搜索结果：Developmental biology

Cancer is increasingly conceptualized as a disease of distorted human development, where oncogenic events trigger developmental reprogramming by subverting physiological lineage programs. Conventional cancer models often fail to capture this early transition, as they primarily reflect end-stage tumors or nonhuman biology. Human pluripotent stem cells (hPSCs) circumvent these limitations by enabling the reconstruction of oncogenic events within precisely defined human developmental trajectories. In this review, we examine emerging principles of lineage bias and differentiation arrest revealed by hPSC-derived models across brain, retinal, and myeloid malignancies, as well as hereditary cancer predispositions. Crucially, we discuss how these models reveal therapeutic windows linked to defined developmental states to reverse lineage hijacking, translating developmental insights into pharmacological strategies for early cancer interception.

Antonio García-Bellido was a pioneer of developmental biology in Spain who had the rare ability to see beyond the trees and grasp not just the forest, but entire landscapes. Intellectually and personally, he was indefatigable, uncompromising, and wholly committed to science. He led his trainees by example in his unflagging demands on honoring the data above all else. Antonio discovered the existence of "developmental compartments" in the wing of Drosophila and proposed that these territories corresponded to the realm of action of homeotic genes. He was a fierce defender of hypotheses that he thought best explained available data but did not cling blindly to ideas when they no longer served to understand the phenomena at hand. With his distinctive style he founded a successful school of Drosophila developmental geneticists that will sorely miss his unparalleled passion for science.

The retinal development of elasmobranchs, the subclass comprising sharks, skates, and rays, remains poorly understood. This group is diverse in retinal phenotype, with many sharks and rays possessing rods together with one or more cone tyes. In contrast, the little skate (Leucoraja erinacea) has only a single rod photoreceptor type, which has been reported to exhibit some physiological and anatomical properties associated with cones. To investigate how this unusual photoreceptor system develops, we first identified an embryonic stage of early photoreceptor formation based on otx2 expression. We then developed a retinal electroporation approach to test whether a onecut1-dependent cone-associated reporter could be activated in the embryonic skate retina. Activation of this reporter was not detected, indicating that the corresponding enhancer is not robustly active under the conditions tested. To assess developmental changes in gene expression, we generated bulk RNA-seq datasets from embryonic, hatchling, and adult retinas. These analyses showed strong embryonic expression of onecut1, increasing expression of rod-associated genes through development, and pseudogenization or loss of multiple cone-enriched genes. We further identified a developmentally regulated onecut1 splice isoform containing an additional 48 amino acid sequence between the CUT and homeodomain DNA-binding domains. This spacer-containing isoform, termed LSOC1X2, was most abundant in the embryonic retina. To test whether LSOC1X2 retained regulatory activity, we assayed it in a mouse retinal reporter system. Both skate Onecut1 isoforms activated the ThrbCRM1 reporter in this heterologous context. Together, these findings identify a novel, developmentally regulated retinal onecut1 isoform in the little skate and establish it as a candidate regulator for future studies of photoreceptor development in this species and its elasmobranch relatives.

Cell states alone rarely resolve woody developmental continua. To recover developmental continuity, Wei et al. integrated single-cell, single-nucleus, and spatial transcriptomics in poplar xylem. Their study highlights a broader principle for forestry: cell-resolved atlases become explanatory when interpreted in an anatomical context and linked to developmental continuity and experimental validation.

The toxicity of nanoplastics (NPs) and plastic additives such as phthalates, recognized endocrine-disrupting chemicals, remains insufficiently understood, particularly regarding their combined effects on male reproductive health across the lifespan. Since these contaminants can cross biological barriers, including the placenta, this study, grounded in the developmental origins of health and disease (DOHaD) concept, evaluated the effects of gestational and lactational exposure to NPs and a phthalate mixture (PM) on testicular development and function in male offspring. Pregnant SD rats were allocated to six groups: control (CTRL); T1 (20μg/kg/day PM); T2 (200mg/kg/day PM); T3 (NPs: 1mg/kg/day,100nm); T4 (20μg/kg/day PM+NPs); and T5 (200mg/kg/day PM+NPs). Animals were exposed orally from gestational day 10 to postnatal day (PND)21. Male offspring were euthanized at PND22 (prepuberty) and PND120 (adulthood). At PND22, increased apoptosis in pachytene spermatocytes was observed in the T5 group compared with the CTRL, along with altered gene expression, including increased Amh (T4 vs.T1) and Srd5a1 (T1-T4 vs.CTRL) and reduced Ar expression (T3 vs.CTRL). At PND120, the exposure decreased seminiferous tubule diameter (T2), epithelial height (T1-T5), and numbers of Sertoli (T2-T5) and Leydig cells (T4 and T5) compared to the CTRL. Histopathological alterations were more incident in the T1, T3, T4, and T5 compared to the CTRL, and reduced Tjp1 expression in co-exposed animals suggested impairment of the blood-testis barrier. Redox analyses revealed age-dependent worsening of oxidative stress, particularly in co-exposure groups. Overall, gestational co-exposure to phthalates and NPs disrupts testicular morphology, gene regulation, and redox balance, indicating synergistic and persistent reproductive toxicity.

