Our understanding of human fetal cerebellum development during the late second trimester, a critical period for the generation of astrocytes, oligodendrocytes, and unipolar brush cells (UBCs), remains limited. Here, we performed single-cell RNA sequencing (scRNA-seq) in human fetal cerebellum samples from gestational weeks (GWs) 18-25. We find that proliferating UBC progenitors distribute in the subventricular zone of the rhombic lip (RLSVZ) near white matter (WM), forming a layer structure. We also delineate two trajectories from astrogenic radial glia (ARGs) to Bergmann glial progenitors (BGPs) and recognize oligodendrogenic radial glia (ORGs) as one source of primitive oligodendrocyte progenitor cells (PriOPCs). Additionally, our scRNA-seq analysis of the trisomy 21 fetal cerebellum at this stage reveals abnormal upregulated genes in pathways such as the cell adhesion pathway and focal adhesion pathway, which potentially promote neuronal differentiation. Overall, our research provides valuable insights into normal and abnormal development of the human fetal cerebellum.

This study aimed to observe human trapezius muscle (TpzM) development during early fetal period and apply diffusion tensor imaging (DTI) analysis to describe the muscle architecture that leads to physiological functions. Human embryonic and early fetal specimens were selected for this study. TpzM was first detected at Carnegie stage 20. The position of the TpzM changed with the formation of the scapula, clavicle, and vertebrae, which are its insertions and origins. DTI revealed the fiber orientation from each vertebral level to dissect each muscle. Fiber orientation in the ventral view gradually changed from the cervical to thoracic vertebrae, except for the middle part at which the insertions changed, which was almost similar in all early fetal specimens. The TpzM volume increased from C1 to C7 in the upper part, reached local maxima at C6 and C7 in the middle, and then decreased. These muscles can be categorized into three parts according to their insertions and presented with the features of each part. The fiber orientation and distribution of the three parts at the vertebral level were almost constant during the early fetal period. The border between the upper and middle parts was mainly located around the C6 and C7 vertebral levels, whereas the middle and lower parts were between the Th1 and Th2 vertebral levels. A three-dimensional change in the fiber orientation in the upper part of the TpzM according to the vertebral level was noticeable. Our data will help to elucidate the developmental processes of TpzM.

At the angle of the mouth, spoke-like muscle bundles converge at the \"modiolus,\" which is believed to appear in utero. The aim of this study was to investigate the growth of the modiolus histologically. We studied frontal histological sections of the face from 12 midterm and six near-term fetuses. At midterm, a convergence of the levator anguli oris (LAOM) and depressor anguli oris (DAOM) was frequently present, and another convergence of the LAOM with the platysma (PM) or orbicularis oris (OOM) was also often evident. At near-term, muscle fiber merging or interdigitation was classified into nine combinations, five of which were frequently seen: LAOM-PM, LAOM-DAOM, zygomaticus major (ZMM)-orbicularis oris (OOM), buccinator (BM)-LAOM, and BM-PM. These combinations existed at slightly different depths and/or sites, thus allowing the angle of the mouth to receive multiple muscles. Notably, tissues interposed between the muscle fibers were limited to a thin epimysium at each crossing or interdigitation. Therefore, the LAOM, DAOM, OOM, BM, and PM appear to form a basic configuration at birth, but the development and growth were much delayed than the classical description. The modiolus is not a specific fibromuscular structure but simply represents a cluster of muscle convergence sites. Even at meeting between an elevator and depressor, a specific fibrous structure seems unlikely to connect the epimysium for the muscle convergence. Instead, the central nervous system appears to regulate the activity of related muscles to minimize tension or friction stress at the meeting site.

