Comparative assessment of toxic responses in 3D embryoid body differentiation model and mouse early embryos treated with 5-hydroxytryptophan

Gordeeva, O. F.; Gordeev, Andrey

doi:10.1007/s00204-020-02909-w

Cited by 5 publications

(3 citation statements)

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“…The limitation of diffusion of small molecules and proteins in differentiating EBs occurs after forming tight junctions and a powerful basement membrane and contributes to the further EB patterning. Interestingly, the multilayered ExEn can partially compensate for the barrier function of the trophectoderm, which provides selective transport of active substances and drugs to the embryo ( Marikawa and Alarcon, 2012 ; Eliesen et al, 2021 ; Gordeeva and Gordeev, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

“…To analyze the proliferative cell domain, the numbers of EdU-labeled and the total Hoechst-stained nuclei in the EBs were counted using the 2D Automated Cell Counter tool in ImageJ software ( https://imagej.nih.gov/ij/plugins/cell-counter.html ) for confocal stacks, as previously described ( Gordeeva and Gordeev, 2021 ). The cell counts were based on the object-level identification of Hoechst- and EdU-stained nuclei in each plane of confocal z-stack, which were counted in two separate channels.…”

Section: Methodsmentioning

confidence: 99%

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Archetypal Architecture Construction, Patterning, and Scaling Invariance in a 3D Embryoid Body Differentiation Model

Gordeeva

Gordeev

Erokhov

2022

Front. Cell Dev. Biol.

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Self-organized patterning and architecture construction studying is a priority goal for fundamental developmental and stem cell biology. To study the spatiotemporal patterning of pluripotent stem cells of different origins, we developed a three-dimensional embryoid body (EB) differentiation model quantifying volumetric parameters and investigated how the EB architecture formation, patterning, and scaling depend on the proliferation, cavitation, and differentiation dynamics, external environmental factors, and cell numbers. We identified three similar spatiotemporal patterns in the EB architectures, regardless of cell origin, which constitute the EB archetype and mimick the pre-gastrulation embryonic patterns. We found that the EB patterning depends strongly on cellular positional information, culture media factor/morphogen content, and free diffusion from the external environment and between EB cell layers. However, the EB archetype formation is independent of the EB size and initial cell numbers forming EBs; therefore, it is capable of scaling invariance and patterning regulation. Our findings indicate that the underlying principles of reaction-diffusion and positional information concepts can serve as the basis for EB architecture construction, patterning, and scaling. Thus, the 3D EB differentiation model represents a highly reproducible and reliable platform for experimental and theoretical research on developmental and stem cell biology issues.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Archetypal Architecture Construction, Patterning, and Scaling Invariance in a 3D Embryoid Body Differentiation Model

Gordeeva

Gordeev

Erokhov

2022

Front. Cell Dev. Biol.

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“…Insights from animal studies suggest that maternal 5-HTP can directly inhibit fetal growth by passing into the fetal circulation. These animal studies showed that 5-HTP can induce developmental arrest, inhibit growth, and increase cell death ( Gordeeva and Gordeev, 2021 ; Gordeeva and Safandeev, 2021 ). In humans, there is increasing evidence that initially nutrition of the embryo is histiotrophic, with secretion of nutrients by uterine glands into the intervillous space, which are taken up by the trophoblast ( Burton et al , 2001 ).…”

Section: Discussionmentioning

confidence: 99%

First trimester maternal tryptophan metabolism and embryonic and fetal growth: the Rotterdam Periconceptional Cohort (Predict Study)

van Zundert,

van Egmond,

van Rossem

et al. 2024

Human Reproduction

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STUDY QUESTION What is the association between first trimester maternal tryptophan (TRP) metabolites and embryonic and fetal growth? SUMMARY ANSWER Higher 5-hydroxytryptophan (5-HTP) concentrations are associated with reduced embryonic growth and fetal growth and with an increased risk of small-for-gestational age (SGA), while higher kynurenine (KYN) concentrations are associated with a reduced risk of SGA. WHAT IS KNOWN ALREADY The maternal TRP metabolism is involved in many critical processes for embryonic and fetal growth, including immune modulation and regulation of vascular tone. Disturbances in TRP metabolism are associated with adverse maternal and fetal outcomes. STUDY DESIGN, SIZE, DURATION This study was embedded within the Rotterdam Periconceptional Cohort (Predict Study), an ongoing prospective observational cohort conducted at a tertiary hospital from November 2010 onwards. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 1115 women were included before 11 weeks of gestation between November 2010 and December 2020. Maternal serum samples were collected between 7 and 11 weeks of gestation, and TRP metabolites (TRP, KYN, 5-HTP, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid) were determined using a validated liquid chromatography (tandem) mass spectrometry method. Serial 3D ultrasound scans were performed at 7, 9, and 11 weeks of gestation to accurately assess features of embryonic growth, including crown–rump length (CRL) and embryonic volume (EV) offline using virtual reality systems. Fetal growth parameters were retrieved from medical records and standardized according to Dutch reference curves. Mixed models were used to assess associations between maternal TRP metabolites and CRL and EV trajectories. Linear and logistic regression models were utilized to investigate associations with estimated fetal weight (EFW) and birthweight, and with SGA, respectively. All analyses were adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE Maternal 5-HTP concentrations and the maternal 5-HTP/TRP ratio were inversely associated with embryonic growth (5-HTP, √CRL: β = –0.015, 95% CI = –0.028 to –0.001; 5-HTP 3√EV: β = –0.009, 95% CI = –0.016 to –0.003). An increased maternal 5-HTP/TRP ratio was also associated with lower EFW and birthweight, and with an increased risk of SGA (odds ratio (OR) = 1.006, 95% CI = 1.00–1.013). In contrast, higher maternal KYN concentrations were associated with a reduced risk of SGA in the unadjusted models (OR = 0.548, 95% CI = 0.320–0.921). LIMITATIONS, REASONS FOR CAUTION Residual confounding cannot be ruled out because of the observational design of this study. Moreover, this study was conducted in a single tertiary hospital, which assures high internal validity but may limit external validity. WIDER IMPLICATIONS OF THE FINDINGS The novel finding that maternal 5-HTP concentrations are associated with a smaller embryo and fetus implies that disturbances of the maternal serotonin pathway in the first trimester of pregnancy are potentially involved in the pathophysiology of fetal growth restriction. The association between higher maternal KYN concentrations and a reduced risk of SGA substantiate the evidence that the KYN pathway has an important role in fetal growth. More research is needed to delve deeper into the potential role of the maternal TRP metabolism during the periconception period and pregnancy outcome for mother and offspring. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the Department of Obstetrics and Gynecology and the Department of Clinical Chemistry of the Erasmus MC, University Medical Center, Rotterdam, the Netherlands. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A.

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High Content Image Analysis of Spatiotemporal Proliferation and Differentiation Patterns in 3D Embryoid Body Differentiation Model

Gordeeva

2021

Embryonic Stem Cell Protocols

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Comparative assessment of toxic responses in 3D embryoid body differentiation model and mouse early embryos treated with 5-hydroxytryptophan

Cited by 5 publications

References 41 publications

Archetypal Architecture Construction, Patterning, and Scaling Invariance in a 3D Embryoid Body Differentiation Model

Archetypal Architecture Construction, Patterning, and Scaling Invariance in a 3D Embryoid Body Differentiation Model

First trimester maternal tryptophan metabolism and embryonic and fetal growth: the Rotterdam Periconceptional Cohort (Predict Study)

High Content Image Analysis of Spatiotemporal Proliferation and Differentiation Patterns in 3D Embryoid Body Differentiation Model

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