Human coronaviruses have been primarily associated with upper respiratory tract infections, yet cases of gastrointestinal symptoms in COVID-19 patients have highlighted their potential to cause systemic disease. Here, we detail the infection of intestinal epithelia by an endemic, low-pathogenic human coronavirus, human alphacoronavirus 229E, using patient-derived human intestinal enteroids (HIEs) from donors of various ages. Using fetal, pediatric, and adult HIEs, we investigated how physiologically relevant temperatures: 37 °C and 32 °C, reflecting gastrointestinal and upper-airway conditions, respectively, modulate epithelial responses and viral infection dynamics. We show that there is temperature-dependent transcriptional reprogramming, indicating strong temperature-dependent regulation of virus replication and epithelial responses. Among the seasonal coronaviruses tested, only HCoV-229E productively infects HIEs. At 32 °C, HCoV-229E replicates efficiently in enteroids from all donor ages and releases high titers of infectious progeny. In contrast, at 37 °C, productive replication is largely confined to fetal and a subset of pediatric tissues, revealing a developmental and temperature-sensitive restriction on infection. Confocal and flow cytometry analyses identify enterocytes as the primary target cells for HCoV-229E. Furthermore, we show that camostat, a serine protease inhibitor, significantly reduces HCoV-229E replication in HIEs, confirming a critical role for host serine protease activity. Collectively, these findings establish HIEs as a relevant model for HCoV-229E-host interactions and reveal temperature- and age-dependent determinants governing intestinal permissiveness to this seasonal coronavirus.

Aquaculture faces severe threats from bacterial disease outbreaks, creating an urgent need for safe, and sustainable alternatives to synthetic antibiotics and harmful chemicals. Alstonia scholaris (L.) R. Br. (Apocynaceae), widely recognized in traditional medicine for its therapeutic potential, has received limited attention in aquaculture. This study evaluated the antimicrobial potency of A. scholaris leaf extracts against key fish pathogens. The ethanolic extract showed promising broad-spectrum antibacterial potency and further bioassay-guided fractionation of it targeting Pseudomonas fluorescens led to putative identification of oleanolic acid as the principal bioactive constituent. The isolated compound exhibited broad-spectrum antibacterial activities against P. fluorescens, Streptococcus agalactiae, and Streptococcus iniae. Safety evaluation using zebrafish embryos demonstrated that the ethanolic extract caused no mortality at or below 125 µg/mL and was found non-teratogenic, while, the isolated compound exhibited no embryotoxicity up to 300 µg/mL concentration. This study reports the first identification of oleanolic acid from the ethanolic extract of A. scholaris leaves using bioassay-guided fractionation targeting P. fluorescens. These findings highlight the potential of the A. scholaris leaves ethanolic extract and its isolated active compound as safe, effective, and sustainable antimicrobial alternatives for bacterial disease management in aquaculture.

