A term "mesoesophagus" has been often used by surgeons, but the morphology was not described well. To better understand the structures attaching the human abdominal and lower thoracic esophagus to the body wall, we examined serial or semiserial sections from 10 embryos and 9 fetuses. The esophagus was initially embedded in a large posterior mesenchymal tissue, which included the vertebral column and aorta. Below the tracheal bifurcation at the fifth week, the esophagus formed a mesentery-like structure, which we call the "mesoesophagus," that was sculpted by the enlarging lungs and pleural cavity. The pneumatoenteric recess of the pleuroperitoneal canal was observed in the lowest part of the mesoesophagus. At the seventh week, the mesoesophagus was divided into the upper long and lower short parts by the diaphragm. Near the esophageal hiatus, the pleural cavity provided 1 or 2 recesses in the upper side, while the fetal adrenal gland in the left side was attached to the lower side of the mesoesophagus. At the 10th and 18th week, the mesoesophagus remained along the lower thoracic esophagus, but the abdominal esophagus attached to the diaphragm instead of to the left adrenal. The mesoesophagus did not contain any blood vessels from the aorta and to the azygos vein. The posterior attachment of the abdominal esophagus seemed to develop to the major part of the phrenoesophageal membrane with modification from the increased mass of the left fetal adrenal. After postnatal degeneration of the fetal adrenal, the abdominal esophagus might again obtain a mesentery. Consequently, the mesoesophagus seemed to correspond to a small area containing the pulmonary ligament and aorta in adults.
Esophagus; Mesoesophagus; Pneumatoenteric recess; Phrenoesophageal membrane; Human embryo
In the embryonic heart, the primitive atrium is considered to receive the bilateral sinus horns including the upper terminal of the inferior vena cava (IVC). To reveal topographical anatomy of the embryonic venous pole of the heart, we examined horizontal serial paraffin sections of 15 human embryos with crown-rump length 9-31 mm, corresponding to a gestational age of 6-7 weeks or Carnegie stage 14-16. The IVC was often fixed to the developing right pulmonary vein by a mesentery-like fibrous tissue. Rather than the terminal portion of the future superior vena cava, the IVC contributed to form a right-sided atrial lumen at the stage. The sinus venosus or its left horn communicated with the IVC in earlier specimens, but in later specimens, the left atrium extended caudally to separate the sinus and IVC. In contrast, the right atrium consistently extended far caudally, even below the sinus horn, along the IVC. A small (or large) attachment between the left (or right) atrium and IVC in adult hearts seemed to be derived from the left (or right) sinus valve. This hypothesis did not contradict with the incorporation theory of the sinus valves into the atrial wall. Variations in topographical anatomy around the IVC, especially of the sinus valves, might not always depend on the stages but partly in individual differences.
Heart; Atrium; Inferior vena cava; Sinus venosus horn; Human embryo
Major histocompatibility complex class I (MHCI) molecules were recently identified as novel regulators of synaptic plasticity. These molecules are expressed in various brain areas, especially in regions undergoing activity-dependent synaptic plasticity, but their role in the nucleus accumbens (NAc) is unknown. In this study, we investigated the effects of genetic disruption of MHCI function, through deletion of β2-microblobulin, which causes lack of cell surface expression of MHCI. First, we confirmed that MHCI molecules are expressed in the NAc core in wild-type mice. Second, we performed electrophysiological recordings with NAc core slices from wild-type and β2-microglobulin knock-out mice lacking cell surface expression of MHCI. We found that low frequency stimulation induced long-term depression in wild-type but not knock-out mice, whereas high frequency stimulation induced long-term potentiation in both genotypes, with a larger magnitude in knock-out mice. Furthermore, we demonstrated that knock-out mice showed more persistent behavioral sensitization to cocaine, which is a NAc-related behavior. Using this model, we analyzed the density of total AMPA receptors and their subunits GluR1 and GluR2 in the NAc core, by SDS-digested freeze-fracture replica labeling. After repeated cocaine exposure, the density of GluR1 was increased, but there was no change in total AMPA receptors and GluR2 levels in wild-type mice. In contrast, following repeated cocaine exposure, increased densities of total AMPA receptors, GluR1 and GluR2 were observed in knock-out mice. These results indicate that functional deficiency of MHCI enhances synaptic potentiation, induced by electrical and pharmacological stimulation.
