Related Experiment Video

Updated: May 21, 2026

Human Primary Trophoblast Cell Culture Model to Study the Protective Effects of Melatonin Against Hypoxia/reoxygenation-induced Disruption
12:02

Human Primary Trophoblast Cell Culture Model to Study the Protective Effects of Melatonin Against Hypoxia/reoxygenation-induced Disruption

Published on: July 30, 2016

Caffeine reduces 11β-hydroxysteroid dehydrogenase type 2 expression in human trophoblast cells through the adenosine

Saina Sharmin1, Haiyan Guan, Andrew Scott Williams

  • 1Children's Health Research Institute, Department of Obstetrics, The University of Western Ontario, London, Ontario, Canada.

Plos One
|June 16, 2012
PubMed

Insights

Maternal caffeine intake may harm fetal growth by reducing placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity. This effect is mediated by the adenosine A(2B) receptor, highlighting a new pathway for caffeine

Area of Science:

  • Reproductive Biology
  • Molecular Endocrinology
  • Developmental Toxicology

Background:

  • Maternal caffeine consumption is linked to reduced fetal growth.
  • Decreased placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is associated with fetal growth restriction.
  • The molecular mechanisms linking caffeine to fetal growth restriction are largely unknown.

Purpose of the Study:

  • To investigate if caffeine and its metabolite paraxanthine inhibit fetal growth by downregulating placental 11β-HSD2.
  • To explore the molecular pathways involved in caffeine's effect on placental 11β-HSD2.

Main Methods:

  • Primary human trophoblast cells were used as an in vitro model.
  • Effects of caffeine and paraxanthine on 11β-HSD2 activity, protein, and mRNA were measured.
  • Adenosine A(2B) receptor was targeted using siRNA, and forskolin was used to modulate cAMP levels.

Main Results:

  • Both caffeine and paraxanthine reduced placental 11β-HSD2 activity, protein, and mRNA in a dose-dependent manner.
  • Inhibition of 11β-HSD2 by caffeine and paraxanthine was dependent on the adenosine A(2B) receptor.
  • Forskolin treatment reversed the inhibitory effects, indicating a role for cyclic AMP (cAMP) signaling.

Conclusions:

  • Placental 11β-HSD2 is a novel molecular target through which caffeine may adversely affect fetal growth.
  • Adenosine A(2B) receptor signaling plays a crucial role in regulating placental 11β-HSD2 activity.
  • Caffeine's impact on placental 11β-HSD2 and fetal development involves modulation of intracellular cAMP levels.

More Related Videos

Trophoblast Cell Recovery from Angiogenesis-Tube Formation Assay for Differentiation Marker Expression Analysis05:30

Trophoblast Cell Recovery from Angiogenesis-Tube Formation Assay for Differentiation Marker Expression Analysis

Published on: November 8, 2024

Caffeine Extraction, Enzymatic Activity and Gene Expression of Caffeine Synthase from Plant Cell Suspensions09:11

Caffeine Extraction, Enzymatic Activity and Gene Expression of Caffeine Synthase from Plant Cell Suspensions

Published on: October 2, 2018

Related Concept Videos

Adrenergic Receptors: β Subtype01:26

Adrenergic Receptors: β Subtype

β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
Isoprenaline > Adrenaline > Noradrenaline
Neurotransmitter binding to these receptors causes activation of adenylyl cyclase resulting in increased concentrations of cAMP and modulation of calcium ion channels within the cell. They are further classified into β1, β2, and β3 subtypes.
β1-adrenoceptors: β1-adrenoceptors have equal affinities for...
Adrenergic Antagonists: ɑ and β-Receptor Blockers01:31

Adrenergic Antagonists: ɑ and β-Receptor Blockers

Third-generation β-blockers, such as labetalol and carvedilol, represent a significant advancement in managing cardiovascular conditions. Unlike conventional β-blockers, which can induce peripheral vasoconstriction, third-generation drugs block α1 adrenoceptors. This promotes vasodilation through several mechanisms, such as increased nitric oxide production, inhibition of calcium ion entry, opening of potassium ion channels, and antioxidant action. Labetalol, for instance, is clinically...
Teratogenicity01:07

Teratogenicity

The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Target Cell Response to Hormones01:22

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Drugs Affecting Neurotransmitter Synthesis01:29

Drugs Affecting Neurotransmitter Synthesis

Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase, which converts...