Understanding how stable developmental patterns emerge from gene regulatory networks remains a central problem in developmental biology. Here, we study how classical homeotic mutations reshape the epigenetic landscape of the floral gene regulatory network of Arabidopsis thaliana. We represent this landscape as an Epigenetic Forest: a collection of rooted in-arborescences induced by the state transition graph of a Boolean gene regulatory network, where each tree is the basin of attraction of a stable gene expression pattern associated with a floral or meristematic identity. We apply this framework to the wild-type network, three single homeotic mutants (ap1, pi, and ag), and three double mutants (ap3-pi, ag-pi, and ap1-ag). For each genotype, we quantify landscape organization using complementary descriptors of basin structure, convergence depth, fate diversity, dominance, inequality, and Jensen-Shannon divergence from wild type. The resulting landscapes reveal distinct modes of mutant-induced deformation. The ap1 mutant restricts fate accessibility and concentrates trajectories into dominant basins, whereas pi eliminates B-function-dependent identities while largely preserving global basin organization. In contrast, ag increases effective fate diversity despite the loss of reproductive identity, reflecting defective meristem termination and convergence to WUS-associated states. Double mutants exhibit non-additive deformation: ap3-pi is indistinguishable from pi across all reported descriptors, consistent with logical saturation of the AND-like B-function module, whereas ag-pi and ap1-ag produce distinct redistributions of fate accessibility. The framework recovers canonical floral identities and experimentally observed mutant phenotypes while treating the epigenetic landscape as a finite, computable object determined by regulatory logic. The framework thus provides a topology-based description of developmental robustness, epistasis, and mutant-induced landscape deformation.

Neonicotinoid insecticides, particularly imidacloprid, are widely used worldwide and have raised increasing concerns regarding their potential developmental neurotoxicity. However, data on the effects of imidacloprid exposure during early embryogenesis, especially on neural tube development and neurogenesis, remain limited. This study aimed to investigate the teratogenic effects of imidacloprid on neural tube development and neurogenesis in early embryonic stages using a chicken embryo model. 110 specific pathogen free (SPF) eggs were randomly assigned to a control group (saline) or four imidacloprid groups (0.1, 0.5, 1, and 5mg/kg), and all solutions were administered via sub-blastodermic injection. Embryos were evaluated at 48hours of incubation using morphometric assessments based on Hamburger-Hamilton staging. In addition, immunohistochemical and genetic analyses were performed. Imidacloprid exposure resulted in a dose-dependent increase in neural tube defects and developmental delay. Cysteine-dependent aspartate-directed protease-3 (Caspase-3) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity significantly increased, while proliferating cell nuclear antigen (PCNA) immunoreactivity decreased, indicating enhanced apoptosis and suppressed cellular proliferation. Gene expression analyses revealed significant dysregulation of neurogenesis- and proliferation-associated pathways, particularly involving fibroblast growth factor (FGF) signaling and cell cycle control. The results highlight the teratogenic potential of imidacloprid and underscore the importance of incorporating developmental neurotoxicity endpoints into pesticide risk assessment frameworks.

Amphibian metamorphosis is a dramatic thyroid hormone (TH) mediated process involving the transformation of aquatic larvae into more-terrestrial adults. But some salamanders, referred to as larval-form paedomorphs, completely or partially forgo metamorphosis, retaining their aquatic larval features and lifestyle into adulthood. This developmental pattern can be facultative or obligate and can manifest from lowering circulating TH and/or reducing TH-responsiveness of larval tissues. Obligate larval-form paedomorphs display varying degrees of responsiveness to TH-treatment; some species exhibit complete metamorphosis, while others show no overt transformation of larval-form tissues. Investigations of the latter species have shown that they have a functional TH-axis, but their tissues have become deregulated (decoupled) from ancestral TH-induced transformation. Obligate paedomorphosis is thought to evolve from facultative paedomorphosis through genetic assimilation followed by canalization. However, the developmental and physiological advantages of full TH-deregulation of larval-form tissues have not been discussed in detail. Since TH is intertwined with many processes such as stress-response, growth, and reproduction, we propose that directional selection for deregulation may allow TH and other interacting hormones to be utilized more effectively without compromising the larval-form. Furthermore, it is unclear whether facultative paedomorphosis is a necessary prerequisite step to becoming obligate. We propose alternative scenarios leading to TH-deregulation such as a rapid rate of directional selection after secondarily colonizing more divergent adaptive zones (e.g., aquifers), and relaxed selection from disusing ancestral TH-pathways for metamorphosis over many generations. Deregulating hormone pathways may be a more generalizable evolutionary phenomenon, reinforcing developmental evolution and perhaps generating novel signaling pathways.

