Article Topography of the inferior in human embryos and fetuses. An histomorphological study. Sergey Lvovich Kabak, 1 Natallia Victorovna Zhuravleva1 & Yuliya Michailovna Melnichenko.1 Affiliations: 1Human Morphology Depart- Abstract: The aim of this study is to establish the position of the inferior ment, Belarusian State Medical University, alveolar nerve in relation to the Meckel’s cartilage, the anlage of the Minsk, Belarus. mandibular body and primordia of the teeth, and also to trace the change in nerve trunk structure in the human prenatal ontogenesis. Serial sections Corresponding author: Yuliya Michailovna (20µm) from thirty-two 6-12 weeks-old entire human embryos and serial Melnichenko. Human Morphology Depart- ment, Belarusian State Medical University, sections (10µm) of six of 13-20 weeks-old human fetuses without Dzerzhinskogo Avenue 83, Minsk, Belarus. Phone: developmental abnormalities were studied. Histological sections were (375)291637867. Email: [email protected] impregnated with silver nitrate according to Bilshovsky-Buke and stained with hematoxylin and eosin. During embryonic development, the number of branches of the increases and its fascicular structure Receipt: 10/06/2017 Revised: 10/26/2017 changes. In conclusion, the architecture of intraosseous canals in the body Acceptance: 11/30/2017 Online: 11/30/2017 of the , as well as the location of the foramina, is predetermined by the course and pattern of the vessel/nerve branching in the mandibular arch, even before the formation of bony trabeculae. Particularly, the formation of the incisive canal of the mandible can be explained by the presence of the incisive nerve as the extension of the inferior alveolar nerve. It has also been established that Meckel’s cartilage does not participate in morphogenesis. Keywords: ; mandible; embryo research.

INTRODUCTION.

Conflict of interests: The authors declare no The inferior alveolar nerve is one of the terminal branches of conflict of interest. the mandibular nerve. After exiting the cranium through foramen ovale, it lies posterior and lateral to ; then it enters the Ethics approval: The present study was approved by the Medical Ethics Committee mandibular canal, in which it is accompanied by the artery and vein of the Belarusian State Medical University, of the same name, as well as lymphatic vessels.1 The branches of the Minsk, Belarus (Protocol No.: 2017/2). inferior alveolar nerve are the and the Funding: None. that along with the dental branches form the . The mylohyoid nerve and the mental nerve are located outside the Authors’ contributions: This work was carried out mandible, whereas the dental branches originate in the bone. in collaboration between all authors. All authors read and approved the final manuscript. According to the literature there are several types of branching of the inferior alveolar nerve inside the bone.2 In most of the cases it is Acknowledgements: None. one thick trunk, which splits into two terminal branches in the region Cite as: Kabak SL, Zhuravleva NV & of the : the mental and incisive nerves. The branches Melnichenko YM. Topography of the inferior innervating lower molars and the second premolar start from the alveolar nerve in human embryos and fetuses. An histomorphological study. J Oral Res 2017; inferior alveolar nerve before branching into its terminal subdivisions. 6(11):291-298. doi:10.17126/joralres.2017.082 Mandibular receive innervation from the incisive nerve, or the ISSN Online 0719-2479 - www.joralres.com © 2017 291 Kabak SL, Zhuravleva NV & Melnichenko YM. Topography of the inferior alveolar nerve in human embryos and fetuses. An histomorphological study. J Oral Res 2017; 6(11):291-298. doi:10.17126/joralres.2017.082 incisive plexus can be formed instead. In many cases, primordia of the teeth, and to trace the change in nerve the terminal branches of the inferior alveolar nerve trunk structure in human prenatal ontogenesis. can be surrounded by their own perineurium and lie separately from the beginning of the mandibular MATERIALS AND METHODS. canal.3 In such case, the incisive nerve, consisting