Bernadette Simone de Bakker

Studies in anatomy are frequently performed through dissection and histology as investigative methods. These techniques are, however, destructive and struggle to capture the peripheral nerves over larger areas, such as the pelvis, and their trajectories thus remain elusive. This study aimed to explore the capabilities of non‐destructive micro‐CT in identifying small nerves in the periphery of the pelvic area and map them in human fetal development. Six human fetal pelvic samples were derived from the Dutch Fetal Biobank; samples were contrast enhanced with B‐Lugol and scanned through micro‐CT imaging. Scans were segmented using Avizo Amira software to quantify nerves entering the rectum by crossing the longitudinal muscle layer and visualize their trajectory in relationship to pelvic organs across development age range and sex. Results were verified with haematoxylin and eosin stained histological slices. The following conclusions were found: (1) Micro‐CT is able to resolve nerves with a diameter larger than 60 μm in the periphery of the pelvic area in full fetal pelvises of 4 cm in size. (2) Both above and below the level of the levator ani, small lateral nerves enter the anal canal by penetrating the longitudinal muscle layer. (3) Males appear to have more crossing nerves than females. (4) A developmental shift was observed with more nerve crossings below the levator ani muscle in older fetuses. Micro‐CT was successfully applied to scan human fetal pelvic samples to study nerves and provides a new way to analyse topographical nerve development. Microscale nerves cross to the anal canal at all levels, which should be taken into account when operating in this area.

Introduction: The ecto-endodermal boundary in the human oral cavity remains debated. Rather than a distinct line, this transition forms a complex interface, especially in the developing mouth and pharynx. This ambiguity is clinically relevant, as, for example, HPV-induced tumors often arise where ecto- and endoderm meet. The boundary is generally placed at the posterior third of the tongue and behind the uvula, though its developmental basis remains unclear. This review summarizes the literature on the embryological development of the mouth and pharynx to trace origins and interactions of ectodermal and endodermal derivatives and identify potential tumor initiation regions. Methods: PubMed articles on oral structures were reviewed to approximate the ecto-endodermal border. Results: Teeth originate from ectoderm. The origin of salivary glands and papillae depends on their location. No study reports were found for the tonsils, incisive papilla, tubarial glands, and faucial pillars. Conclusions: A clear educational image of the origin of the structures of the human mouth is made to help identify regions of risk for oral cancer.

Kees de Jong was a distinguished anatomist and embryologist whose influence reached across generations of students and colleagues, as well as the international plastination community. After obtaining his MD from the University of Amsterdam, he devoted his career to anatomy and embryology, disciplines in which he remained active for more than four decades. He spent most of his professional life at Amsterdam UMC, in the Department of Medical Biology, section of Clinical Anatomy and Embryology, where he became a cornerstone of anatomical education. He was widely recognized as an exceptional teacher of gross anatomy, guiding students through the complexities of the human body with clarity, precision, and a strong sense of structure. His explanations, often introduced with the disarming phrase “Oh, but that is very simple,” revealed not only anatomical detail but also the underlying logic and coherence of the human body. He combined rigor with accessibility, maintaining high standards while remaining deeply committed to his students' development.

Cerebrovascular disorders, encompassing conditions such as stroke, aneurysms, and arteriovenous malformations, are often associated with developmental malformations of the intracranial arterial system, including the circle of Willis. The circle of Willis plays a crucial role in establishing a collateral vascular network essential for ensuring adequate cerebral blood supply. However, the intricate process of human intracranial vascular development, known as vascular neuroembryology, remains complex and incompletely understood. The diverse array of anatomical vascular variations observed in clinical practice is a direct outcome of this developmental process. We present a chronological overview of human neurovascular embryology using stage-resolved three-dimensional reconstructions of the developing intracranial arterial system. Histological sections of 26 human embryos ranging from Carnegie stages (CS) 11 to 23 were digitally reconstructed and manually segmented in Amira software (versions 5.3–5.6; Thermo Fisher Scientific, Waltham, MA, USA) to generate detailed 3D models of the cranial vasculature and adjacent anatomical structures, including the neural tube, cranial nerves, eye, and ear. Sequential 3D reconstruction revealed progressive remodeling of the primitive cranial vasculature and key developmental transitions underlying formation of the circle of Willis. By integrating these developmental observations with existing embryological literature, we refine current models of neurovascular development, with particular emphasis on the ophthalmic and trigeminal arterial systems. These findings provide an updated developmental framework for interpreting normal and variant intracranial vascular anatomy encountered in clinical practice.