Schwann cells (SCs), the predominant glial cell population in the peripheral nervous system (PNS), have undergone a paradigm shift from historically passive structural components of myelinated axons to active, multifunctional regulators of neural development, regeneration, and neuropathology. This review briefly outlines Schwann cell developmental origin as a biological backdrop, while centering on their inherent phenotypic plasticity and translational applications. Following peripheral nerve injury, SCs rapidly undergo context-dependent dedifferentiation and transcriptional reprogramming, acquiring a regenerative phenotype characterized by phagocytic activity, secretion of neurotrophic factors, and structural reorganization into Büngner bands. Notably, both endogenous and exogenously delivered SCs demonstrate capacity to migrate into lesioned central nervous system (CNS), including spinal cord injury sites, where they contribute to remyelination, modulation of glial scar formation, and partial restoration of electrophysiological connectivity and behavioral function. These attributes collectively establish SCs as phenotypically adaptable cellular mediators capable of facilitating neural repair across anatomically and functionally distinct compartments. To inform translational efforts, this review critically evaluates emerging strategies, including autologous cell transplantation and SC-derived exosomes, by appraising their mechanisms, limitations, and future perspectives. This review aims to deepen the mechanistic understanding of Schwann cell biology and provide a theoretical basis for the development of regenerative treatments for peripheral nerve injury and spinal cord injury.

When and how much plants grow under environmental constraints are fundamental questions in biology and increasingly important for predicting biomass production and carbon sequestration under climate change. While temperature and water availability directly regulate plant growth, the timing and rate of growth are also shaped by internal developmental programming, though this is rarely considered in predictions of tree growth responses to future climates. Here, we revisit a concept central to this internal programming-(in)determinacy. Focusing on woody plants, we define it as the extent to which annual shoot growth is deployed from preformed organs versus produced de novo during the current season. We argue that this trait is best understood as a continuum and that it can help explain contrasting growth responses in a changing climate. More determinate species concentrate growth within a narrow seasonal window, which may reduce exposure to late-season stress but also limit their ability to exploit longer growing seasons. More indeterminate species retain greater flexibility to extend or resume growth when conditions remain favourable, which may be advantageous under climate change, but this same flexibility may also increase exposure to frost, drought and incomplete tissue maturation. Because primary shoot growth also shapes canopy development and is linked to other growth processes, variation in (in)determinacy could help explain broader differences in whole-plant performance, carbon gain and species responses to climate change.

The thymus generates immunocompetent T cells, but its function declines with age. Thymic activity relies on proper differentiation of thymic epithelial cells (TECs), which establish unique niches for T-cell development. However, the molecular mechanisms governing the differentiation of functional cortical (c) and medullary (m) TEC subsets from common progenitors remain poorly understood. Using dual conditional knockout (dcKO) and lineage-tracing mouse models, we demonstrated that RNA-binding proteins ZFP36L1 and ZFP36L2 cooperatively maintain a functional TEC microenvironment. TEC-specific deletion of Zfp36l1 and Zfp36l2 in dcKO mouse models led to early-onset thymic hypoplasia and a marked reduction in TEC and thymocyte numbers. Mechanistically, single-cell transcriptomics revealed significant alterations in the composition and transcriptional programs of cTECs, mTECs, and thymic mimetic cells, linking Zfp36l1 and Zfp36l2 deficiency to a widespread increase in metabolic gene dysregulation in adult dcKO TECs. The erosion of the TEC compartment and the accumulation of age-associated TECs suggested impaired differentiation of mature lineages from their progenitors. Concordantly, fate-mapping analysis revealed that dual deficiency in Zfp36l1 and Zfp36l2 disrupted the canonical developmental trajectory from β5t-expressing TEC progenitors into mature TECs. Our findings uncover a previously unappreciated layer of post-transcriptional regulation in TEC biology, identifying a cooperative role for ZFP36L1 and ZFP36L2 in orchestrating TEC differentiation to sustain thymic function and prevent premature involution.

