A Mathematical Model for the Estimation of Human Embryonic and Fetal Age

Evtouchenko, L.; Studer, Lorenz; Spenger, Christian; Dreher, E.; Seiler, Rolf W.

doi:10.1177/096368979600500404

Cited by 53 publications

(8 citation statements)

References 18 publications

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“…Human fetal tissue was collected from routine elective termination of pregnancy, in full compliance with guidelines established by the UK Department of Health and local ethics committees. The post‐conception age of the embryonic material was 10 weeks (± 2 days), as determined by measurement of identifiable fetal parts (Evtouchenko et al. 1996).…”

Section: Methodsmentioning

confidence: 99%

The survival of neural precursor cell grafts is influenced by in vitro expansion

et al. 2005

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Embryonic neural precursor cells (ENPs) provide a potential alternative for transplantation in neurodegenerative diseases, as they can be expanded in culture, avoiding many of the practical obstacles that limit the application of transplanting primary neurones. However, grafts of ENPs into animal models show variable survival and limited differentiation into neurones. The effect of expansion time on their ability to survive and differentiate may be an important factor in this and has not been examined directly. In these experiments, murine and human ENPs were expanded for short (4 weeks) and long (20 weeks) periods before transplantation into the adult rat striatum.Whereas grafts of both short-and long-term expanded human ENPs survived for 4 weeks following transplantation, by 20 weeks all long-term expanded grafts had disappeared. Murine ENPs behaved similarly: only grafts of short-term expanded ENPs survived at 12 weeks following transplantation. RT-PCR analysis of ENP cultures after 4and 20 weeks of expansion demonstrated changes in expression of a number of different groups of genes. We conclude that long-term expansion of ENPs profoundly impairs their ability to survive long-term after transplantation into the adult brain. This has implications for the potential use of these cells for neural transplantation strategies.

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Section: Methodsmentioning

confidence: 99%

The survival of neural precursor cell grafts is influenced by in vitro expansion

et al. 2005

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“…Fetal material was kept at 4°C immediately after termination of pregnancy and during transport to the laboratory. Fetal age was determined by scanning crown-rump length and by evaluation of foot length [18]. Fetal adrenal tissue was dissected in ice-cold PBS and immediately setup in ex vivo cultures.…”

Section: Tissue Collectionmentioning

confidence: 99%

The effects of selected inhibitors on human fetal adrenal steroidogenesis differs under basal and ACTH-stimulated conditions

Melau

Riis

Nielsen

et al. 2021

BMC Med

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Background Disordered fetal adrenal steroidogenesis can cause marked clinical effects including virilization of female fetuses. In postnatal life, adrenal disorders can be life-threatening due to the risk of adrenal crisis and must be carefully managed. However, testing explicit adrenal steroidogenic inhibitory effects of therapeutic drugs is challenging due to species-specific characteristics, and particularly the impact of adrenocorticotropic hormone (ACTH) stimulation on drugs targeting steroidogenesis has not previously been examined in human adrenal tissue. Therefore, this study aimed to examine the effects of selected steroidogenic inhibitors on human fetal adrenal (HFA) steroid hormone production under basal and ACTH-stimulated conditions. Methods This study used an established HFA ex vivo culture model to examine treatment effects in 78 adrenals from 50 human fetuses (gestational weeks 8–12). Inhibitors were selected to affect enzymes critical for different steps in classic adrenal steroidogenic pathways, including CYP17A1 (Abiraterone acetate), CYP11B1/2 (Osilodrostat), and a suggested CYP21A2 inhibitor (Efavirenz). Treatment effects were examined under basal and ACTH-stimulated conditions in tissue from the same fetus and determined by quantifying the secretion of adrenal steroids in the culture media using liquid chromatography-tandem mass spectrometry. Statistical analysis was performed on ln-transformed data using one-way ANOVA for repeated measures followed by Tukey’s multiple comparisons test. Results Treatment with Abiraterone acetate and Osilodrostat resulted in potent inhibition of CYP17A1 and CYP11B1/2, respectively, while treatment with Efavirenz reduced testosterone secretion under basal conditions. ACTH-stimulation affected the inhibitory effects of all investigated drugs. Thus, treatment effects of Abiraterone acetate were more pronounced under stimulated conditions, while Efavirenz treatment caused a non-specific inhibition on steroidogenesis. ACTH-stimulation prevented the Osilodrostat-mediated CYP11B1 inhibition observed under basal conditions. Conclusions Our results show that the effects of steroidogenic inhibitors differ under basal and ACTH-stimulated conditions in the HFA ex vivo culture model. This could suggest that in vivo effects of therapeutic drugs targeting steroidogenesis may vary in conditions where patients have suppressed or high ACTH levels, respectively. This study further demonstrates that ex vivo cultured HFAs can be used to evaluate steroidogenic inhibitors and thereby provide novel information about the local effects of existing and emerging drugs that targets steroidogenesis.

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“…Human embryo spinal cords were harvested from material obtained following legally induced terminations of pregnancy (first trimester of pregnancy) from the Department of Obstetrics and Gynecology at the Antoine Béclère Hospital (Clamart, France). Fetal age was calculated by measuring the length of limbs and feet according to a developed mathematical model 75 and none of the induced abortions were performed for reasons of fetal abnormality. Tissues were collected in absence of compensation, with written informed consent specifying the purpose of the research, in accordance with legal procedures agreed by the French Biomedicine Agency, Agence de la Biomédecine (authorized project number PFS12-002).…”

Section: Methodsmentioning

confidence: 99%

Single-cell transcriptomic analysis reveals diversity within mammalian spinal motor neurons

et al. 2023

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Spinal motor neurons (MNs) integrate sensory stimuli and brain commands to generate movements. In vertebrates, the molecular identities of the cardinal MN types such as those innervating limb versus trunk muscles are well elucidated. Yet the identities of finer subtypes within these cell populations that innervate individual muscle groups remain enigmatic. Here we investigate heterogeneity in mouse MNs using single-cell transcriptomics. Among limb-innervating MNs, we reveal a diverse neuropeptide code for delineating putative motor pool identities. Additionally, we uncover that axial MNs are subdivided into three molecularly distinct subtypes, defined by mediolaterally-biased Satb2, Nr2f2 or Bcl11b expression patterns with different axon guidance signatures. These three subtypes are present in chicken and human embryos, suggesting a conserved axial MN expression pattern across higher vertebrates. Overall, our study provides a molecular resource of spinal MN types and paves the way towards deciphering how neuronal subtypes evolved to accommodate vertebrate motor behaviors.

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A Mathematical Model for the Estimation of Human Embryonic and Fetal Age

Cited by 53 publications

References 18 publications

The survival of neural precursor cell grafts is influenced by in vitro expansion

The survival of neural precursor cell grafts is influenced by in vitro expansion

The effects of selected inhibitors on human fetal adrenal steroidogenesis differs under basal and ACTH-stimulated conditions

Single-cell transcriptomic analysis reveals diversity within mammalian spinal motor neurons

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