The Serotonin-Immune Axis in Preeclampsia

Gumusoglu, Serena B.; Scroggins, Sabrina M; Vignato, Julie; Santillan, Donna A.; Santillan, Mark K.

doi:10.1007/s11906-021-01155-4

Cited by 29 publications

(24 citation statements)

References 95 publications

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“…It has long been known that serotonin signaling plays a role in the pathogenesis of pre-eclampsia (PE), a hypertensive pregnancy disorder characterized by multiple organ dysfunction. As suggested recently ( 125 ), dysregulation of serotonin signaling may underlie several features of PE, including excessive platelet aggregation, vascular hyporeactivity, and pro-inflammation. The placentas of pregnancies complicated with PE show decreased MAOA activity ( 71 , 126 ), which may lead to decreased serotonin catabolism and contribute to the elevated circulating serotonin levels observed in women with PE.…”

Section: Serotonin System and Its Components In The Human Placentamentioning

confidence: 72%

Serotonin system in the human placenta – the knowns and unknowns

et al. 2022

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The biogenic monoamine serotonin (5-hydroxytryptamine, 5-HT) is a chemical messenger widely distributed in the brain and various other organs. Its homeostasis is maintained by the coordinated activity of a variety of proteins, including enzymes of serotonin metabolism, transmembrane transporters of serotonin, and serotonin receptors. The serotonin system has been identified also in the placenta in rodent models as a key component of placental physiology. However, serotonin pathways in the human placenta are far from well understood. Their alterations may have long-lasting consequences for the fetus that can manifest later in life. In this review, we summarize information on the location of the components of the serotonin system in the human placenta, their regulation, function, and alterations in pathological pregnancies. We highlight current controversies and discuss important topics for future research.

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Section: Serotonin System and Its Components In The Human Placentamentioning

confidence: 72%

Serotonin system in the human placenta – the knowns and unknowns

et al. 2022

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“…Serotonin regulates physiological processes including bone and calcium metabolism, energy homeostasis, gastrointestinal motility, brain development, and vascular resistance, among numerous other functions [1,2,[4][5][6]. 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).…”

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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“…PE can have an early or late onset, range from mild to severe illness, and be associated with various maternal predisposing factors, including chronic hypertension, pre-existing diabetes mellitus, multifetal pregnancies, nutritional factors, maternal immunological alterations, genetic susceptibility, and history of PE in the previous pregnancy [32][33][34][35][36]. In terms of genetic susceptibility, serotonergic dysregulation appears to play a role in the etiology of PE [37][38][39].…”

Section: Introductionmentioning

confidence: 99%

“…Since the 1960s, serotonin (5-HT) was proposed as a factor involved in poor placental perfusion, as it was found in the placentas of women with PE [40]. Later, the study of the 5-HT transporter gene (5-HTT or SERT) variants showed a relationship between the risk of developing changes in the placental microvasculature [38,41] and the 5-HTT expression in the apical membrane of the placental syncytiotrophoblast [42,43]. Tryptophan, a precursor of 5-HT, also revealed its regulatory role in promoting better maternal-fetal tolerance [44].…”

Section: Introductionmentioning

confidence: 99%

The S/S Genotype of the 5-HTTLPR (Serotonin-Transporter-Linked Promoter Region) Variant of the SLC6A4 Gene Decreases the Risk of Pre-Eclampsia

Ramírez-Armas,

Garza-Veloz,

Olivas-Chávez

et al. 2023

JPM

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Pre-eclampsia (PE) is a disorder characterized by hypertension in the second trimester of pregnancy that results from abnormal placentation affecting fetal development and maternal health. Previous studies have shown the role of serotonin (5-HT) that leads to poor placental perfusion, where S/S and S/L polymorphisms promote the solute carrier family 6 member 4 (SLC6A4) gene associated with the risk of developing changes in the microvasculature of the placenta. This study looked at the association between the gene variant 5-HTTLPR (serotonin-transporter-linked promoter region) of the SLC6A4 gene and the occurrence of PE. A total of 200 women were included: 100 cases (pregnant with PE) and 100 controls (pregnant without complications). Genotyping of the 5-HTTLPR variant was performed using polymerase chain reaction (PCR). Associations between the presence of the genetic variant of interest and PE and other clinical features were evaluated statistically. The frequencies of S/S, S/L, and L/L genotypes were 32%, 53%, and 15% for the cases and 55%, 25%, and 20% in the control group. Compared to the controls, the genotype frequencies S/S vs. S/L + L/L (recessive model) in the cases group were different (p = 0.002). The S/S genotype decreased the probability of PE (OR = 0.39, 95% IC: 0.22–0.69, p = 0.002) and PE with severity criteria (OR = 0.39, 95% IC: 0.17–0.91, p = 0.045). The 5-HTTLPR gene variant of the SLC6A4 gene modifies the risk of PE development among the studied population.

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The Serotonin-Immune Axis in Preeclampsia

Cited by 29 publications

References 95 publications

Serotonin system in the human placenta – the knowns and unknowns

Serotonin system in the human placenta – the knowns and unknowns

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

The S/S Genotype of the 5-HTTLPR (Serotonin-Transporter-Linked Promoter Region) Variant of the SLC6A4 Gene Decreases the Risk of Pre-Eclampsia

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