Serial sections (20µm) from 32 entire human embryos of three or four bundles of nerve fibers, spreads its and fetuses without developmental abnormalities (6-12 branches to dental alveoli. weeks of gestation, 13-70mm of crown-rump length Various aspects of the human prenatal morphogenesis [CRL]) impregnated with silver nitrate according to of the mandible, such as histogenesis of bone tissue and Bilshovsky-Buke and stained with hematoxylin and the role of Meckel’s cartilage, have been previously eosin were studied. discussed by some authors.4-6 Evidence about the position All samples were taken from the collection of the of the inferior alveolar nerve inside the mandible in the Belarusian State Medical University. In addition, process of its embryonic development is scarce. mandibles from six fetuses without developmental These data are necessary to explain the origin of an abnormalities (13-20 weeks of gestation) were cut into additional mental foramen, as well as the presence of 3-4 pieces which were used for making serial transverse, individual alterations in anatomy of the mandibular frontal and sagittal histological sections (10µm) stained canal containing the inferior alveolar nerve. This canal with hematoxylin and eosin. can bifurcate or have lateral branches that are well Age of human embryos and fetuses was determined visualized in vivo when studied with the use of modern by the crown-rump length or obstetric anamnesis radiographic techniques.7,8 (Table 1). The aim of the study is to establish the position of The present study was approved by the Medical the inferior alveolar nerve in relation to the Meckel’s Ethics Committee of the Belarusian State Medical cartilage, the anlage of the mandibular body and University, Minsk, Belarus (Protocol No.: 2017/2).

Table 1. Embryos and fetuses used for this study.

Size (CRL, mm) Embryonal age (days or weeks) Number of embryos 13 44 days 1 17 44 days 6 22 51 days 4 23 54 days 7 24 54 days 5 27 56,5 days 3 33 10+1 weeks 3 34 10+2 weeks 3 - 13 weeks ◊◊ 1 - 14 weeks◊◊ 1 - 16 weeks ◊◊ 1 - 20 weeks◊◊ 3

◊◊ Gestational age.

292 ISSN Online 0719-2479 - www.joralres.com © 2017 Kabak SL, Zhuravleva NV & Melnichenko YM. Topography of the inferior alveolar nerve in human embryos and fetuses. An histomorphological study. J Oral Res 2017; 6(11):291-298. doi:10.17126/joralres.2017.082

RESULTS. ossification spreads radially, and at the end of the In 13mm (CRL) human embryos, a Meckel’s cartilage embryonic and early fetal periods the anlage of anlage is found in the form of a small condensation mandibular body consists of lateral and medial bone of mesenchymal cells within the mandibular processes plates. They partially merge, resulting in the formation (Figure 1A). The anlage is located near the inferior of a Y-shaped structure, which covers the lower part of alveolar nerve, which is almost twice as large as its the inferior alveolar nerve below by forming a groove. cross-sectional area and is a direct continuation of the In 22-24mm (CRL) human embryos, the terminal mandibular nerve, originating from the trigeminal branches of the inferior alveolar nerve are revealed. ganglion. The ganglion is a cluster of rounded neurons They are located on both sides of the lateral bone plate. near the ventral surface of the neural tube. The branches Nerve fibers within the mental nerve are convoluted, exiting the ganglion lie in the same plane and can be loosely packed, but run parallel to each other. In one clearly identified in the direction of their course. embryo with a CRL of 24mm the incisive nerve consists The mandibular nerve is the largest branch of the of loosely connected convoluted nerve fibers. In another and consists of thin, convoluted, embryo (23-mm CRL) it is a compact trunk that divides loosely packed nerve fibers forming one bundle. The into lateral branches from several nerve fibers towards distal end of the mandibular nerve is divided into the the dental lamina. In an embryo with a CRL of 27mm, inferior alveolar and the lingual nerve. The inferior the inferior alveolar nerve, lying between the two bone