Glycosaminoglycans (GAGs) are a structurally and chemically diverse family of sulfated polysaccharides that constitute a major component of the neural extracellular matrix and cell surface proteoglycans, where they exert pivotal regulatory functions in axon growth, guidance, synaptic organization, and regeneration. By forming highly specific and context-dependent interactions with axonal receptors, GAGs orchestrate the spatial patterning and temporal dynamics of signaling events after injury. Accumulating evidence indicates that the biological activities of GAGs are not dictated merely by their presence but are finely tuned by their sulfation codes, chain length, and domain organization. Recent mechanistic studies have revealed that distinct GAG species, particularly chondroitin sulfate (CS) and heparan sulfate (HS), exert opposing effects on axonal behavior through shared receptor systems. In the injured central nervous system (CNS), CS-rich extracellular matrices, prominently associated with reactive astrocytes and perineuronal nets, act as potent inhibitors of axon regeneration. These inhibitory effects are mediated through selective engagement of receptors such as protein tyrosine phosphatase sigma (PTPσ) leading to suppression of cytoskeletal dynamics and growth cone motility. In contrast, specific HS motifs promote axon elongation by inhibiting PTPσ. Based on these insights, therapeutic strategies targeting GAG biology have gained considerable attention. Approaches such as enzymatic digestion of inhibitory CS chains, development of synthetic or biomimetic GAGs, modulation of sulfation patterns, and gene editing of GAG-modifying enzymes have demonstrated encouraging efficacy in preclinical models of spinal cord injury, traumatic brain injury, and neurodegenerative disorders. Together, these findings indicate GAGs not only as passive structural components but as active, druggable regulators of axon growth and regeneration. This review integrates current advances in GAG structural biology, receptor interactions, and enzymatic regulation to provide a comprehensive framework for understanding how GAGs govern axonal behavior. We highlight unresolved questions and emerging opportunities for exploiting GAG-mediated mechanisms as actionable targets for next-generation neurorestorative therapies.

Rice grain yield is largely determined by grain number per panicle, however,the molecular basis for this key trait remains elusive, particularly regarding how energy metabolism coordinates with panicle development. To elucidate this, we performed EMS mutagenesis of the OsOTUB1 loss-of-function mutant npt1, and isolated npt-s1, a suppressor reverting the high grain number phenotype of npt1. Map-based cloning identified that NPT-S1 encodes OsSnRK1β1A, a regulatory subunit of the SnRK1 energy-sensing complex. Functional analyses showed that OsSnRK1β1A promotes grain number by suppressing energy catabolism. Mechanistically, OsSnRK1β1A binds OsSnRK1α1 and, through N-terminal myristoylation, restricts its nuclear localization, thereby linking energy status to developmental outputs. Furthermore, we uncover that OsOTUB1 directly interacts with OsSnRK1β1A, exerting both competitive inhibition and K63-linked deubiquitination, with the latter triggering 26S proteasome-mediated degradation. Genetic and transcriptomic analyses indicate that this module determines grain number by reshaping global carbon, nitrogen, and lipid metabolism to prioritize reproductive allocation. Crucially, we demonstrate that engineered upregulation of OsSnRK1β1A via CRISPR/Cas9-mediated promoter editing of CAREOSREP1 and CCAAT-box consistently increases grain yield without compromising plant architecture. Together, our findings reveal a layered signaling pathway refined by post-translational modification, in which the OsOTUB1-OsSnRK1β1A module couples energy status to panicle development, providing both a mechanistic framework and actionable targets for breeding high-yield rice.

To test whether unilateral recurrent laryngeal nerve (RLN) transection elicits side specific transcriptomic responses in rat vocal fold compartments. We compared the medial thyroarytenoid (MTA) muscle and mucosa on the left versus right, accounting for baseline laterality. Unilateral RLN transection was performed in five adult rats (Left RLN: 2-males, 1-female; Right RLN: 1-male, 1-female). 5-weeks post-injury, the medial thyroarytenoid (MTA) muscle and vocal fold mucosa were harvested for RNA sequencing. Differential expression analysis compared Left-denervated versus Right-denervated tissues. A separate control Left-versus-Right analysis (1-male; 1-female) was used to assess baseline laterality and to contextualize TF transcription-factor inferences. TF activity was inferred using perturbation-based signatures, and baseline trends were used to classify overlapping signals as consistent with, opposite to, or distinct from baseline laterality. Left RLN denervation elicited distinct transcriptional responses in both compartments. In mucosa, TFs governing epithelial stability were reduced while regenerative cues were activated, suggesting impaired differentiation and recruitment of progenitor-like programs. In MTA, left-sided injury increased TFs consistent with stress signaling and mitochondrial compensation. TFs involved in epigenetic stability were reduced. Lateralized activity was observed in developmental regulators putatively related to positional memory or differential stress adaptation. Pathway analysis revealed enrichment of skeletal development processes in MTA and immune/matrix regulation in mucosa, indicating coordinated remodeling across muscle and epithelial compartments. RLN injury produces side-specific muscle and mucosal changes, with left-sided denervation showing stronger atrophy and stress responses. These results emphasize the importance of laterality and coordinated tissue adaptation. NA.