Detailed knowledge of the anatomy of the rhabdosphincter and adjacent tissues is mandatory during urologic surgery to ensure reliable oncologic and functional outcomes. To characterize the levator ani (LA) function for the urethral sphincter, we described connective tissue morphology between the LA and urethral rhabdosphincter. The interface tissue between the LA and rhabdosphincter area in males contained abundant irregularly arrayed elastic fibers and smooth muscles. The male rhabdosphincter was positioned alongside the LA to divide the elevation force and not in-series along the axis of LA contraction. The male perineal membrane was thin but solid and extends along the inferior margin or bottom of the rhabdosphincter area. In contrast, the female rhabdosphincter, including the compressor urethrae and urethrovaginal sphincter muscles, was embedded in the elastic fiber mesh that is continuous with the thick, multilaminar perineal membrane. The inferomedial edge of the female LA was attached to the upper surface of the perineal membrane and not directly attached to the rhabdosphincter. We presented new diagrams showing the gender differences in topographical anatomy of the LA and rhabdosphincter.
The mediobasal segment (S7) of the right lung has been considered to correspond to the cardiac lobe generally seen in mammals. To investigate fetal development of the right mediobasal segmental bronchus (B7), we examined paraffin-embedded serial sections of 15 embrynic and fetal lungs at 7-8 weeks (serial sections) as well as semiserial sections of 8 fetuses at 15-18 weeks (semiserial sections). All of the smaller specimens did not contain B7, but 2 of the 8 larger specimens carried B7: one was found in the immediately anterior side of the inferior pulmonary vein, while in the other, the subdivisions (B7a, B7b) were overriding the vein. Although the incidence might be underestimated because of observations using semiserial sections, the B7 was most likely to develop secondarily during a period from 8 to 15 weeks. Fetal topographical changes (mainly, the descent) of the middle lobe and the inferior pulmonary vein might relate with the secondarily budding of B7. The present result does not reduce a clinical relevance of B7 as a segmental bronchus of the lung segment system.
Lung segment; Right lower lobe; Mediobasal segment; Segmental bronchus VII; Human fetus
CD10, a marker of immature B lymphocytes, is expressed in the developing epithelium of mammary glands, hair follicles, and renal tubules of human fetuses. To assess mesenchymal and stromal expression of CD10, we performed immunohistochemical assays in whole body sections from eight fetuses of gestational ages 15-20 weeks. In addition to expression in urinary tract and intestinal epithelium, CD10 was strongly expressed at both gestational ages in fibrous tissues surrounding the airways from the larynx to lung alveoli, in the periosteum and ossification center, and in the glans of external genitalia. CD10 was not expressed, however, in other cavernous tissues. These findings suggest that mesenchymal, in addition to epithelial cells at specific sites, are likely to express CD10. The glomeruli, alveoli, and glans are all end products of budding or outgrowth processes in the epithelium or skin. However, in contrast to the CD34 marker of stromal stem cells, CD10 was not expressed in vascular progenitor cells and in differentiated vascular endothelium. The alternating pattern of CD10 and CD34 expression suggests that these factors play different roles in cellular differentiation and proliferation of the kidneys, airway and external genitalia.
CD10; Epithelium; Mesoderm; Human fetus
The paracolpium or paravaginal tissue is surrounded by the vaginal wall, the pubocervical fascia and the rectovaginal septum (Denonvilliers' fascia). To clarify the configuration of nerves and fasciae in and around the paracolpium, we examined histological sections of 10 elderly cadavers. The paracolpium contained the distal part of the pelvic autonomic nerve plexus and its branches: the cavernous nerve, the nerves to the urethra and the nerves to the internal anal sphincter (NIAS). The NIAS ran postero-inferiorly along the superior fascia of the levator ani muscle to reach the longitudinal muscle layer of the rectum. In two nulliparous and one multiparous women, the pubocervical fascia and the rectovaginal septum were distinct and connected with the superior fascia of the levator at the tendinous arch of the pelvic fasciae. In these three cadavers, the pelvic plexus and its distal branches were distributed almost evenly in the paracolpium and sandwiched by the pubocervical and Denonvilliers' fasciae. By contrast, in five multiparous women, these nerves were divided into the anterosuperior group (bladder detrusor nerves) and the postero-inferior group (NIAS, cavernous and urethral nerves) by the well-developed venous plexus in combination with the fragmented or unclear fasciae. Although the small number of specimens was a major limitation of this study, we hypothesized that, in combination with destruction of the basic fascial architecture due to vaginal delivery and aging, the pelvic plexus is likely to change from a sheet-like configuration to several bundles.