alveolar nerve is composed of loosely arranged nerve plates (outside the Meckel’s cartilage), is characterized fibers and can be seen in the mandibular process to by a compact arrangement of nerve fibers that are a considerable extent. Nerve divisions into secondary forming one bundle (Figure 1C). Lateral branches of branches have not been identified. the nerve are not revealed. In 17mm (CRL) human embryos, outside of Meckel’s In the fetuses with a CRL of 33-34mm the lateral cartilage within mesenchyme of the mandibular dental branches extending from the inferior alveolar 2 processes, the primary center of ossification can be nerve first run parallel to the main trunk and then 10 follow towards the tooth germ (Figure 2A). The identified (Figure 1B). Initially, it has the shape of a 1 9 plate, which is located laterally from the Meckel’s lateral plate retains a wide gap3 (the area of the future 5 cartilage and is separated from it by the inferior alveolar mental foramen). At this point, the4 major part of the nerve. Subsequently, the process of intramembranous nerve fibers of the inferior alveolar nerve are8 turned 5 7 Figure 1. Topography of trigeminal nerve and its branches in 11 human embryos of 13mm CRL (A), 17mm CRL (B) and 27mmA CRL (C). 6 B

Figure 1. Topography of trigeminal nerve and its branches in human embryos of 13mm CRL (A), 17mm CRL (B) and 27mm CRL (C). 2 2 1. Trigeminal ganglion. 2. . 3. Maxillary 1010 12 nerve. 4. Mandibular nerve. 5. Inferior alveolar nerve. 6. 13 9 9 Meckel’s cartilage anlage. 7. Facial nerve. 8. 11 Vestibulocochlear nerve. 9. Neural tube. 10. Meckel’s 3 3 cartilage. 11. Primary center of ossification. 12. . 5 5 4 4 5 13. Lateral palatine shelf. 14. Lateral and medial plates of mandibular body anlage. 15. Hyoid bone anlage. 16. 8 8 16 Hyoglossus muscle. 5 5 Sagittal (A) and frontal (C) sections impregnated with 7 7 10 8 1111 15 silver nitrate according to Bilshovsky-Buke. Sagittal A B C section (B) stained with H&E. AA 6 6 BB C 14 8 Magnification, (A) x100; (B) x200; (C) x40.

1. Trigeminal ganglion. 2. Ophthalmic nerve. 3. MaxillaryFigureFigure 1. nerve.1. Topography Topography 4. Mandibular of of trigem trigem inalnerve.inal nerve nerve 5. Inferior and and its its branches alveolar branches nerve. 6. Meckel’s cartilage anlage. 7. Facial nerve. 8. Vestibulocochlear nerve. 9. Neural tube.in 10. inhuman human Meckel’s embryos embryos cartilage. of of 13mm 13mm 11. PrimaryCRL CRL (A), (A), center 17mm 17mm ofCRL CRL ossification. (B) (B) and and 12. Tongue. 13. Lateral palatine shelf. 14. Lateral and medial plates of mandibular body anlage.27mm27mm CRL15. CRL Hyoid (C). (C). bone anlage. 16. Hyoglossus muscle. Sagittal (A) and frontal (C) sections impregnated1212 1. with1. Trigeminal Trigeminal silver nitrate ganglion. ganglion. according 2. 2. Ophthalmic Ophthalmic to Bilshovsky-Buke. nerve. nerve. 3. 3. Maxillary Maxillary Sagittal section (B) stained with H&E. nerve.nerve. 4. 4.Mandibular Mandibular nerve. nerve. 5. 5. Inferior Inferior alveolar alveolar nerve. nerve. 6. 6. 1313 Meckel’sMeckel’s cartilagecartilage anlage.anlage. 7.7. FacialFacial nerve.nerve. 8. 8. Magnification, (A) x100; (B) x200; (C) x40. VestibulocVestibulocochlearochlear nerve. nerve. 9 . 9.Neural Neural tube. tube. 10. 10. M eckel’sMeckel’s cartilage.cartilage. 11 11. Primary. Primary center center of of ossification. ossification. 1 21.2 Tongue.. Tongue. ISSN Online 0719-24795 5 - www.joralres.com © 2017 131.3 Lateral. Lateral palatine palatine shel shelf. 1f.4 1.4 Lateral. Lateral and and medial medial plates plates of of 293 mandibularmandibular body body anlage. anlage. 1 51.5 .Hyoid Hyoid bone bone anlage. anlage. 1 61. 6. 1616 HyoglossusHyoglossus muscle. muscle. 8 8 SagittalSagittal (A (A) )and and frontal frontal (C) (C) sections sections impregnated impregnated with with 1010 silversilver nitrate nitrate according according to toBilshovsky Bilshovsky-Buke.-Buke. Sagittal Sagittal 1515 sectionsection (B) (B) stained stained with with H&E. H&E. CC 1414 8 8 MagnMagnification,ification, (A ()A x100;) x100; (B ()B x200;) x200; (C ()C x40.) x40.

