In the developing human musculoskeletal system, cell death with macrophage accumulation occurs in the thigh muscle and interdigital area. To comprehensively clarify the distribution of macrophages, we immunohistochemically examined 16 pairs of upper and lower extremities without the hip joint (left and right sides) obtained from 8 human fetuses at approximately 10-15 weeks of gestation. Rather than in muscles, CD68-positive macrophages were densely distributed in loose connective tissues of the flexor aspects of the extremities, especially in the wrist, hand and foot. In contrast, no or fewer macrophages were evident in the shoulder and the extensor aspects of the extremities. The macrophages were not concentrated at the enthesis of the tendon and ligament, but tended to be arranged along other connective tissue fibers. Deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling revealed apoptosis in the hand lumbricalis muscles, but not in the area of macrophage accumulation. Likewise, podoplanin-positive lymphatic vessels were not localized to areas of macrophage accumulation. Re-organization of the connective tissue along and around the flexor tendons of the hand and foot, such as development of the bursa or tendon sheath at 10-15 weeks, might require the phagocytotic function of macrophages, although details of the mechanism remain unknown.
Apoptosis ; Cell Death ; Connective Tissue ; Deoxyuracil Nucleotides ; Deoxyuridine ; Extremities ; Fetus ; Foot ; Hand ; Hip Joint ; Humans ; Ligaments ; Lower Extremity ; Lymphatic Vessels ; Macrophages ; Muscles ; Musculoskeletal System ; Pregnancy ; Shoulder ; Tendons ; Thigh ; Wrist

Carbonic anhydrase type IX (CA9) is known to express in the fetal joint cartilage to maintain pH against hypoxia. Using paraffin-embedded histology of 10 human fetuses at 10-16 weeks of gestation with an aid of immunohistochemistry of the intermediate filaments, matrix components (collagen types I and II, aggrecan, versican, fibronectin, tenascin, and hyaluronan) and CA9, we observed all joints and most of the entheses in the body. At any stages examined, CA9-poisitive cells were seen in the intervertebral disk and all joint cartilages including those of the facet joint of the vertebral column, but the accumulation area was reduced in the larger specimens. Glial fibrillary acidic protein (GFAP), one of the intermediate filaments, expressed in a part of the CA9-positive cartilages. Developing elastic cartilages were positive both of CA9 and GFAP. Notably, parts of the tendon or ligament facing to the joint, such as the joint surface of the annular ligament of the radius, were also positive for CA9. A distribution of each matrix components examined was not same as CA9. The bone-tendon and bone-ligament interface expressed CA9, but the duration at a site was limited to 3-4 weeks because the positive site was changed between stages. Thus, in the fetal entheses, CA9 expression displayed highly stage-dependent and site-dependent manners. CA9 in the fetal entheses seemed to play an additional role, but it was most likely to be useful as an excellent marker of mechanical stress at the start of enthesis development.
Aggrecans ; Anoxia ; Carbon* ; Carbonic Anhydrases* ; Cartilage ; Elastic Cartilage ; Fetal Development* ; Fetus ; Fibronectins ; Glial Fibrillary Acidic Protein ; Humans* ; Hydrogen-Ion Concentration ; Immunohistochemistry ; Intermediate Filaments ; Intervertebral Disc ; Joints* ; Ligaments* ; Pregnancy ; Radius ; Spine ; Stress, Mechanical* ; Tenascin ; Tendons* ; Versicans ; Zygapophyseal Joint

The human nervus terminalis (terminal nerve) and the nerves to the vomeronasal organ (VNON) are both associated with the olfactory nerves and are of major interest to embryologists. However, there is still limited knowledge on their topographical anatomy in the nasal septum and on the number and distribution of ganglion cells along and near the cribriform plate of the ethmoid bone. We observed serial or semiserial sections of 30 fetuses at 7–18 weeks (crown rump length [CRL], 25–160 mm). Calretinin and S100 protein staining demonstrated not only the terminal nerve along the anterior edge of the perpendicular lamina of the ethmoid, but also the VNON along the posterior edge of the lamina. The terminal nerve was composed of 1–2 nerve bundles that passed through the anterior end of the cribriform plate, whereas the VNON consisted of 2–3 bundles behind the olfactory nerves. The terminal nerve ran along and crossed the posterior side of the nasal branch of the anterior ethmoidal nerve. Multiple clusters of small ganglion cells were found on the lateral surfaces of the ethmoid's crista galli, which are likely the origin of both the terminal nerve and VNON. The ganglions along the crista galli were ball-like and 15–20 µm in diameter and, ranged from 40–153 in unilateral number according to our counting at 21-µm-interval except for one specimen (480 neurons; CRL, 137 mm). An effect of nerve degeneration with increasing age seemed to be masked by a remarkable individual difference.
Calbindin 2 ; Ethmoid Bone ; Fetus ; Ganglion Cysts ; Humans ; Individuality ; Masks ; Nasal Septum ; Nerve Degeneration ; Neurons ; Olfactory Nerve ; Vomeronasal Organ

Adult ; Colon ; Colon, Transverse ; Duodenum ; Fetus ; Gestational Age ; Humans ; Ileum ; Jejunum ; Logic ; Mesocolon ; Omentum ; Peritoneum ; Pyloric Antrum ; Pylorus ; Stomach ; Viscera

Adult ; Fetus ; Gestational Age ; Humans ; Maxilla ; Nasal Mucosa ; Palate ; Sutures