Journal of Developmental Biology最新文献

Placenta Accreta Spectrum (PAS) disorders, including placenta accreta, increta, and percreta, are serious obstetric conditions characterized by abnormal placental adherence to the uterine wall. With increasing incidence, PAS poses significant risks, primarily through massive hemorrhage during or after delivery, often necessitating hysterectomy. Key risk factors include prior cesarean sections, uterine surgery, and placenta previa diagnosis. In this review, we will examine the pathophysiology of PAS, with a focus on the mechanisms underlying abnormal trophoblast invasion and defective decidualization. We will highlight the role of uterine scarring, extracellular matrix remodeling, dysregulated signaling pathways, and immune and vascular alterations in disrupting the maternal-fetal interface, ultimately predisposing to morbid placentation and delivery complications. We will also discuss the life-threatening complications of PAS, such as shock and multi-organ failure, which require urgent multidisciplinary intensive care, as well as the optimization of management through preoperative planning and intraoperative blood loss control to reduce maternal morbidity and mortality.

Background. Gestational diabetes mellitus (GDM) induces maternal hyperglycemia, which may alter fetal cardiac structure and function, increasing short- and long-term cardiovascular risks. Purpose. To systematically review the evidence on the fetal cardiac structural and functional effects of GDM, to explore the diagnostic role of novel imaging and biochemical biomarkers, and to summarize the long-term cardiovascular complications associated with GDM. Materials and Methods. A systematic search of PubMed, Scopus, and Cochrane Library was conducted according to the PRISMA guidelines. All studies comparing cardiac outcomes in GDM and non-GDM pregnancies were included. Data on myocardial hypertrophy, diastolic and systolic function, imaging modalities, and biomarkers were extracted and qualitatively synthesized. Results. A total of twelve eligible studies were identified. Fetal cardiac hypertrophy and diastolic and early systolic dysfunction are common among GDM pregnancies and can be detected by dual-gate Doppler and speckle-tracking echocardiography. Abnormalities are observed in indices such as the myocardial performance index, E/A, E/e' ratios, and global longitudinal and circumferential strain in fetuses and may persist in the neonatal period. Alterations may be more pronounced for the right ventricle compared to the left. Septal hypertrophy is associated with elevated umbilical cord pro-brain natriuretic peptide. The risk of early-onset cardiovascular disease in the progeny of diabetic mothers is 29% higher, as evidenced by population-based cohort data. Conclusions. GDM is linked to fetal cardiac remodeling and an increased long-term cardiovascular risk. Early detection and customized interventions to reduce adverse outcomes may be achieved by integrating advanced echocardiographic techniques and biomarkers into prenatal surveillance.

Observations of the processes of oogenesis, fertilization, and the earliest embryonic development have given us the opportunity to estimate the importance of chromosomal distribution errors for the success of mammalian reproduction. It is now known that in the large volume of oocytes, zygotes and the first embryonic cells, the rearrangement of chromatin is associated with a complex rearrangement of cytoskeletal structures, which creates specific problems. This review discusses two main issues critical to the success of early embryos: Why oocyte meiosis is too frequently wrong in chromosomal segregation? Why the first zygotic mitoses are too frequently wrong in chromosomal segregation? We concluded the following: (1) The main cytoskeletal defects that disturb oocyte meiosis are a problematic connection between cytoskeleton and nucleoskeleton, unsuccessful movement of the spindle to the oocyte periphery, unstable anchoring of the spindle to oolemma, and deviations in meiotic spindle morphology; (2) The main cytoskeletal defects that disturb pronuclear unification are nonfunctional male centriole, unsuccessful forming of microtubule aster around the sperm centrosome, problematic movement of the two pronuclei towards each other and inappropriate contacts between centrosomes, microtubules and nuclear pore complexes; (3) Cytoskeletal defects that disturb zygote mitosis are unsuccessful forming of bipolar mitotic spindle, non-synchronized congression of maternal and paternal chromosomes, and unsuccessful attachment of kinetochores to microtubules.

