Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA343171 | ENA |
REPOSITORIES: ENA
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Project description:GnRH neurons are fundamental for reproduction in all vertebrates ultimately integrating all reproductive inputs. The inaccessibility of human GnRH-neurons has been a major impediment to studying the central control of reproduction and its disorders. Here, we report the efficient generation of kisspeptin responsive GnRH-secreting neurons by directed differentiation of human Pluripotent Stem Cells. The protocol involves the generation of intermediate Neural Progenitor Cells (NPCs) through long-term Bone morphogenetic protein 4 inhibition followed by terminal specification of these NPCs in a media containing FGF8 and a NOTCH inhibition. The resulting GnRH expressing and secreting neurons display a neuroendocrine gene expression pattern and present spontaneous calcium transients that can be stimulated by kisspeptin. These in vitro generated GnRH expressing cells provide a new resource for studying the molecular mechanisms underlying the development and function of GnRH neurons.
2016-09-17 | GSE86990 | GEO
Project description:Fertility critically depends on the gonadotropin-releasing hormone (GnRH) pulse generator, a neural construct comprised of hypothalamic neurons coexpressing kisspeptin, neurokoinin-B and dynorphin. Here, using mathematical modeling and in vivo optogenetics we reveal for the first time how this neural construct initiates and sustains the appropriate ultradian frequency essential for reproduction. Prompted by mathematical modeling, we show experimentally using female estrous mice that robust pulsatile release of luteinizing hormone, a proxy for GnRH, emerges abruptly as we increase the basal activity of the neuronal network using continuous low-frequency optogenetic stimulation. Further increase in basal activity markedly increases pulse frequency and eventually leads to pulse termination. Additional model predictions that pulsatile dynamics emerge from nonlinear positive and negative feedback interactions mediated through neurokinin-B and dynorphin signaling respectively are confirmed neuropharmacologically. Our results shed light on the long-elusive GnRH pulse generator offering new horizons for reproductive health and wellbeing.SIGNIFICANCE STATEMENT The gonadotropin-releasing hormone (GnRH) pulse generator controls the pulsatile secretion of the gonadotropic hormones LH and FSH and is critical for fertility. The hypothalamic arcuate kisspeptin neurons are thought to represent the GnRH pulse generator, since their oscillatory activity is coincident with LH pulses in the blood; a proxy for GnRH pulses. However, the mechanisms underlying GnRH pulse generation remain elusive. We developed a mathematical model of the kisspeptin neuronal network and confirmed its predictions experimentally, showing how LH secretion is frequency-modulated as we increase the basal activity of the arcuate kisspeptin neurons in vivo using continuous optogenetic stimulation. Our model provides a quantitative framework for understanding the reproductive neuroendocrine system and opens new horizons for fertility regulation
Model is encoded by Johannes and submitted to BioModels by Ahmad Zyoud.
2024-09-02 | BIOMD0000000931 | BioModels
Project description:Hypothalamic gonadotropin-releasing hormone (GnRH) neurons lays the foundation for human development and reproduction, however, the critical cell populations and the entangled mechanisms underlying the development of human GnRH neurons remain poorly understood. Here, by utilizing our established human pluripotent stem cells-derived GnRH neuron model, we decoded the cellular heterogeneity and differentiation trajectories at the single-cell level. We found that a glutamatergic neuron population, which generated together with GnRH neurons, showed similar transcriptomic properties with olfactory sensory neuron and provided the migratory path for GnRH neurons. Through trajectory analysis, we identified a specific gene module activated along the GnRH neuron differentiation lineage, and we examined one of the transcription factors, DLX5, expression in human fetal GnRH neurons. Furthermore, we found that Wnt inhibition could increase DLX5 expression, and improve the GnRH neuron differentiation efficiency through promoting neurogenesis and switching the differentiation fates of neural progenitors into glutamatergic neurons/GnRH neurons. Our research comprehensively reveals the dynamic cell population transition and gene regulatory network during GnRH neuron differentiation.