Previous studies have poorly described the initial development process of the tendinous intersections of the rectus abdominis muscle (RAM). The present study aimed to observe the formation of tendinous intersections in the RAM during the early fetal period using diffusion tensor imaging (DTI). Fifteen human fetal specimens (crown-rump length [CRL]: 39.5-93.7 mm) were selected. Three-dimensional measurements revealed that Zone-4 (i.e., the zone between the pubic symphysis and the caudal base of the umbilical ring in the RAM) had a smaller width and was thicker than Zone-1 and Zone-2 (i.e., the zones between the costal arch and the cranial base of the umbilical ring) and Zone-3 (i.e., the zone at the umbilical ring). Characteristics of tendinous intersections in the RAM during the early fetal period were assessed according to number, size, type, laterality, and sex. The mean number of tendinous intersections on both sides was 3.1 (range: 2.0-4.0), and 21% of specimens had only two tendinous intersections, which was higher than that reported in previous adult studies. The present data suggest that the formation of tendinous intersections was still in progress in specimens with two tendinous intersections in the RAM and that the third tendinous intersection was formed in Zone-2. Ordinal logistic regression via generalized estimating equations revealed that the odds for a higher type of tendinous intersections in Zone-1 and Zone-2 were significantly higher than those in Zone-4 (adjusted odds ratio: 14.85, 8.84). The odds for the presence of incomplete types (tendinous intersections that could not completely transverse the RAM) in Zone-3 were significantly higher than those in Zone-1 (adjusted odds ratio: 7.4). The odds for missing tendinous intersections in Zone-4 were significantly higher than those in Zone-1 (adjusted odds ratio: 20.5). These zonal differences in the formation of tendinous intersections were consistent with those observed in previous adult studies. In this study, DTI detected tendinous intersections in a sample with a CRL of 45.8 mm (approximately 11 weeks of gestation), which is earlier than that in previous histological findings, indicating that the RAM does not have mature tendinous intersections until the 17th week of gestation. In conclusion, DTI could detect the premature differentiation of tendinous intersection formation. Our data may aid in elucidating the developmental processes of tendinous intersections in the RAM.

OBJECTIVE: The aim of this study was to demonstrate the establishment of adrenal sparing in intrauterine growth restricted (IUGR) human fetuses. IUGR fetuses are a subgroup of small for gestational age (SGA) fetuses that are unable to reach their own growth potential because of chronic hypoxia and undernutrition. We hypothesized that in IUGR fetuses the adrenal gland is relatively larger and secretion of noradrenaline (NA), adrenaline (A), and cortisol is increased.
METHODS: This is a prospective observational study including 65 singleton pregnancies (42 IUGR and 23 controls). Using two-dimensional ultrasound, we measured fetal adrenal diameters and adrenal/abdominal circumference (AD/AC) ratio between 25 and 37 weeks. We considered only one measurement per fetus. In 21 pregnancies we also measured NA, A, and cortisol levels in arterial and venous fetal cord blood collected at the time of delivery.
RESULTS: The AD/AC ratio was significantly higher in IUGR fetuses than in controls. Cord NA and A levels were significantly higher in IUGR fetuses than in controls. An increase in cortisol secretion in IUGR fetuses was observed but the difference was not statistically significant.
CONCLUSIONS: Adrenal sparing correlates with a relative increase in adrenal measurements and function.

Introduction Age-specific reference intervals for the extensor digiti minimi muscle (EDMM) in the human fetus may be relevant in the detailed evaluation of the musculoskeletal systems with potential relevant aspects for surgical treatment. The aim of the study was to examine the age-specific reference intervals and growth dynamics of the EDMM in relation to its length, width, projection surface area and volume. Material and methods The examined material included 70 human formalin-fixed fetuses of both sexes (37♀, 33♂) aged from 17 to 29 weeks. With the use of anatomical dissection every EDMM was visualized, recorded in a form of JPG formats and analyzed by the digital image analysis system and statistical methods. Results No variability of the EDMM was found. All the morphometric parameters of the EDMM revealed neither sex nor laterality differences. With fetal age most linear parameters of the EDMM concerning its examined lengths and widths increased in accordance with natural logarithmic functions. The only two exceptions to this referred to the belly width of EDMM measured at its mid-length and the tendon width of EDMM measured proximal to the extensor retinaculum of wrist, which both followed square root functions. The projection surface areas of the EDMM followed natural logarithmic functions, while the volumetric growth of the EDMM was proportionate to fetal age. Conclusions The variability of the EDMM in the human fetus is minimal. The morphometric data of the EDMM represents age-specific reference intervals of clinical significance. Morphometric parameters of the EDMM reveal neither sex nor laterality differences. The EDMM displays three different growth dynamics: from gradual growth deceleration according to both natural logarithmic functions (total length of the muscle and its tendons, belly length, tendon lengths, belly width at its origin, tendon width at its insertion, and projection surface areas) and square root functions (belly width at its mid-length and tendon width in the pre-retinacular segment) to a proportionate growth (total volume).