3 4 3

3 4 2 3 5 2 2 Kabak SL, Zhuravleva6 NV & Melnichenko YM. Topography of the inferior 2alveolar nerve1 in human embryos and5 fetuses. An histomorphological study. J Oral Res 2017; 6(11):291-298.6 doi:10.17126/joralres.2017.0826 4 1 5 8 6 4 Figure 2. Inferior alveolar nerve and its branches in humanA embryo of 33mm CRL at the level5 of7 the posterior8 tooth germ (A), the mental foramen (B), the mental symphysisA (C) and at the level of the anteriorB tooth7 germ (D).

B 3 4 3 4 3 3 2 2 2 5 2 5 6 9 3 9 1 6 4 9 5 3 9 1 6 4 5 6 8 4 44 5 8 22 A 7 4 46 AA B 7 C CC DD 4 4 B 1. Inferior alveolar nerve. 2. Dental branch.2 3. Tooth3 germ. 4. Meckel’sFigure cartilage.Figure 2.Inferior 2.Inferior 5. alveolar Mental alveolar nerve nerve nerve and andbranch. its itsbranches branches 6. Mental in in human human foramen. embryoembryo8 ofof 7. 33mm33mm Lateral CRL CRL plateat atthe the of mandibular body. 8. Medial plate of mandibular body. 9. Incisive nerve.level oflevel the ofposterior the posterior tooth tooth germ germ (A), (A), the the mental mental foramen foramen (B), (B), thethe mentalmental symphysis symphysis (C) (C) and atand the atlevel the oflevel the of anterior the anterior tooth tooth germ germ (D) (D) Sagittal sections impregnated with silver nitrate according to Bilshovsky-Buke.1. Inferior alveolar nerve. 2. Dental branch. 3. Tooth germ. 4. Meckel’s cartilage. 5. 1. Inferior alveolar nerve. 2. Dental branch. 3. Tooth germ. 4. Meckel’s cartilage. 5. Magnification, (A-D) x200. Mental nerve branch.5 6. Mental7 foramen. 7. Lateral plate of mandibular body. 8. Medial Mentalplate nerve of mandibularbranch. 6. body.Mental 9. foramen.Incisive nerve. 7. Lateral plate of mandibular body. 8. Medial 2 plate ofSagittal mandibular sections body. impregnated 9. Incisive with nerve. silver nitrate according to Bilshovsky-Buke. Figure 3. Topography of the inferiorSagittal alveolarMagnification, sections nerve impregnated (A- D)and x200. its with branches silver nitrate in according human to Bilshovsky-Buke. 9 Magnification, (A-D) x200. 3 fetuses of 163 weeks (A) and9 13 weeks B(B, C) of gestation. 9 5 4 3 9 4 5 2 4 4 4 4C 6 D 5 4 3 2 Figure2 2.Inferior alveolar nerve4 and its branches in human8 embryo of 33mm CRL at the Clevel of the posterior tooth germ (A),5 the7 mental foramenD (B), the mental symphysis (C) 4 and 2at the level of the anterior tooth germ 6(D) 1. Inferior alveolar nerve. 2. DentalB branch. 3. Tooth germ. 4. Meckel’s cartilage. 5. FigureMental3 2.Inferior nerve b5ranch. alveolar 6. Mental nerve foramen. and its branches 7. Lateral platein human of mandibular embryo body.of 33mm 8. Medial CRL at the plate of mandibular body. 9. Incisive nerve. 3 level4 of the posterior tooth germ (A), the mental foramen (B), the mental symphysis (C) 2 andSagittal at the sections level of impregnated the anterior with tooth silver germ nitrate (D) according to Bilshovsky-Buke.8 Magnification, (A-D) x200. 1. Inferior alveolar nerve. 2. Dental branch. 3. Tooth germ. 4. Meckel’s cartilage. 5. Mental nerve branch. 6. Mental foramen.5 7.7 Lateral plate of mandibular body. 8. Medial 9 7 plate of mandibular body. 9. Incisive nerve. 8 Sagittal sections impregnated with silver1 nitrate according to Bilshovsky-Buke. 1 2 9 7 1 AMagnification,1 (A-D) x200. B 8 C 3 A ABC C 5 D Figure 3.Topography of the inferior alveolar nerve and its branches in human fetuses of 16 weeks (A) and 13 weeks (B, C) of gestation. B 1.1. Inferior alveolar alveolar nerve. 2. Mental nerve. nerve branches. Figure2. Mental 3. Mental 3.Topography nerve foramen. 4.branches. Lateral plate of of 3. theMental inferior foramen. alveolar 4. Lateral nerve plate and of mandibular its branches body inanlage. human 5. Incisive fetuses nerve. of 166. Bone 4 trabecula.mandibular body 7.anlage. Dental 5. Incisive branch. nerve. 