The clitoris is one of the least studied organs of the human body. The detailed anatomy of the clitoris is challenging to address through a gross dissection, as most of its parts are embedded internally, surrounded by pubic bone and several pelvic organs. While clinical imaging methods such as magnetic resonance imaging can capture the gross 3D morphology, they lack the spatial resolution required to resolve the detailed structures. In this study, we generated micron-scale computed tomography images of the female pelvises, leveraging a synchrotron radiation X-ray source. This unique data revealed the complex trajectory of the dorsal nerve of the clitoris, the main sensory nerve of the clitoris. Notably, the nerve trunks within the clitoral glans were revealed, with the maximum diameter ranging from 0.2 to 0.7 mm. They showed a tree-like branching pattern projecting towards the surface of the glans. We also revealed that some branches of the dorsal nerve of the clitoris ramify to innervate the clitoral hood and mons pubis. Finally, the posterior labial nerve, a branch of the perineal nerves, was shown to innervate the surroundings of the clitoris and the labial structures. These findings have an immediate impact on operations performed around the vulva area, such as gender-affirmation surgery and reconstruction surgery after genital mutilation.

We present the Human Organ Atlas (HOA), an open data repository making accessible multiscale three-dimensional imaging of human organs. The repository also provides software tools and training resources enabling worldwide access, sharing, and analysis of these datasets, facilitating further research and the continued expansion of the HOA. The images are generated using a synchrotron imaging technique, hierarchical phase-contrast tomography (HiP-CT), that uses the ESRF’s Extremely Brilliant Source, spanning whole-organ imaging at ~20 micrometers/voxel with local volumes of interest within intact organs imaged down to ~1 micrometer/voxel. This offers a comprehensive exploration of human anatomy, providing unparalleled insights into intricate structures and spatial relationships. The HOA offers researchers, clinicians, and educators a valuable resource for anatomical study, image analysis, medical education, and large-scale data mining.

Introduction: The human face develops through a complex sequence of growth and fusion events involving multiple pharyngeal arch derivatives. Disruptions in these processes can result in congenital anomalies such as cleft lip and/or palate (CL/P), which occur in approximately 1.6 per 1000 live births in Europe. Patients with CL/P often experience difficulties regarding feeding and speech, and studies suggest an increased risk of psychosocial difficulties. Understanding the morphological development and timing of secondary palate formation is essential for clarifying the pathogenesis of CL/P and identifying critical developmental periods during pregnancy. In this study, we aimed to evaluate the timing and morphological changes of the secondary palate in human embryos between Carnegie Stages 17–23 and fetuses aged 9–11 weeks post‐conception (PC). Methods: Histological sections and micro‐CT scans of 26 human specimens, evenly distributed across these developmental stages, were analyzed. Results: The results showed that palatal shelves first appear at CS18 and continue vertical outgrowth until CS22. At CS22, the shelves start to reorient horizontally and further extend medially. Shelf contact is observed at CS23, marking the onset of fusion, which is completed during or after 9 weeks PC. Conclusions: These findings refine the timeline of human secondary palate development. Importantly, identifying this critical developmental window suggests that current guidelines for administering medications during early pregnancy should be reevaluated, as drug exposure during this sensitive period may increase the risk of palatal malformations.