Autophagy has a potential regulatory effect on spermatogenesis and testicular development. Dynamic alterations in the testicular autophagy of prepubertal mice were analyzed, and the relationship between autophagy levels and testicular development was clarified using C57BL/6 mice aged 1, 2, 4, 6, and 8 weeks. Transmission electron microscopy was used to identify autophagic vacuoles. The expression of autophagy-related proteins and PI3K/AKT/mTOR signaling pathway-related proteins was determined using Western blotting. Localization of microtubule-associated protein light chain 3 (LC3) and sequestosome 1 (p62) in testicular tissues was determined using immunofluorescence and immunohistochemistry. Autophagic vacuoles in spermatogenic cells increased gradually from weeks 1 to 4, peaked at 2 weeks, decreased sharply at 6 weeks, and were undetectable at 8 weeks. The expression of Beclin 1 autophagy-related protein, LC3-II, and p62 was highest at 2 weeks among the five age groups, whereas LC3-II and p62 were mainly localized in spermatogonia and spermatocytes. Moreover, low mTOR expression and its increased expression were detected at 1-2 weeks and 2-8 weeks, respectively. These results show that testicular autophagic levels exhibit a dynamic pattern of "increase (1-2 weeks) followed by a decrease (2-8 weeks)," providing a reference in determining the relationship between autophagy levels and testicular development.

Somatic cell nuclear transfer (SCNT) or cloning technology is widely used in agriculture and biomedicine. However, the application of this technology is limited by the low developmental competence of cloned embryos or fetuses, which frequently exhibit abnormal development of trophoblast cells or placentas. The purpose of this study was to investigate the possible causes of the erroneous placental development of SCNT-derived pig fetuses. The placental transcriptomic and lipidomic profiles were compared between 30-day-old SCNT- and artificial insemination (AI)-produced pig fetuses. Differentially expressed lipid metabolites between two groups of placentas were selected to test their effects on porcine trophoblast cell activity. The results showed that SCNT placentas exhibit impaired lipid metabolism and function. The level of a metabolite, lysophosphatidylcholine (LPC), in the glycerophospholipid metabolism pathway was substantially increased in SCNT placentas, compared with AI placentas. The elevation in LPC content may lead to impaired placental development in cloned pig fetuses, as LPC inhibited the proliferation and migration of porcine trophoblast cells. This study discovers a main cause of erroneous development of cloned pig fetuses, which will be beneficial for understanding the regulation of SCNT embryo development, as well as developing new methods to improve the efficiency of pig cloning.

Neurodevelopmental disorders (NDDs), including autism spectrum disorder, intellectual disability, and attention deficit hyperactivity disorder, are increasingly recognized as disorders of early brain construction arising from defects in neural stem and progenitor cell (NSPC) proliferation. NSPCs are responsible for generating the diverse neuronal and glial lineages that establish cortical architecture and neural circuitry; thus, their expansion must be tightly coordinated by intrinsic cell cycle regulators and extrinsic niche-derived cues. Disruption of these mechanisms-through genetic mutations, epigenetic dysregulation, or environmental insults-can perturb the balance between NSPC self-renewal and differentiation, resulting in aberrant brain size and connectivity. Recent advances using animal models and human pluripotent stem cell-derived brain organoids have identified key signaling pathways, including Notch, Wnt, SHH, and PI3K-mTOR, as central hubs integrating proliferative cues, while transcriptional and chromatin regulators such as PAX6, CHD8, SETD5, and ANKRD11 govern gene expression essential for proper NSPC cycling. Furthermore, prenatal exposure to teratogens such as Zika virus infection, valproic acid, or metabolic stress in phenylketonuria can recapitulate proliferation defects and microcephaly, underscoring the vulnerability of NSPCs to environmental perturbation. This review summarizes emerging insights into the molecular and cellular mechanisms by which defective NSPC proliferation contributes to NDD pathogenesis, highlighting convergence among genetic and environmental factors on cell cycle control. A deeper understanding of these pathways may uncover shared therapeutic targets to restore neurodevelopmental trajectories and mitigate disease burden.

Despite looking monotonous, liver histology represents a highly complex structure of hepatocytes, bile ducts and vessels. This complex interaction and development originate in embryology and remain in adult life. In this manuscript, we highlight the features of liver embryology, translating the events into pathologic features and opening possibilities for disease understanding and research. We revisit liver embryology, from biliary to vascular processes, stressing some developing abnormalities with a focus on the histological findings. With this manuscript, we hope to increase the awareness of the importance of embryology in diseases, prompting its detailed study.

