The Origin of the Variations of the Hyoid Apparatus in Human.

Currently, theories based on acquired calcification of the stylohyoid ligament are believed to be a pathogenesis of syndromes associated with the hyoid apparatus (HA) and its variations. We studied the development of the HA from Reichert´s cartilage using serial sections of 25 human embryos and 45 fetuses. We ensured a fact that, at the initial stage, the HA appeared as two independent cartilage segments, that is, the cranial or styloid segment and the caudal or hyoid segment of Reichert's cartilage, those are connected by a mesenchymal structure. However, between 8 and 10 weeks of development, the mesenchymal connection was lost. We hypothesize that this disconnection is likely to be one of the major factors to make a descent of the hyoid bone in evolution. The stylohyoid ligament was not observed. The variations of the HA, should be considered variations of the development of Reicherts cartilage. If these variations are maintained in the adult, are likely to explain a major symptom associated with Eagle's syndrome.

Origin of the torus mandibularis: an embryological hypothesis.

Torus mandibularis, a well-known protuberance in the dental field, has been defined as a hyperostosis in the lingual aspect of the body of the mandible above the mylohyoid line. However, the origin of the torus mandibularis has not yet been clarified. The aim of this study was to provide a better understanding on the origin of the torus in view of the specific development of Meckel's cartilage at the site corresponding to the adult torus. A total of 40 mid-term human fetuses at 7-16 weeks of gestation were examined. The 10-13 weeks stage corresponded to the critical period in which Meckel's cartilage with endochondral ossification underwent a bending at the beginning of the intramandibular course. At the level of mental foramen, which was located between the deciduous canine and the first deciduous molar germs, the medial lamina of the mandible protruded medially to reach Meckel's cartilage. Thus, the medial lamina covered the posterior and superior aspect of the bending Meckel's cartilage just above the attachment of the developing mylohyoid muscle (i.e., in the oral cavity). We considered a bony prominence, which composed the protruding medial lamina and the bending Meckel's cartilage as the fetal origin of the torus mandibularis. A new theory is proposed for the origin of the torus mandibularis based on the existence of an anlage formed during the development of the mandible, variable in morphology and size, but always constant.

Morphogenesis of the manubrium of sternum in human embryos: a new concept.

To revisit many theories on fetal development of the manubrium of the sternum, we examined 25 mid-term fetuses at 6-9 weeks of gestation. The initial developmental stage of the manubrium was characterized by a distinct interclavicular mesenchyme that was continuous with the developing clavicles. Because parts of the clavicle in which endochondral ossification occurs originate from the neural crest, the interclavicular mesenchyme seems to be of the same origin. The sternal bands, possibly of the lateral plate origin, were restricted at the anterior ends of the ribs in the paired thoracic walls. The interclavicular mesenchyme extended caudally and laterally to reach the anterior ends of the first ribs, and thus the interclavicular mesenchyme expanded into the intercostoclavicular mesenchyme. Then, the primitive manubrium was delimited by the sternoclavicular joint and its related ligaments, all of which developed from the interclavicular and intercostoclavicular mesenchymes. Although the first ribs were attached to the intercostoclavicular mesenchyme, the former was vimentin-negative in contrast to the latter, positive mesenchyme. Soon afterwards, the small upper end of the sternal bands was integrated into the intercostoclavicular mesenchyme to form the primitive manubrium. The infrahyoid muscles and their supplying nerves maintained a close topographical relation to the interclavicular or intercostoclavicular mesenchyme, whereas the pectoralis major muscle kept attachments to the sternal bands. Consequently, the manubrium of sternum appeared to develop in a complex way at a junction area between derivatives of the neural crest, lateral plate, and somite.

Initial stage of fetal development of the pharyngotympanic tube cartilage with special reference to muscle attachments to the tube.

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.

Human fetal hyoid body origin revisited.