Pelvic nerve plexus; Rectovaginal septum; Denonvilliers' fascia; Internal anal sphincter; Pubocervical fascia
Although the pelvic autonomic plexus may be considered a mixture of sympathetic and parasympathetic nerves, little information on its composite fibers is available. Using 10 donated elderly cadavers, we investigated in detail the topohistology of nerve fibers in the posterior part of the periprostatic region in males and the infero-anterior part of the paracolpium in females. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were used as parasympathetic nerve markers, and tyrosine hydroxylase (TH) was used as a marker of sympathetic nerves. In the region examined, nNOS-positive nerves (containing nNOS-positive fibers) were consistently predominant numerically. All fibers positive for these markers appeared to be thin, unmyelinated fibers. Accordingly, the pelvic plexus branches were classified into 5 types: triple-positive mixed nerves (nNOS+, VIP+, TH+, thick myelinated fibers + or -); double-positive mixed nerves (nNOS+, VIP-, TH+, thick myelinated fibers + or -); nerves in arterial walls (nNOS-, VIP+, TH+, thick myelinated fibers-); non-parasympathetic nerves (nNOS-, VIP-, TH+, thick myelinated fibers + or -); (although rare) pure sensory nerve candidates (nNOS-, VIP-, TH-, thick myelinated fibers+). Triple-positive nerves were 5-6 times more numerous in the paracolpium than in the periprostatic region. Usually, the parasympathetic nerve fibers did not occupy a specific site in a nerve, and were intermingled with sympathetic fibers. This morphology might be the result of an "incidentally" adopted nerve fiber route, rather than a target-specific pathway.
Pelvic autonomic nerve plexus; Neuronal nitric oxide synthase; Vasoactive intestinal polypeptide; Tyrosine hydroxylase; Human anatomy
Using 5 fetuses of gestational age (GA) of 15-16 weeks and 4 of GA of 22–25 weeks, we examined site- and stage-dependent differences in CD68-positive microglial cell distribution in human fetal brains. CD68 positive cells were evident in the floor of the fourth ventricle and the pons and olive at 15-16 weeks, accumulating in and around the hippocampus at 22–25 weeks. At both stages, the accumulation of these cells was evident around the optic tract and the anterior limb of the internal capsule. When we compared CD68-positive cell distribution with the topographical anatomy of GAP43-positive developing axons, we found that positive axons were usually unaccompanied by CD68-positive cells, except in the transpontine corticofugal tract and the anterior limb of the internal capsule. Likewise, microglial cell distribution did not correspond with habenulointerpeduncular tract. Therefore, the distribution of CD68-positive cells during normal brain development may not reflect a supportive role of these microglia in axonogenesis of midterm human fetuses.
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.
Carbonic anhydrase type IX; Intermediate filaments; Joints; Enthesis; Human fetus
Using immunohistochemical staining for alpha-smooth muscle actin (α-SMA), glial fibrillary acidic protein (GFAP), S100 protein (S100), p63, cytokeratin 14 (CK14), and cytokeratin 19 (CK19), we studied acinar and myoepithelial cells of major and minor salivary glands obtained from 14 donated cadavers (78-92 years old) and 5 donated fetuses (aborted at 15-16 weeks of gestation). CK and p63 expression was investigated only in the adult specimens. SMA was detected in all adult glands as well as in fetal sublingual and pharyngeal glands. GFAP expression was seen in a limited number of cells in adult glands, but was highly expressed in fetal pharyngeal glands. S100-positive myoepithelial-like cells were present in adult minor glands as well as in fetal sublingual and pharyngeal glands. Expression of p63 was evident in the ducts of adult glands. CK14 immunoreactivity was observed in a limited number of glandular cells in adults, in contrast to consistent expression of CK19. In both adults and fetuses, a mosaic expression pattern was usually evident for each of the examined proteins. A difference in immunoreactivity for the nerve markers GFAP and S100 was observed between the major and minor glands. Thus, in the present histologic study, we distinguished between the specific gland types on the basis of their immunohistochemical staining. A mosaic expression pattern suggested that the immunoreactivity against nerve protein markers in myoepithelial cells could not be due to the persistence of neural crest remnants or the physiological status of the gland, such as age-related degeneration.