6. Bone 8. Toothtrabecula. 7.germ. Dental branch. 9. Dental 8. Tooth plexus. 4 germ. 9. Dental plexus. weeks (A) and 13 weeks (B, C) of gestation. SagittalSagittal sections sections of mandible, of stained mandible, with H&E. stained with H&E. 4 5 Magnification, (A) x40; (B,C) x100. 1. Inferior alveolar nerve. 2. Mental nerve branches. 3. Mental foramen. 4. Lateral plate of Magnification, (A) x40; (B,C) x100. 2 6 mandibular body anlage. 5. Incisive nerve. 6. Bone trabecula. 7. Dental branch. 8. Tooth 2 germ. 9. Dental plexus. 3 Figure 4. Neurovascular bundle of mandible in 20-week-old fetuses at the level 3 Sagittal sectionsof posterior of mandible, tooth germs stained (A-D) andwith mandibular H&E. foramen (E,F). A B C Magnification, (A) x40; (B,C) x100. D Figure 4. Neurovascular bundle of 9 7 mandible in 20-week-old fetuses at the 8 1 level of posterior tooth germs (A-D) and 1 1 10 11 11 (E,F). A C 1. Tooth germ. 2. Mental nerve. 3. Incisive nerve. 4. Serre’s’ vein in the separate 4 D osseous canal. 5. Dental branches of the Figure 3.Topography of the inferior alveolar nerve and its branches in human fetuses ofD 16 BB inferior alveolar nerve. 6. Inferior alveolar weeks (A) and 13 weeks (B, C) of gestation. 4 4 artery.7. Inferior alveolar nerve. 8. Lingual 1. Inferior alveolar nerve. 2. Mental nerve branches. 3. Mental foramen. 4. Lateral plate of nerve. 9. Mylohyoid nerve. 10. Mandibular 4 5 condylar cartilage. 11. Membranous part mandibular body anlage. 5. Incisive4 nerve. 6. Bone trabecula. 7. Dental branch. 8. Tooth 5 8 6 of mandible. germ. 9. Dental plexus. 2 2 6 2 2 6 Sagittal sections of mandible, stained with Sagittal sections of mandible, stained with H&E. H&E. Magnification, (A) x40; (B,C) x100. 3 F Magnification, (A,C,E) x40; (B,D,F) x100. 3 3 7 9 3 A B 11 A BB C DD EE FF A C D Figure 4. Neurovascular bundle of 1. Tooth germ. 2. Mental nerve. 3. Incisive nerve. 4. Serre’s’Figure vein in the4. separateNeurovascular osseous canal.bundle 5. Dentalof branches of the inferior alveolar nerve. 6. .7. Inferior alveolar nerve. 8. Lingualmandible nerve. in 9. 20Mylohyoid-week-old nerve. fetuses 10. Mandibularat the condylar cartilage. 11. Membranous part levelmandible of posterior in 20 tooth-week germs-old fetuses (A-D) and at the of mandible. 10 level of posterior tooth germs (A-D) and Sagittal11 sections of mandible, stained10 with H&E. mandibular foramen (E,F). Magnification,11 (A,C,E) x40; (B,D,F) x100. 1. mandibularTooth germ. foramen 2. Mental (E,F). nerve. 3. Incisive nerve.1. Tooth 4. Serre’s germ. 2.’ vein Mental in nerve.the separate 3. Incisive 294 4 osseousnerve. canal.4. Serre’s 5. Dental’ vein branches in the ofseparate theISSN Online 0719-2479 - www.joralres.com © 2017 4 inferiorosseous alveolar canal. nerve. 5. Dental 6. Inferior branches alveolar of the artery.7.inferior Inferior alveolar alveolar nerve. nerve. 6. Inferior 8. Lingual alveolar nerve.artery.7. 9. Mylohyoid Inferior alveolar nerve. 10. nerve. Mandibular 8. Lingual condylarnerve. 9.cartilage. Mylohyoid 11. nerve.Membranous 10. Mandibular part 8 6 of condylarmandible. cartilage. 11. Membranous part 8 6 Sagittalof mandible. sections of mandible, stained with H&E.Sagittal sections of mandible, stained with F Magnification, (A,C,E) x40; (B,D,F) x100. 7 9 H&E. F Magnification, (A,C,E) x40; (B,D,F) x100. 