The hyoid body is traditionally believed to have a dual origin from second and third arch mesenchyme, but this theory remains controversial. We examined paraffin-embedded sections from the hyoid region of 12 embryos and fetuses at 5-7 weeks of gestation (11-22 mm cranio-rump length). We found that the second (Reichert's cartilage) and third arch mesenchymal condensations did not reach the median area at the base of the tongue. Rather, a midline mesenchymal condensation was seen, and it separated from these arches at an early stage. This condensation was triangular and plate-like, and the cranial part was narrow between the bilateral Reichert's cartilages, while the caudal part was wide along the mediolateral axis between the bilateral primitive greater horns. We considered the midline mesenchymal condensation as the hyoid body anlage. At 7 weeks, a cartilaginous mass appeared in the midline condensation. The hypoglossal nerve changed its direction at the superolateral ends of the midline condensation. We propose that: (i) the hyoid body originates from the hypobranchial eminence via the midline condensation; (ii) the lesser horn originates from the caudal end of Reichert's cartilage; and (iii) the greater horn of the hyoid and the superior cornu of the thyroid cartilage originate from the third arch cartilage. The second and third arches may not regulate early hyoid body morphology.

Fetal topographical anatomy of the female urethra and descending vagina: a histological study of the early human fetal urethra.

BACKGROUND: Which parts of the male urethra correspond to the female urethra? To resolve this question, we need to understand fetal topographical changes in the urethra, its external sphincter and vagina. The vagina joins the mid-course of the primitive urethra and, later "descends" to the vaginal vestibulum. METHODS: We examined histological sections of 14 female and 4 male mid-term fetuses. RESULTS: The inferior end of the vagina was consistently embedded in the posterior wall of the urethra at 9-12 weeks. The supero-inferior level of the vaginal merging was lower in larger fetuses. Thus, the sequential variation in levels appeared to reflect the process of vaginal descent. However, in spite of penetration of the vaginal end into the posterior urethral wall, we found no sign of destruction of the urethral wall after vaginal descent in the low-merging types. Before vaginal descent, the female external sphincter extended posterolaterally around the urethra. CONCLUSION: The vaginal descent is classically regarded as a relative topographical change, but it is likely to be a result of elongation of the proximal urethra in the superior side of the vaginal merging. Conversely, the distal urethra is likely to be incorporated into the vaginal vestibulum by 15 weeks. During these processes, most of the female external sphincter seems to be expelled from the original anterior position into the vestibular wall as the urethrovaginal sphincter. The adult female urethra seems to correspond to the male prostatic urethra superior to the prostatic colliculus.

Early fetal development of the human cochlea.

The cochlear scalas are differentiated from a single tube with a lining by the tall epithelium, that is, the cochlear duct. However, we have no information about the mechanism involved in the formation of the scalas. We evaluated histological sections taken from 20 fetuses: eight each at 8--9 weeks [early stage; 28--45 mm crown-rump length (CRL)] and 11--12 weeks (middle stage; 52--74 mm CRL), and four at 14--15 weeks (late stage; 90--110 mm CRL) of gestation. In four of eight early-stage and in all eight middle-stage specimens, we observed irregular perilymphatic spaces and their fusion; these spaces tended to be larger in the future scala tympani than in the future scala vestibuli. The cochlear duct epithelium was positive for cytokeratin 19 in contrast to the other parts of the cochlea. The tectorial membrane appeared in two of eight middle-stage and all four late-stage specimens. After 16 weeks, mesothelial lining of the scala may follow the development of aquaporin-positive thin blood vessels along the scala wall. Notably, gap formation of the cochlear duct epithelium at a site facing the scala tympani consistently occurred before the development of S100 protein-negative organ of Corti. This gap is likely to correspond to a site occupied finally by Hensen's cells. All these steps likely started in the basal coil and extended to the apical side of the cochlea. These findings suggest that leakage through the epithelial gap of endolymph, with a high concentration of potassium ions, causes mesenchymal cell death, leading to the coalescence of vacuoles containing low potassium perilymph.