The adult mammalian heart has a limited regenerative capacity. Following injury, cardiomyocytes undergo a hypertrophic response accompanied by polyploidization, which has been described as a barrier to proliferation and regeneration of the heart ^1,2 . However, the unique molecular programs of polyploidy, or genome multiplied cardiomyocytes, and their influence on the disease-related myocardial remodelling process remains unclear. Here, we integrate single-nuclei and high-resolution spatial multi-omics across human, rat, and mouse hearts to define novel cardiac cell states and their tissue niches in ischemic and non-ischemic heart disease. Computational analysis across scales allowed us to generate detailed networks of the cardiac tissue remodelling process as well as tissue and sub-cellular environments uniquely enriched in polyploid cardiomyocytes or their diploid origins. We identify a conserved, dichotomous transcriptional program distinguishing diploid from polyploid cardiomyocytes. Polyploid cardiomyocytes demonstrated rewired metabolic and chromatin-remodeling transcriptional programs and recapitulate the gene signature of immature human fetal cardiomyocytes. Notably, we observe that polyploid cardiomyocytes—rather than the general myocyte population—are the primary sites of enrichment for major heart-failure drug targets, including the mineralocorticoid, β1-adrenergic, and glucagon-like peptide-1 receptors. Based on our cross-species dataset we further identified TNIK, a Wnt-pathway regulator expressed in polyploid cardiomyocytes across species, as a potential therapeutic target and demonstrate that pharmacological TNIK inhibition improves cardiac function after myocardial infarction in rats. Together, this species-spanning, disease-resolved study redefines cardiomyocyte heterogeneity in heart disease and suggests a therapeutic path to heart failure treatment by targeting polyploid cardiomyocytes.

Objective: To establish normative data for key morphometric measurements in prenatal mandibular development. Methods: Forty-two human embryonic and fetal specimens, ranging from 8 to 37 weeks of gestational age (GA), without known abnormalities, were selected. Mandibles were segmented on histologic, micro-CT, or MDCT images. Fourteen anatomic landmarks were annotated, and key morphometric measurements were extracted, including bigonial width, bicondylar width, body length, ramus height, and gonial angle. Quadratic regression models were fitted to the measurements as a function of gestational age to assess developmental trends. Results: Mandibular ossification was first observed at Carnegie stage 19 (8+4 wk GA), adjacent to Meckel cartilage. Strong, statistically significant correlations with GA were found for all linear measurements ( R ² >0.95, P R ² =0.65, P <0.0001). Conclusion: This study provides comprehensive normative reference data for prenatal mandibular development, spanning early embryonic to late fetal stages. The established growth curves can serve as valuable tools in prenatal diagnostics, enabling earlier and more accurate detection of craniofacial anomalies associated with syndromic and nonsyndromic mandibular malformations. The presented normative data may also aid age estimation in forensic and archeological investigations.

Each year, around 23 million miscarriages occur worldwide, which have a substantial emotional impact on parents, and impose significant societal costs. While medical care accounts for most expenses, work productivity loss contributes significantly. Addressing underlying causes of miscarriage could improve parents’ mental health and potentially their economic impact. In most countries, investigations into miscarriage causes are only recommended after recurrent cases, focusing mainly on maternal factors. Fetal and placental tissue are rarely examined, as current guidelines do not advise routine genetic analyses of pregnancy tissue, because the impact of further clinical decision making and individual prognosis is unclear. However, this leaves over 90% of all miscarriage cases unexplained and highlights the need for alternative methods. We therefore conducted a narrative review on genetic analysis, autopsy, and imaging of products of conception (POC). Karyotyping, QF-PCR, SNP array, and aCGH were reviewed in different research settings, with QF-PCR being the most cost-effective, while obtaining the highest technical success rate. Karyotyping, historically being considered the gold standard for POC examination, was the least promising. Post-mortem imaging techniques including post-mortem ultrasound (PMUS), ultra-high-field magnetic resonance imaging (UHF-MRI), and microfocus computed tomography (micro-CT) show promising diagnostic capabilities in miscarriages, with micro-CT achieving the highest cost-effective performance. In conclusion, current guidelines do not recommend diagnostic testing for most cases, leaving the majority unexplained. Although genetic and imaging techniques show promising diagnostic potential, they should not yet be implemented in routine clinical care and require thorough evaluation within research settings—assessing not only diagnostic and psychosocial outcomes but also economic implications.