Salivary glands; Myoepithelial cells; Immunohistochemistry; Adult; Fetus
We examined pharyngeal nerve courses in paraffin-embedded sagittal sections from 10 human fetuses, at 25-35 weeks of gestation, by using S100 protein immunohistochemical analysis. After diverging from the glossopharyngeal and vagus nerves at the level of the hyoid bone, the pharyngeal nerves entered the constrictor pharyngis medius muscle, then turned upward and ran superiorly and medially through the constrictor pharyngis superior muscle, to reach either the levator veli palatini muscle or the palatopharyngeus muscle. None of the nerves showed a tendency to run along the posterior surface of the pharyngeal muscles. Therefore, the pharyngeal nerve plexus in adults may become established by exposure of the fetal intramuscular nerves to the posterior aspect of the pharyngeal wall because of muscle degeneration and the subsequent rearrangement of the topographical relationship between the muscles that occurs after birth.
Pharyngeal nerve plexus; Glossopharyngeal nerve; Constrictor pharyngis superior muscle; Levator veli palatini muscle; Human fetus
The supinator muscle originates from the annular ligament of the radius, and the muscle fibers and ligament take a similar winding course. Likewise, the coccygeus muscle and the sacrospinous ligament are attached together, and show a similar fiber orientation. During dissection of adult cadavers for our educational curriculum, we had the impression that these ligaments grow in combination with degeneration of parts of the muscles. In histological sections of 25 human fetuses at 10-32 weeks of gestation, we found that the proximal parts of the supinator muscle were embedded in collagenous tissue when the developing annular ligament of the radius joined the thick intermuscular connecting band extending between the extensor carpi radialis and anconeus muscles at 18-22 weeks of gestation, and the anterior parts of the coccygeus muscle were surrounded by collagenous tissue when the intramuscular tendon became the sacrospinous ligament at 28-32 weeks. Parts of these two muscles each seemed to provide a mold for the ligament, and finally became involved with it. This may be the first report to indicate that a growing ligament has potential to injure parts of the "mother muscle," and that this process may be involved in the initial development of the ligament.
Supinator muscle; Coccygeus muscle; Sacrospinous ligament; Annular ligament of the radius; Human fetus
It is still unclear whether the longitudinal anal muscles or conjoint longitudinal coats (CLCs) are attached to the vagina, although such an attachment, if present, would appear to make an important contribution to the integrated supportive system of the female pelvic floor.
Materials and Methods
Using immunohistochemistry for smooth muscle actin, we examined semiserial frontal sections of 1) eleven female late-stage fetuses at 28-37 weeks of gestation, 2) two female middle-stage fetus (2 specimens at 13 weeks), and, 3) six male fetuses at 12 and 37 weeks as a comparison of the morphology.
In late-stage female fetuses, the CLCs consistently (11/11) extended into the subcutaneous tissue along the vaginal vestibule on the anterior side of the external anal sphincter. Lateral to the CLCs, the external anal sphincter also extended anteriorly toward the vaginal side walls. The anterior part of the CLCs originated from the perimysium of the levator ani muscle without any contribution of the rectal longitudinal muscle layer. However, in 2 female middle-stage fetuses, smooth muscles along the vestibulum extended superiorly toward the levetor ani sling. In male fetuses, the CLCs were separated from another subcutaneous smooth muscle along the scrotal raphe (posterior parts of the dartos layer) by fatty tissue.
In terms of topographical anatomy, the female anterior CLCs are likely to correspond to the lateral extension of the perineal body (a bulky subcutaneous smooth muscle mass present in adult women), supporting the vaginal vestibule by transmission of force from the levator ani.