11 7 9 E F 11 E F Kabak SL, Zhuravleva NV & Melnichenko YM. Topography of the inferior alveolar nerve in human embryos and fetuses. An histomorphological study. J Oral Res 2017; 6(11):291-298. doi:10.17126/joralres.2017.082 to the side in the form of the mental nerve and divide that extends without a sharp boundary into connective into branches that are outside the lateral bone plate tissue around the other elements of the neurovascular (Figure 2B). bundle. The nerve consists of two main components In one of the embryos (34-mm CRL), the mental (primary bundles) (Figure 4A, B). Two bundles are in nerve division occurred before it passed through the contact with each other by the perineurium. In turn, described above gap. On the mesial side of the bone each of primary bundles splits into secondary bundles plate the incisive nerve can be observed. This nerve is separated by layers of connective tissue. The larger an extension of the inferior alveolar nerve in its course primary bundle is located on the buccal side and has a that can be traced to the midline of the lower alveolar multi-bundle structure. arch in the form of loosely arranged nerve fibers (Figure At the site of localization, it is identified as the mental 2C). Nerve fibers that originate from the incisive nerve nerve. The dental branch of the inferior alveolar nerve and follow to the anterior teeth are also revealed on this localized on the lingual side of the nerve, presents less stage of development (Figure 2D). bundle structure. In the fetuses of 13-16 weeks in utero, the inferior We observed one outstanding case. A few dental alveolar nerve becomes a compact nerve trunk, which branches were located at the level of the molar tooth splits at its mesial end into the mental and incisive nerve germ adjacent to the primary bundle of the inferior (Figure 3A). The nerve itself and its branches lie freely alveolar nerve. They were determined within the in the loose mesenchyme at a considerable distance composition of the neurovascular bundle located from the bone trabeculae. The mental nerve emerges between the two plates of the mandibular body within on the outer side of the lateral bone plate through a the general epineurium. Dental branches were presented wide mental foramen as one trunk or several branches. as separate bundles of nerve fibers surrounded by The incisive nerve is presented by one trunk consisting perineurium (Figure 4C, D). of several nerve bundles with dental branches to tooth In 20-week-old human fetuses, in the lower part germs. Nerve bundles lie parallel or form a plexus of the groove between the lateral and medial plates (Figures 3B and 3C). forming the mandibular body, a transversely oriented Dimensions of mandibular body increase in the bony trabecula was identified. Due to this trabecula, fetal period parallel to a partial involution of Meckel’s the intraosseous canal containing a wide thin-walled cartilage. The mandibular body consists of mesiodistally (venous) vessel is getting separated (Figure 4C). oriented trabeculae composing the woven bone. At In 20-week-old fetuses the mandibular foramen is the same time, the body of the mandible retains the not defined as a closed bone ring. The location of its appearance of a trough-like gutter containing a future position is approached in the contact area of the neurovascular bundle located at the bottom, and proximal end of condyle and the membranous part of tooth germs at the top. The canal of the mandible is the lower jaw. The inferior alveolar nerve, artery and not present as such because bone tissue surrounds the vein are positioned in that area at a great distance from inferior alveolar nerve, artery and vein on only three each other (Figures 4E and 4F). Above these structures, sides. The neurovascular bundle of a 20-week-old fetus separate from the neurovascular bundle, there is another molar is located closer to the alveolar ridge than to the large venous