Closure of the middle ear with special reference to the development of the tegmen tympani of the temporal bone.

Closure of the middle ear is believed to be closely related to the evolutionary development of the mammalian jaw. However, few comprehensive descriptions are available on fetal development. We examined paraffin-embedded specimens of 20 mid-term human fetuses at 8-25 weeks of ovulation age (crown-rump length or CRL, 38-220 mm). After 9 weeks, the tympanic bone and the squamous part of the temporal bone, each of which was cranial or caudal to Meckel's cartilage, grew to close the lateral part of the tympanosquamosal fissure. At the same time, the cartilaginous tegmen tympani appeared independently of the petrous part of the temporal bone and resulted in the petrosquamosal fissure. Subsequently, the medial part of the tympanosquamosal fissure was closed by the descent of a cartilaginous inferior process of the tegmen tympani. When Meckel's cartilage changed into the sphenomandibular ligament and the anterior ligament of the malleus, the inferior process of the tegmen tympani interposed between the tympanic bone and the squamous part of the temporal bone, forming the petrotympanic fissure for the chorda tympani nerve and the discomalleolar ligament. Therefore, we hypothesize that, in accordance with the regression of Meckel's cartilage, the rapidly growing temporomandibular joint provided mechanical stress that accelerated the growth and descent of the inferior process of the tegmen tympani via the discomalleolar ligament. The usual diagram showing bony fissures around the tegmen tympani may overestimate the role of the tympanic bone in the fetal middle-ear closure.

Pleuroperitoneal canal closure and the fetal adrenal gland.

Pleuroperitoneal canal (PP canal) closure is generally considered to result from an increase in the height, and subsequent fusion, of the bilateral pleuroperitoneal folds (PP folds). However, the folds develop in the area ventral to the adrenal, in contrast to the final position of the diaphragm, which extends to the dorsal side of the adrenal (the "retro-adrenal" diaphragm). We examined the semiserial histology of 20 human embryos and fetuses (crown-rump length 11-40 mm). We started observations of the canal at the stage through which the lung bud extends far caudally along the dorsal body wall to the level of the future adrenal, and the phrenic nerve has already reached the PP fold. Subsequently, the developing adrenal causes narrowing of the dorsocaudal parts of the canal, and provides the bilateral midsagittal recesses or "false" bottoms of the pleural cavity. However, at this stage, the PP fold mesenchymal cells are still restricted to the ventral side of the adrenal, especially along the liver and esophagus. Thereafter, in accordance with ascent of the lung, possibly due to anchoring of the liver to the adrenal, the PP fold mesenchymal cells seem to migrate laterally along the coelomic mesothelium covering some sheet-like loose mesenchymal tissue behind the adrenal. Final closure of the PP canal by lateral migration to provide the "retro-adrenal" diaphragm is a process quite different from the common dogma. It is likely that the sheet-like loose mesenchymal tissue becomes the caudal part of the pleural cavity through a process involving cell death.

Venous drainage from the developing human base of mandible including Meckel's cartilage: the so-called Serres' vein revisited.

PURPOSE: The present study describes the venous drainage, especially, that via the so-called Serres' vein, from border areas between two different types of ossifications: the endochondral ossification of Meckel's cartilage in close topographical relation with the membranous ossification of the mandible. METHODS: Frontal and transverse sections of 25 human fetuses between 8 and 16 weeks of post-conception development. All sections were stained with hematoxylin, and eosin and azan. RESULTS: At 9 weeks, a distinct vein (Serres' vein) is seen originating from the endochondral ossification of Meckel's cartilage. At 11 weeks, the vein collects blood sinusoids from both the endochondral and membranous ossification areas. At 12 weeks the vein accompanies a definite bony canal, the Serres' canal. The vein does not extend anteriorly beyond a level of the deciduous canine germ that was located anterior to the mental foramen. Notably, up to 12 weeks, the vein becomes clearly isolated from the inferior alveolar nerve, artery, and vein. CONCLUSION: Serres' vein seems to be a unique drainage route of ossification, not of the tooth germ, and is similar to veins at the usual diaphysis of a long bone. Although the Serres' canal had been termed "canal of the deciduous dentition", there appears to be no topographical relation with deciduous germs.