2022-10-04 | GSE212901 | GEO
Project description:Stress is defined as a systemic nonspecific adaptive response to the stimulations from internal and external environment or psychological factors through coordinating series of complex systems, like nervous system, immune system and respiratory system. While it is well known that stress have profound negative effects on reproductive function, the mechanism of reproductive dysfunction is still far from perfect. Kisspeptin, which are known for regulating GnRH synthesis and secretion, affect the initiation of puberty and reproduction, have been shown to express glucocorticoid receptors(GR),and both acute and chronic stress significantly inhibit Kisspeptin expression. So, this study speculated that Kisspeptin might participate in the process of reproductive regulation during stress. However, when constructed stress models of GT1-7 cells(Derived from mouse hypothalamic neurons, could not only transcribe endogenous GnRH mRNA and release GnRH when depolarization, but also express Kisspeptin, G protein-coupled receptors) with DEX and tried to analyze the specific mechanism of stress inhibited Kisspeptin expression, opposite results(Dex improved Kisspeptin expression of GT1-7 cells) were obtained. Based on the neuroimmune system hypothesis of stress, this study speculated that the direct reason of stress inhibited Kisspeptin expression might be stress-induced inflammatory response rather than stress-elevated GC. Even so, the transcription of Il-1β decreased in BV-2 cells(Derived from mouse Microglia) after treated with DEX. Due to the proximity of Kisspeptin neurons and Microgila in arcuate nucleus(ARC) of hypothalamus, it is speculated that there maight be interaction between them. So, this study co-cultured GT1-7 cells and BV-2 cells, and found transcription of Kiss1 decreased and Il-1β increased. Decreased Kisspeptin expression due to inflammation of BV-2 cells and inflammation of BV-2 cells must due to changes of certain substances or molecules in GT1-7 cells after treated with DEX. To further explore the possible mechanism, this study used the highly sensitive miRNAs array to screen miRNAs which not only changed significantly in GT1-7 cells after treated with DEX but also associated with inflammation. Finally, 10 miRNAs obtained and further confirmed mmu-miR-146a-5P could inhibited the LPS-induced BV-2 cells inflammation, M1 polarization and apoptosis.
2025-12-31 | GSE230086 | GEO
Project description:Syncytiotrophoblast generation from human pluripotent stem cells
| PRJNA294733 | ENA
Project description:Kisspeptin-expressing neurons in the rostral periventricular region of the third ventricle (RP3V) play an essential role in female reproduction. However, adult male mice were reported to have very few Kisspeptin-expressing neurons in the RP3V compared to females. This led to the hypothesis that Kiss1 RP3V neurons are responsible for the ability of females, but not males, to generate a surge of LH, triggering ovulation and steroid synthesis in the female. Using mouse genetics and cell type-specific gene expression analysis, we show that male mice harbor almost as many Kiss1 RP3V neurons as the female and that gene expression in these neurons is very similar. Specific activation of male Kiss1 RP3V neurons expressing viral-encoded hM3Dq caused a surge in serum testosterone levels. These results demonstrate that Kiss1 RP3V neurons are present in the adult male and fully capable of regulating the hypothalamic/pituitary/gonadal axis. We suggest that these neurons may continue to play a role in reproductive behavior in adult male mice.
2021-06-01 | GSE165015 | GEO
Project description:Characterisation of induced motor neurons (iMN) generated from human induced pluripotent stem cells (hiPSC, hPSCreg name BIHi005-A) using doxycycline inducible expression of Ngn2, Isl1 and Lhx3. While this method of iMN generation has been described before (REF: doi.org/10.1002/cpcb.51), no extensive characterisation of the transcriptome and proteome throughout the differentiation process or of the mature neurons has been undertaken so far.
2025-11-24 | PXD031066 | Pride
Project description:Generation of pluripotent stem cells from adult human testis
| PRJNA106567 | ENA
Project description:Reproductive sterilization via surgical gonadectomy is strongly advocated to help manage animal populations, especially domesticated pets, and to prevent reproductive diseases. The present study explored the feasibility of using a single-injection method for inducing sterility in female animals as an alternative to surgical sterilization. The idea was based upon our recent finding that repetitive daily injection of estrogen into neonatal rats disrupted hypothalamic expression of Kisspeptin, the neuropeptide that triggers and regulates pulsatile secretion of GnRH in the hypothalamus. In this study, neonatal female rats were dosed with estradiol benzoate (EB) by daily injection for 11 days or subcutaneously implanted with an EB-containing Silastic capsule designed to release EB over a 2- to 3-week period. Rats treated by either method did not exhibit estrous cyclicity, were anovulatory, and became infertile. The EB-treated rats had fewer Kisspeptin neurons in their hypothalami, but their GnRH-LH axis retained responsiveness to Kisspeptin stimulation. To simplify usage, an injectable EB carrier was developed in the forms of biodegradable microspheres or pellets with pharmacokinetics comparable to the EB-containing Silastic capsule. A single injection of EB microspheres (300 µg EB) to neonatal rats made them sterile and female beagles implanted with an EB pellet at a neonatal age had lower KISS expression in their hypothalami. No concerning health impact other than infertility was observed in animals that received EB treatment at a neonatal age. Taken together, this study shows that neonatal EB administration could be developed as a non-surgical animal sterilization method.
2023-06-21 | GSE221002 | GEO