vessel. That represents a continuation of base of the mandible and the distance from the inferior the vein (Serre’s vein) located in a separate intraosseous alveolar nerve to the buccal surface is approximately canal at the bottom of the groove between the lateral twice as long as from the lingual surface of the body of and medial bone plates constituting the body of the the mandible. mandible. The inferior alveolar nerve’s branch, the At this stage of development, the main connective mylohyoid nerve, is located in the future mandibular tissue components of the inferior alveolar nerve are foramen region, slightly higher and laterally to the identified. On the surface, it is covered by epineurium nerve. The lingual nerve is detected on its medial side. ISSN Online 0719-2479 - www.joralres.com © 2017 295 Kabak SL, Zhuravleva NV & Melnichenko YM. Topography of the inferior alveolar nerve in human embryos and fetuses. An histomorphological study. J Oral Res 2017; 6(11):291-298. doi:10.17126/joralres.2017.082

DISCUSSION. Near the mental foramen the inferior alveolar nerve In human embryos in the early stages of prenatal separates into a larger part (the mental nerve) and a development, thick nerve trunks are present in smaller part that goes to the anterior teeth. Due to this undifferentiated mesenchymal mandibular processes. fact, the cross-sectional area of the nerve is becoming We have found that the anlage of Meckel’s cartilage, considerably reduced. Branching of the mental nerve which is a primary supporting structure of the can take place on the inner side with respect to the mandible and a crucial element in initiation of further lateral bone plate. Probably, in such cases an accessory development of the mandibular body, appears after mental foramen can subsequently be formed around the division of mandibular nerve into inferior alveolar one of the branches of the mental nerve. nerve and lingual nerve. Although the Meckel’s The type of the inferior alveolar nerve branching cartilage was previously supposed to serve as a template observed in fetuses in our study was described as the for bone deposition and to control endochondral and most frequent in cadaver studies in adults.3,13,14 The intramembranous bone formation during mammalian mental nerve occupies the buccal two-thirds of the mandibular development, the phenotypes of mutant inferior alveolar nerve, with the rest filled with the incisive mice do not directly support this hypothesis.9 nerve of the mandible.8 According to Hur et al.14 the During embryonic development, the number of lingual one-third of the inferior alveolar nerve contains branches of the inferior alveolar nerve increases, and its several fractions (bundles of nerve fibers). The superior fascicular structure changes. Beginning from the end buccal portion innervates molars; the superior portion, of the embryonic period of development, the inferior the premolars; and the upper and lower lingual portions alveolar nerve situated in a wide groove between two innervate canine and incisors. In our study, the lingual bone plates from the lateral side of the Meckel’s cartilage part of the inferior alveolar nerve of fetuses had several looks like a thick trunk without lateral branches. The bundles of nerve fibers, but it was not possible to trace mental nerve as its direct extension appears. At the their paths accurately. It can only be assumed that the beginning of the fetal period separate nerve fibers bundles lying somewhat apart are dental branches that heading into the tooth germs are revealed. extend from the trunk of the inferior alveolar nerve and In 20-week-old fetuses, at the level of the first molar then proceed to the