reuptake inhibitors during gestation

Domingues

Wiltbank

Hernández

2023

Biology of Reproduction

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Maternal use of antidepressants has increased throughout the last decades; selective serotonin reuptake inhibitors (SSRI) are the most prescribed antidepressants. Despite the widespread use of SSRI by women during reproductive age and pregnant women, an increasing amount of research warns of possible detrimental effects of maternal use of SSRI during pregnancy including low birthweight/small for gestational age and preterm birth. In this review we revisited the impact of maternal use of SSRI during pregnancy, its impact on serotonin homeostasis in the maternal and fetal circulation and in the placenta, and its impact on pregnancy outcomes – particularly intrauterine growth restriction and preterm birth. Maternal use of SSRI increases maternal and fetal serotonin. The increase in maternal circulating serotonin and serotonin signaling likely promotes vasoconstriction of the uterine and placental vascular beds decreasing blood perfusion to the uterus and consequently to the placenta and fetus with potential impact on placental function and fetal development. Several adverse pregnancy outcomes are similar between women, sheep, and rodents (decreased placental size, decreased birthweight, shorter gestation length/preterm birth, neonatal morbidity and mortality) highlighting the importance of animal studies to assess the impacts of SSRI. Herein, we address the complex interactions between maternal SSRI use during gestation, circulating serotonin, and the regulation of blood perfusion to the uterus and fetoplacental unit, fetal growth, and pregnancy complications.

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“…TRP metabolism via the 5-HT pathway produces active metabolites such as 5-HT and melatonin [ 19 ]. The key enzymes of this pathway are tryptophan hydroxylase (TPH), which is the pathway’s first and rate-limiting enzyme, and monoamine oxidase (MAO), which degrades 5-HT [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Pathological shifts in tryptophan metabolism in human term placenta exposed to LPS or poly I:C

Abad,

Karahoda,

Orbisova

et al. 2023

Biology of Reproduction

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Maternal immune activation during pregnancy is a risk factor for offspring neuropsychiatric disorders. Among the mechanistic pathways by which maternal inflammation can affect fetal brain development and programming, those involving tryptophan (TRP) metabolism have drawn attention because various TRP metabolites have neuroactive properties. This study evaluates the effect of bacterial (LPS) and viral (poly I:C) placental infection on TRP metabolism using an ex vivo model. Human placenta explants were exposed to LPS or Poly I:C, and the release of TRP metabolites was analyzed together with the expression of related genes and proteins and the functional activity of key enzymes in TRP metabolism. The rate-limiting enzyme in the serotonin pathway, tryptophan hydroxylase, showed reduced expression and functional activity in explants exposed to LPS or Poly I:C. Conversely, the rate-limiting enzyme in the kynurenine (KYN) pathway, indoleamine dioxygenase, exhibited increased activity, gene, and protein expression, suggesting that placental infection mainly promotes TRP metabolism via the KYN pathway. Furthermore, we observed that treatment with LPS or Poly I:C increased activity in the kynurenine monooxygenase branch of the KYN pathway. We conclude that placental infection impairs TRP homeostasis, resulting in decreased production of serotonin and an imbalance in the ratio between quinolinic acid and kynurenic acid. This disrupted homeostasis may eventually expose the fetus to suboptimal/toxic levels of neuroactive molecules and impair fetal brain development.

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Serotonin system in the human placenta – the knowns and unknowns

Cited by 9 publications

References 151 publications

Exploring the impact of antenatal micronutrients used as a treatment for maternal depression on infant temperament in the first year of life

Exploring the impact of antenatal micronutrients used as a treatment for maternal depression on infant temperament in the first year of life

Maternal serotonin: implications for the use of selective serotonin reuptake inhibitors during gestation

Pathological shifts in tryptophan metabolism in human term placenta exposed to LPS or poly I:C

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