BACKGROUND: In adults, the intermediate tendon of digastricus muscle usually runs along the medial or lateral side of the stylohyoideus muscle insertion. To provide a better understanding of the variations, we examined the topographical anatomy of the muscle and tendon in fetuses.
METHODS: We examined histological sections from six early-term, 26 mid-term and six near-term fetuses (approximately 8-9, 12-18 weeks and 25-33 weeks).
RESULTS: At early-term, an initial sheath of intermediate tendon of digastricus muscle received the stylohyoideus muscle at the superior aspect. The muscle and tendon was distant from the hyoid. At mid-term, near the insertion to the hyoid greater horn, the stylohyoideus muscle consistently surrounded more than 2/3 of the intermediate tendon circumference. In contrast, we found no near-term specimen in which the stylohyoideus muscle surrounded the intermediate tendon. The multilayered tendon sheath was fully developed until near-term and connected to the body of hyoid by an intermuscular septum between the thyrohyoideus muscle and one or two of suprahyoid muscles. Therefore, the hyoid insertion of the styloglossus muscle was a transient morphology at mid-term.
CONCLUSIONS: The stylohyoideus muscle insertion was appeared to move from the tendon sheath to the hyoid greater horn and, until near-term, return to the tendon sheath. A fascia connecting the tendon sheath to the body of hyoid was strengthened by the suprahyoid and infrahyoid muscles. The latter muscles seemed to regulate fixation/relaxation of the intermediate tendon to the hyoid. The stylohyoideus muscle slips sandwiching the intermediate tendon might be a rare morphology.

The popliteal fossa presents an extensive diamond-shaped topographical element on the posterior aspect of the knee. With the use of classical anatomical dissection, digital image analysis of NIS Elements AR 3.0 and statistics we morphometrically analyzed the size of the popliteal fossa in human fetuses aged 17-29 weeks of gestation. Morphometric parameters of the popliteal fossa increased logarithmically with fetal age: y = -44.421 + 24.301 × ln (Age) for length of superomedial boundary, y = -41.379 + 22.777 × ln (Age) for length of superolateral boundary, y = -39.019 + 20.981 × ln (Age) for inferomedial boundary, y = -37.547 + 20.319 × ln (Age), for length of inferolateral boundary, y = -28.915 + 15.822 × ln (Age) for transverse diameter, y = -69.790 + 38.73 × ln (Age) for vertical diameter and y = -485.631 + 240.844 × ln (Age) for projection surface area. Out of the four angles of the popliteal fossa the medial one was greatest, the inferior one the smallest, while the lateral one was somewhat smaller than the medial one and approximately three times greater than the superior one, with no difference with fetal age. In terms of morphometric parameters the popliteal fossa in the human fetus displays neither male-female nor right-left differences. In the popliteal fossa, growth patterns of its four boundaries, vertical and transverse diameters, and projection surface area all follow natural logarithmic functions. All the morphometric data is considered age-specific reference intervals, which may be conducive in the diagnostics of congenital abnormalities in the human fetus.

In human fetuses, the left hepatic artery (LHA) issues the marginal artery that runs along the umbilical vein and, sometimes, reaches the umbilicus. The further observation demonstrated that, in 5 of 12 Japanese midterm fetuses (crown-rump length mm: 46, 50, 54, 59, 102), the marginal artery issued not only a thin umbilical branch but also a liver parenchymal branch that took a posterosuperior recurrent course in a peritoneal fold and supplied the anterior surface of the liver left lobe (segment III). However, in 22 Spanish fetuses of which gestational ages corresponded to the Japanese ones, we did not find the parenchymal branch. Therefore, between human populations, there seemed to be a considerable difference in the incidence as to whether or not the marginal artery issues the liver parenchymal branch. The parenchymal branch might be degenerated at the later stages due to friction between the liver free surface and growing diaphragm.

UNASSIGNED: The temporomandibular joint (TMJ) is a synovial joint that allows the complex movements essential for life. It connects the jawbone to the skull, working as a sliding hinge. Moreover, pluripotent stem cells are a source of precursors and tissue-specific cells in developing organisms, however, their biodistribution in developing fetal tissues is weakly studied. The aim of our study was analyse immunohistochemical expression of Nanog, Oct-4, Sox-2 and Stat-3 and Sox-5, in TMJ tissue samples from human fetuses aged between the 12th and 20th weeks of intrauterine life.
UNASSIGNED: We fixed and processed TMJ tissue samples from human fetuses, histological sections and immunohistochemical procedures were carried out.
UNASSIGNED: TMJ histological studies examination did not reveal any difference in the tissue organization between the samples in the studied periods. Immunohistochemical analysis demonstrated that Oct-4 and Sox-2 lack their expression in TMJ. In contrast, Nanog was expressed in nucleous of proliferative layer of mandibular condyle, Stat-3 was expressed in nuclear cells of articular disc, Stat-3 and Sox-5 showed positive nuclear and cytoplasmic immunostaining in codrocyte layers and in ossification areas.
UNASSIGNED: Nanog acts in maintanence of pluripotency, Stat-3 in articular disc acts as a transcriptional factor. Stat-3 and Sox-2 act in chondrocyte and osteoblast diferentiation. Distribution of the cells, which express Nanog, Stat-3, and Sox-5 in TMJ tissue during fetal development, can help further understand its physiology, pathology, and repairing capacities.