Olfactory sensory neurons comprise a population of highly heterogeneous subtypes. One important mechanism contributing to neuronal diversity is post-transcriptional regulation, in which isoform heterogeneity is an important component. Comprehensive profiling of transcript isoforms in olfactory sensory neurons is therefore essential for understanding the molecular mechanisms underlying their diversity. By integrating single-cell long-read sequencing with conventional 3' RNA sequencing, we demonstrated that these neurons contain extensive isoform diversity. We identified widespread UTR remodeling and isoform switching associated with developmental stage and spatial projection pattern, providing compelling evidence for the crucial regulatory mechanism underlying OSN diversity. Furthermore, we observed co-expression of multiple isoforms from the same olfactory receptor gene within individual olfactory sensory neurons, including some predicted to encode complete transmembrane domains. Together, these data provide a resource and framework for studying how specific isoforms contribute to olfactory sensory neuron identity, axon targeting, and the maintenance of singular olfactory receptor expression.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by widespread structural brain alterations, yet the specific patterns of brain atrophy and their underlying genetic mechanisms remain incompletely understood. Here, we integrated large-scale neuroimaging meta-analysis with population-scale imaging genetics to systematically characterize the genetic architecture linking gray matter volume (GMV) abnormalities to PD. We first performed a meta-analysis of structural MRI studies comprising 3,212 patients with PD and 2,056 controls, identifying robust patterns of GMV reduction and assessing differences across medication states. Using these meta-analytically defined regions as imaging phenotypes, we extracted GMV measures from the UK Biobank and conducted genome-wide association analysis (GWAS). This analysis identified 12 significant SNPs associated with PD-related GMV atrophy. Furthermore, we performed pleiotropy analysis and identified 22 SNPs jointly associated with PD risk and GMV reduction. Functional enrichment analyses revealed that these shared genes converge on pathways involved in clathrin-mediated endocytosis and synaptic vesicle recycling. Spatiotemporal transcriptomic profiling further characterized the developmental expression patterns of these genes, while molecular docking analyses suggested potential therapeutic targets. Together, these findings provide a comprehensive characterization of the genetic architecture linking brain structural abnormalities to PD, offering new molecular insights into the mechanisms underlying neurodegenerative brain damage and potential avenues for therapeutic intervention.

IVM Rescue is based on the in vitro maturation of mainly Germinal Vesicle (GV) oocytes collected from stimulated cycles. The objective was to investigate the effects of growth hormone (GH) and autologous cumulus cells co culture (CC) on oocyte meiosis resumption and maturation after 32h post cumulus denudation, in order to obtain additional embryos for the couple as a rescue system to increase the changes of cumulative pregnancy. Our study concerned 300 patients who underwent ICSI cycles, during which a total of 1940 cumulus-complex-oocytes were retrieved, giving 1260 metaphase II stage (MII), 200 at the metaphase I stage, and 480 at the Germinal Vesicle (GV) stage. Mature oocytes were microinjected on the same day of retrieval. Immature GV oocytes were divided into four groups, with the first undergoing in vitro maturation (IVM) without cumulus cells (group 1) and the second undergoing IVM with CC (group 2), the third undergoing IVM without CC and with GH (group 3), the fourth undergoing IVM with CC and with GH (group 4). After 32 hours of IVM, the matured oocytes, underwent microinjection, followed by embryonic development monitoring. When comparing the IVM outcomes, we observed a significant increase in oocyte maturation, fertilization rates and the percentage of 8-cell embryos on day 3 across the different study groups (p < 0.001) (Figures 2, 3, 4, and 5). Furthermore, all study groups (1-4) exhibited notably blastulation rates, with group 3 demonstrating the most promising clinical outcomes. A preliminary pregnancy rate of approximately 20% was recorded in group 3, suggesting a potential improvement in the developmental competence of oocytes matured under specific conditions. The IVM rescue of germinal vesicle oocyte could serve as an additional strategy to increase the chance getting extra embryos to patients. Autologous cumulus cells co culture combined to GH supplementation to IVM media, appear to play a crucial role to enhance successful meiosis resumption, oocyte maturation and competency to support embryos development when the injected the spermatozoa is not carrier of severe genome and epi genome decays.