Anal canal; levator ani muscle; longitudinal anal muscle; rectum; smooth muscle; embryology
There is little or no information about the distribution of elastic fibers in the human fetal head. We examined this issue in 15 late-stage fetuses (crown-rump length, 220-320 mm) using aldehyde-fuchsin and elastica-Masson staining, and we used the arterial wall elastic laminae and external ear cartilages as positive staining controls. The posterior pharyngeal wall, as well as the ligaments connecting the laryngeal cartilages, contained abundant elastic fibers. In contrast with the sphenomandibular ligament and the temporomandibular joint disk, in which elastic fibers were partly present, the discomalleolar ligament and the fascial structures around the pterygoid muscles did not have any elastic fibers. In addition, the posterior marginal fascia of the prestyloid space did contain such fibers. Notably, in the middle ear, elastic fibers accumulated along the tendons of the tensor tympani and stapedius muscles and in the joint capsules of the ear ossicle articulations. Elastic fibers were not seen in any other muscle tendons or vertebral facet capsules in the head and neck. Despite being composed of smooth muscle, the orbitalis muscle did not contain any elastic fibers. The elastic fibers in the sphenomandibular ligament seemed to correspond to an intermediate step of development between Meckel's cartilage and the final ligament. Overall, there seemed to be a mini-version of elastic fiber distribution compared to that in adults and a different specific developmental pattern of connective tissues. The latter morphology might be a result of an adaptation to hypoxic conditions during development.
Elastic fibers; Sphenomandibular ligament; Ear ossicles; Head; Human fetus
We examined a series of changes that occur in the trabecular meshwork fibers of human eyes during fetal development at 12-30 weeks of gestation. At 12 and 15 weeks, the uveal meshwork was stained black with silver impregnation (indicating the predominance of collagen types III and IV) in the endomysium of the ciliary muscle. At 20 weeks, in combination with Schlemm's canal, a dense fibrous tissue mass corresponding to the trabecular meshwork anlage appeared and was colored black. The anlage was continuous with the corneal endothelium rather than with the ciliary muscle. Until 25 weeks, the trabecular meshwork was identifiable as fragmented fiber bundles that stained red-black, suggesting a mixture of collagen types I, III, and IV. At 30 weeks, half of the ciliary muscle fibers were inserted into the scleral spur and not into the meshwork. Therefore, any contribution of ciliary muscle contraction to the differentiation of the trabecular meshwork would appear to be limited. We hypothesize that an uneven distribution of mechanical stresses in the area of the cornea-sclera junction causes a tear thereby creating Schlemm's canal and is accompanied by a change in the collagen fiber types comprising the meshwork.
Trabecular meshwork; Schlemm's canal; Collagen; Silver staining
Connexin-43, a major gap junction protein, and cytokeratin-19, one of the intermediate filament keratins, are known to be markers of well-differentiated epithelium. In this study, we investigated the expression of these markers in the head region, lungs, and abdominal organs of 10 human mid-term fetuses. The expression of connexin-43 was found to be restricted to the dura mater, kidney, and adrenal cortex. In the kidney, we found a clear site-dependent difference in the expression pattern of these markers: connexin-43 expression was observed in the tubules of the renal cortex whereas cytokeratin-19 was strongly expressed in the collecting ducts and renal pelvis. This difference remained unchanged throughout the fetal stages examined. Immunoreactivity was not observed for either of the markers in the intrarenal vessels, including the glomeruli, and mesangial cells. Connexin-43 expression seemed to be restricted to the metanephric vesicle-derived structures that differentiate in the urogenital ridge of the splanchnic mesoderm. The adrenal cortex also originates from the same para-aortic mesoderm. In contrast, in the urogenital organs, cytokeratin-19 seemed to be expressed in ducts derived from the urogenital sinus.