We examined whether an increase in synaptic activity resulted in an increase in quantal size at the neuromuscular junction (NMJ) of third-instar Drosophila larvae. Spontaneous miniature excitatory postsynaptic currents (mEPSCs) or miniature excitatory postsynaptic potentials (mEPSPs) were recorded before and after nerve stimulation. We found that prolonged (60 s) or brief (1.25 s) nerve stimulation produced an increase in quantal size; this appears to be a general property of these synapses since it was seen at all four muscle fibers (MFs) used in this study. The effect was examined along Is and Ib terminals by expressing GCaMP in the MF membrane and examining postsynaptic Ca²⁺ signals produced by spontaneous transmitter release. The activity-dependent increase in quantal size occurred at both Is and Ib terminals, and the increase in frequency and amplitude of quantal events at individual synaptic boutons was correlated. Both the increase in quantal size and frequency were found to be dependent upon an increase in postsynaptic Ca²⁺, based on studies in which MFs were preinjected with the Ca²⁺ chelator BAPTA (1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). To examine the effect of postsynaptic activity on glutamate sensitivity, we iontophoresed glutamate pulses at the NMJ and recorded the glutamate-evoked excitatory postsynaptic potentials (gEPSPs). Trains of glutamate pulses produced an increase in gEPSP amplitude; this potentiation was not seen when Ca²⁺ was eliminated from the bath or after inhibiting calmodulin or CaMKII. The activity-dependent increase in quantal size may result from an increase in postsynaptic sensitivity due to activation of CaMKII.

Estrogen metabolites (EMs) play a local regulatory role in mammalian ovarian function. Among them, 2-hydroxyestradiol (2-OHE2) exerts dose-dependent effects on reproductive physiology, supporting either normal ovarian processes or contributing to pathological conditions. Specifically, 2-OHE2 modulates ovarian vasculature and progesterone biosynthesis, and at 1-10 nM concentrations, it enhances in vitro developmental competence and blastocyst quality in mouse oocytes. Conversely, doses below 1 nM show no appreciable effects, suggesting the existence of a biological activity threshold. However, the impact of supra-physiological concentrations remains largely unexplored. In this study, we investigated the effects of increasing 2-OHE2 doses (0.05, 0.50, and 5.00 µM) on oocyte meiotic progression and quality. Exposure to 0.50 and 5.00 µM significantly impaired oocyte maturation, while only the highest dose notably reduced the percentage of embryos developing to the blastocyst stage. Morphometric analysis during the GV-to-MII transition revealed altered first polar body morphology, defective asymmetric division, and disruptions in cytoskeletal organization, including enlarged meiotic spindles, increased F-actin cap angles, and aberrant microtubule-organizing centers distribution. These structural alterations were paralleled by distinct changes in cytoplasmic movement velocity patterns observed through time-lapse imaging during meiotic resumption. Together, these findings demonstrate that supra-physiological exposure to 2-OHE2 compromises oocyte maturation and developmental competence by perturbing key cytoskeletal dynamics and cellular architecture necessary for successful meiosis and early embryogenesis.

Wnt signaling is an ancient developmental mechanism that drives the initial specification and patterning of the primary axis in many metazoan embryos. Yet, it is unclear how exactly the various Wnt components interact in most Wnt-mediated developmental processes as well as in the molecular mechanism regulating adult tissue homeostasis. Recent work in invertebrate deuterostome sea urchin embryos indicates that three different Wnt signaling pathways (Wnt/β-catenin, Wnt/JNK, and Wnt/PKC) form an interconnected Wnt signaling network that specifies and patterns the primary anterior-posterior (AP) axis. Here, we detail our current knowledge of this critical regulatory process in sea urchin embryos. We also illustrate examples from a diverse group of metazoans, from cnidarians to vertebrates, that suggest aspects of the sea urchin AP Wnt signaling network are deeply conserved. We explore how the sea urchin is an excellent model to elucidate a detailed molecular understanding of AP axis specification and patterning that can be used for identifying unifying developmental principles across animals.