Human orbital muscle: a new point of view from the fetal development of extraocular connective tissues.

PURPOSE: In the human body, the orbital muscle is a limited smooth-muscle tissue extending between hard tissues. To provide better understanding of its function, the authors re-examined its development in fetuses. METHODS: Using 20 human fetuses (12-25 weeks of gestation), semiserial horizontal or sagittal paraffin sections were prepared at intervals of 20 to 100 µm. In addition to routine histology, the authors performed silver staining as well as immunohistochemistry for alpha smooth-muscle actin (SMA), vimentin, S100 protein, and tyrosine hydroxylase. RESULTS: Up to 12 weeks, the orbital muscle appeared as a plate-like mesenchymal condensation between the ciliary and sphenopalatine ganglia. Up to 15 weeks, the thick smooth-muscle layer provided an inferoposterior wall for the orbit. A notable feature was a difference in fatty tissue development between the ocular (anterior) and posterior sides of the orbital muscle. At 20 and 25 weeks, SMA immunoreactivity and the amount of smooth-muscle basal lamina were decreased, in contrast to an increase in the number of collagenous fiber bundles. Nerves for the orbital muscle are unlikely to contain sympathetic fibers until 15 weeks. CONCLUSIONS: The authors hypothesize that, in the early stage, the orbital muscle separates the orbital content from the surrounding loose spaces to maintain conditions adequate for the development of orbital fat and other connective tissues. Later, the orbital muscle is replaced by collagenous fibers and seems to provide guidance for calcification of the inferoposterior bony orbital wall. Vimentin-positive osteoprogenitor cells appear to migrate from the perichondrium of the sphenoid and ethmoid.

Giant Aortic Arch Aneurysm and Cardio-vocal Syndrome: Still An Open-surgery Indication.

The Cardio-vocal Syndrome (Ortner's syndrome) is described as hoarseness due to the left recurrent laryngeal nerve palsy, caused by a specific cardiovascular pathology. In this case, we present a patient with a giant aortic arch aneurysm with an initial clinical presentation of Cardio-vocal Syndrome. The conventional open-surgery, instead of endovascular approach, was useful to control the morbidity from the compressive effect of adjacent structures, also preventing the aortic rupture. We strongly recommend analyzing carefully the individual case and the clinical targets to resolve, because the new technologies are not always the most effective therapeutic response.

Human primitive meninges in and around the mesencephalic flexure and particularly their topographical relation to cranial nerves.

Development of the meninges in and around the plica ventralis encephali has not been well documented. A distinct mesenchymal structure, the so-called plica ventralis encephali, is sandwiched by the fetal mesencephalic flexure. We histologically examined paraffin-embedded sections from 18 human embryos and fetuses at 6-12 weeks of gestation. In the loose tissues of the plica, the first meninx appeared as a narrow membrane along the oculomotor nerve at 7-8 weeks. Subsequently, the plica ventralis evolved into 3 parts: bilateral lateral mesenchymal condensations and a primitive membranous meninx extending between. Notably, the topographical anatomy of the oculomotor, trochlear and trigeminal nerves did not change: the oculomotor nerve ran along the rostral aspect of the membranous meninx, the trigeminal nerve ran along the caudal side of the lateral mesenchymal condensation, and the trochlear nerve remained embedded in the lateral condensation. Up to 9-10 weeks, the lateral mesenchymal condensations became tongue-like folds; i.e., the primitive form of the tentorium cerebelli, while the membranous meninx became the diaphragma sellae. The falx cerebri seemed to develop from the tongue-like folds. Overall, the final tentorium cerebelli corresponded to the regressed plica ventralis, while the parasellar area originated from the base of the plica and other tissues along the ventral aspects of the basisphenoid and basioccipital.