Connexin-43; Cytokeratin-19; Kidney; Immunohistochemistry; Human fetus
Synaptic plasticity of the female hippocampus may cyclically fluctuate across the estrous cycle. The spine density fluctuation had been explained by fluctuation of plasma estradiol (E2) and progesterone (PROG), with the assumption that these steroids penetrate into the hippocampus. Recently, however, we demonstrated that male hippocampal levels of sex steroids are much higher than those in plasma, suggesting a weak contribution of plasma steroids to the spine density. By combination of mass-spectrometric analysis with HPLC-purification and picolinoyl-derivatization of hippocampal sex steroids, we determined the accurate concentration of E2 and PROG at four stages of plasma estrous cycle including Proestrus (Pro), Estrus (Est), Diestrus 1 (D1), and Diestrus 2 (D2). Hippocampal levels of E2 and PROG showed cyclic fluctuation with a peak at Pro for E2 and at D1 for PROG, having a positive correlation with the plasma estrous cycle. All these sex steroid levels are much higher in the hippocampus than in plasma. Even after ovariectomy a significant levels of E2 and PROG were observed in the hippocampus. The total spine density showed higher values at Pro and D1, and lower values at Est and D2, having a good correlation with the peak levels of hippocampal E2 or PROG. We also examined fluctuation of the head diameter of spines. Interestingly, mRNA expression level of steroidogenic enzymes (P450arom and 17β-HSD, etc.) and sex-steroid receptors did not significantly change across the estrous cycle. Therefore, the fluctuation of total hippocampal PROG (equal to sum of hippocampus-synthesized PROG and plasma PROG) may be originated from the contribution of cyclic change in plasma PROG, which can induce the fluctuation of total hippocampal E2, since steroid conversion activity of hippocampus might be nearly the same across the estrus cycle.
hippocampus-synthesized steroids; estradiol; dendritic spines; estrous cycle; progesterone
Modulation of synapses under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. We tried to test whether rapid CORT effects involve activation of essential kinases as non-genomic processes. We demonstrated rapid effects (~1 h) of CORT on the density of thorns, by imaging Lucifer Yellow-injected neurons in adult male rat hippocampal slices. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. The application of CORT at 100, 500, and 1000 nM induced a rapid increase in the density of thorns in the stratum lucidum of CA3 pyramidal neurons. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, including MAPK, PKA, or PKC, suppressed CORT-induced enhancement of thorn-genesis. On the other hand, GSK-3β was not involved in the signaling of thorn-genesis. Blocking AMPA receptors suppressed the CORT effect. Expression of CA3 synaptic/extranuclear GR was demonstrated by immunogold electron microscopic analysis. From these results, stress levels of CORT (100–1000 nM) might drive the rapid thorn-genesis via synaptic/extranuclear GR and multiple kinase pathways, although a role of nuclear GRs cannot be completely excluded.
corticosterone; hippocampus; kinase; thorn; stress; spine
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.
CD68-positive macrophages; Hand and foot; Lymphatic vessels; Enthesis; Human fetus
Although the rectus abdominis and its sheath are well known structures, their development in the human fetus is poorly understood.
Materials and Methods
We examined rectus abdominis and sheath development in semiserial horizontal sections of 18 fetuses at 5-9 weeks of gestation.
Rectus muscle differentiation was found to commence above the umbilicus at 6 weeks and extend inferiorly. Until closure of the anterior chest wall via fusion of the bilateral sternal anlagen (at 7 weeks), the anterior rectal sheath originated from the external oblique and developed towards the medial margin of the rectus abdominis at all levels, including the supracostal part. After formation of the anterior sheath, fascial laminae from the internal oblique and transversus abdominis contributed to formation of the posterior rectus sheath. However, the posterior sheath was absent along the supracostal part of the rectus abdominis, as the transversus muscle fibers reached the sternum or the midline area. Therefore, it appeared that resolution of the physiological umbilical hernia (8-9 weeks) as well as chest wall closure was not required for development of the rectus abdominis and its sheath. Conversely, in the inferior part of the two largest fetal specimens, after resolution of the hernia, the posterior sheath underwent secondary disappearance, possibly due to changes in mechanical stress.
Upward extension of the rectus abdominis suddenly stopped at the margin of the inferiorly developing pectoralis major without facing the external intercostalis. The rectus thoracis, if present, might correspond to the pectoralis.
