Functional characterization of dopamine and norepinephrine transport across the apical and basal plasma membranes of the human placental syncytiotrophoblast

Horackova, Hana; Karahoda, Rona; Váchalová, Veronika; Turková, Hana; Abad, Cilia; Štaud, František

doi:10.1038/s41598-022-15790-7

Cited by 7 publications

(2 citation statements)

References 57 publications

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“…Therefore, increased GCM1 due to BPS exposure could indirectly impact cognitive functions. Moreover, a reduction in dopamine and serotonin content of the BPS-exposed placenta was also reported [31], both of which play roles in the fetal brain structures and functions [51,71]. On the other hand, BPA alternatives may alter the child's neurodevelopment and motor skills via their roles in interfering with specific hormone activities, including thyroid hormones.…”

Section: Effects On Cognitive Functions and Psychomotor Skillsmentioning

confidence: 95%

Effects of Prenatal Exposure to Bisphenol A Substitutes, Bisphenol S and Bisphenol F, on Offspring’s Health: Evidence from Epidemiological and Experimental Studies

Algonaiman,

Almutairi,

Al Zhrani

et al. 2023

Biomolecules

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Pregnancy and lactation are critical periods for human well-being and are sensitive windows for pollutant exposure. Bisphenol A (BPA) is well demonstrated as a toxicant and has been replaced in the plastic industry with other bisphenol analogs that share similarities in structure and characteristics, most commonly Bisphenol S (BPS) and Bisphenol F (BPF). Maternal exposure to BPS or BPF can result in their accumulation in the fetal compartment, leading to chronic exposure and potentially limiting normal fetal growth and development. This review summarizes considerable findings of epidemiological or experimental studies reporting associations between BPS or BPF and impaired fetal growth and development. Briefly, the available findings indicate that exposure to the two bisphenol analogs during pregnancy and lactation can result in multiple disturbances in the offspring, including fetal growth restrictions, neurological dysfunctions, and metabolic disorders with the potential to persist throughout childhood. The occurrence of premature births may also be attributed to exposure to the two bisphenols. The possible mechanisms of actions by which the two bisphenols can induce such effects can be attributed to a complex of interactions between the physiological mechanisms, including impaired placental functioning and development, dysregulation of gene expression, altered hormonal balance, and disturbances in immune responses as well as induced inflammations and oxidative stress. In conclusion, the available evidence suggests that BPS and BPF have a toxic potential in a compartment level to BPA. Future research is needed to provide more intensive information; long-term studies and epidemiological research, including a wide scale of populations with different settings, are recommended. Public awareness regarding the safety of BPA-free products should also be enhanced, with particular emphasis on educating individuals responsible for the well-being of children.

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Section: Effects On Cognitive Functions and Psychomotor Skillsmentioning

confidence: 95%

Effects of Prenatal Exposure to Bisphenol A Substitutes, Bisphenol S and Bisphenol F, on Offspring’s Health: Evidence from Epidemiological and Experimental Studies

Algonaiman,

Almutairi,

Al Zhrani

et al. 2023

Biomolecules

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“…In our previous research [ 3 , 17 – 19 ], we used ex vivo approaches, cell-based experiments, and animal models to characterize monoamine homeostasis at the maternal-fetal interface. In the perfused rat placenta, we demonstrated that OCT3 effectively removes monoamines from fetal circulation for subsequent metabolism in trophoblast cells [ 3 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of a human placental clearance system to regulate serotonin levels in the fetoplacental unit

Staud,

Pan,

Karahoda

et al. 2023

Reprod Biol Endocrinol

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Background Serotonin (5-HT) is a biogenic monoamine with diverse functions in multiple human organs and tissues. During pregnancy, tightly regulated levels of 5-HT in the fetoplacental unit are critical for proper placental functions, fetal development, and programming. Despite being a non-neuronal organ, the placenta expresses a suite of homeostatic proteins, membrane transporters and metabolizing enzymes, to regulate monoamine levels. We hypothesized that placental 5-HT clearance is important for maintaining 5-HT levels in the fetoplacental unit. We therefore investigated placental 5-HT uptake from the umbilical circulation at physiological and supraphysiological levels as well as placental metabolism of 5-HT to 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA efflux from trophoblast cells. Methods We employed a systematic approach using advanced organ-, tissue-, and cellular-level models of the human placenta to investigate the transport and metabolism of 5-HT in the fetoplacental unit. Human placentas from uncomplicated term pregnancies were used for perfusion studies, culturing explants, and isolating primary trophoblast cells. Results Using the dually perfused placenta, we observed a high and concentration-dependent placental extraction of 5-HT from the fetal circulation. Subsequently, within the placenta, 5-HT was metabolized to 5-hydroxyindoleacetic acid (5-HIAA), which was then unidirectionally excreted to the maternal circulation. In the explant cultures and primary trophoblast cells, we show concentration- and inhibitor-dependent 5-HT uptake and metabolism and subsequent 5-HIAA release into the media. Droplet digital PCR revealed that the dominant gene in all models was MAO-A, supporting the crucial role of 5-HT metabolism in placental 5-HT clearance. Conclusions Taken together, we present transcriptional and functional evidence that the human placenta has an efficient 5-HT clearance system involving (1) removal of 5-HT from the fetal circulation by OCT3, (2) metabolism to 5-HIAA by MAO-A, and (3) selective 5-HIAA excretion to the maternal circulation via the MRP2 transporter. This synchronized mechanism is critical for regulating 5-HT in the fetoplacental unit; however, it can be compromised by external insults such as antidepressant drugs.

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Molecular pathways in placental-fetal development and disruption

Adibi,

Zhao,

Koistinen

et al. 2024

Molecular and Cellular Endocrinology

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Functional characterization of dopamine and norepinephrine transport across the apical and basal plasma membranes of the human placental syncytiotrophoblast

Cited by 7 publications

References 57 publications

Effects of Prenatal Exposure to Bisphenol A Substitutes, Bisphenol S and Bisphenol F, on Offspring’s Health: Evidence from Epidemiological and Experimental Studies

Effects of Prenatal Exposure to Bisphenol A Substitutes, Bisphenol S and Bisphenol F, on Offspring’s Health: Evidence from Epidemiological and Experimental Studies

Characterization of a human placental clearance system to regulate serotonin levels in the fetoplacental unit

Molecular pathways in placental-fetal development and disruption

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