Rectus abdominis; rectus sheath; pectoralis; sternalis; sternum; rib
Fetal development of the cartilage of the pharyngotympanic tube (PTT) is characterized by its late start. We examined semiserial histological sections of 20 human fetuses at 14-18 weeks of gestation. As controls, we also observed sections of 5 large fetuses at around 30 weeks. At and around 14 weeks, the tubal cartilage first appeared in the posterior side of the pharyngeal opening of the PTT. The levator veli palatini muscle used a mucosal fold containing the initial cartilage for its downward path to the palate. Moreover, the cartilage is a limited hard attachment for the muscle. Therefore, the PTT and its cartilage seemed to play a critical role in early development of levator veli muscle. In contrast, the cartilage developed so that it extended laterally, along a fascia-like structure that connected with the tensor tympani muscle. This muscle appeared to exert mechanical stress on the initial cartilage. The internal carotid artery was exposed to a loose tissue facing the tubal cartilage. In large fetuses, this loose tissue was occupied by an inferior extension of the temporal bone to cover the artery. This later-developing anterior wall of the carotid canal provided the final bony origin of the levator veli palatini muscle. The tubal cartilage seemed to determine the anterior and inferior margins of the canal. Consequently, the tubal cartilage development seemed to be accelerated by a surrounding muscle, and conversely, the cartilage was likely to determine the other muscular and bony structures.
Pharyngotympanic tube cartilage; Levator veli palatini muscle; Internal carotid artery; Tensor tympani muscle; Human fetuses
We recently demonstrated the morphology of the anococcygeal ligament. As the anococcygeal ligament and raphe are often confused, the concept of the anococcygeal raphe needs to be re-examined from the perspective of fetal development, as well as in terms of adult morphology.
Materials and Methods
We examined the horizontal sections of 15 fetuses as well as adult histology. From cadavers, we obtained an almost cubic tissue mass containing the dorsal wall of the anorectum, the coccyx and the covering skin. Most sections were stained with hematoxylin and eosin or Masson-trichrome solution.
The adult ligament contained both smooth and striated muscle fibers. A similar band-like structure was seen in fetuses, containing: 1) smooth muscle fibers originating from the longitudinal muscle coat of the anal canal and 2) striated muscle fibers from the external anal sphincter (EAS). However, in fetuses, the levator ani muscle did not attach to either the band or the coccyx. Along and around the anococcygeal ligament, we did not find any aponeurotic tissue with transversely oriented fibers connecting bilateral levator ani slings. Instead, in adults, a fibrous tissue mass was located at a gap between bilateral levator ani slings; this site corresponded to the dorsal side of the ligament and the EAS in the immediately deep side of the natal skin cleft.
We hypothesize that a classically described raphe corresponds to the specific subcutaneous tissue on the superficial or dorsal side of the anococcygeal ligament.
Anal canal; rectum; smooth muscle; embryology; anatomy; histology
To investigate why the development of a completely circular striated sphincter is so rare, we examined histological sections of 11 female and 11 male mid-term human fetuses. In male fetuses, the striated muscle initially extended in the frontal, rather than in the horizontal plane. However, a knee-like portion was absent in the female fetal urethra because, on the inferior side of the vaginal end, a wide groove for the future vestibule opened inferiorly. Accordingly, it was difficult for the developing striated muscle to surround the groove, even though there was not a great difference in width or thickness between the female vestibule and the male urethra. The development of a completely circular striated sphincter seems to be impossible in females because of interruption of the frontal plane by the groove-like vestibule. However, we cannot rule out the possibility that before descent of the vagina, the urethral striated muscle extends posteriorly.
Urethal rhabdosphincter; Genital tract; Urogenital sinus; Colliculus; Human fetus
Modulation of dendritic spines under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus.
Here we demonstrated the mechanisms of rapid effect (∼1 h) of CORT on the density and morphology of spines by imaging neurons in adult male rat hippocampal slices. The application of CORT at 100–1000 nM induced a rapid increase in the density of spines of CA1 pyramidal neurons. The density of small-head spines (0.2–0.4 µm) was increased even at low CORT levels (100–200 nM). The density of middle-head spines (0.4–0.5 µm) was increased at high CORT levels between 400–1000 nM. The density of large-head spines (0.5–1.0 µm) was increased only at 1000 nM CORT. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, such as MAPK, PKA, PKC or PI3K, suppressed CORT-induced enhancement of spinogenesis. Blocking NMDA receptors suppressed the CORT effect.
These results imply that stress levels of CORT (100–1000 nM) drive the spinogenesis via synaptic GR and multiple kinase pathways.