tooth germs. the inferior alveolar nerve is somewhat closer to the Formally, the incisive nerve is one of the dental alveolar ridge than to the base of the mandible. In branches of the inferior alveolar nerve. It is detected contrast, in adults, when mandibular teeth are present, in human embryos even before the appearance of the the canal containing the inferior alveolar nerve is dental lamina, i.e. earlier than other dental branches. located closer to the base of the mandible than to the This gives grounds to consider it as an independent alveolar ridge.10 In the fetal period of development, the anatomical structure intended for innervation of the distance from the inferior alveolar nerve to the buccal anterior teeth. In adults the incisive nerve is in the same surface is approximately twice as long as from the canal in the anterior part of the body of the mandible. lingual surface of the body of the mandible. Adults have The incisive canal and nerve are not identified when a similar asymmetry in the location of the mandible the nerve passes through the gaps between bone canal containing the inferior alveolar nerve.11,12 trabeculae while running to the anterior teeth. The In 20-week-old human fetuses, the inferior alveolar nerve plexus providing an alternative to the incisive nerve usually appears as one compact trunk consisting nerve innervation of the canine and incisors, represents of two unequal parts. Each of these adjacent parts is individual anatomical variability and is formed at the surrounded by connective tissue. Some cross sections early stages of embryonic development, even before the have small bundles of nerve fibers (dental branches) formation of bone trabeculae in that area. lying at certain distance from the main nerve trunk. Chavez et al.15 described several individual foramina

296 ISSN Online 0719-2479 - www.joralres.com © 2017 Kabak SL, Zhuravleva NV & Melnichenko YM. Topography of the inferior alveolar nerve in human embryos and fetuses. An histomorphological study. J Oral Res 2017; 6(11):291-298. doi:10.17126/joralres.2017.082 on the lingual surface of the mandibular ramus in human Fetuses in the first half of pregnancy have the fetuses, which communicated with canals leading to inferior alveolar nerve located not in the canal, but in three groups of teeth: incisors, canines/premolars, and the groove, which is surrounded by bone on three sides. molars. It was assumed that those foramina and canals However, starting at the gestational age of 20 weeks, contain independent branches of the inferior alveolar a closed intraosseous canal containing a large venous nerve. The authors believed that in prenatal ontogenesis, vessel was detected in the mandibular body. This is the due to the rapid remodeling of the bone tissue, canals Serres canal with a vein of the same name, which is and foramina join together, and nerves merge. present in 60-73.7% of human fetuses, newborns and The assumption of the existence of three independent children under 13 years of age. The vein starts in the dental branches of the inferior alveolar nerve in human mental foramen area and it is not a tributary of the fetuses is widely used to explain the possible mechanism inferior alveolar vein. According to Rodríguez-Vásquez of the additional mandibular canal formation in adults. et al.16 the vein of Serres drains blood from the base of In our opinion, location of foramina and canals in mandible, while the inferior alveolar vein receives blood the body of the mandible is genetically predetermined from the alveolar part of the developing bone. and related to blood vessel and nerve branching in the mandibular processes at the early stages of prenatal CONCLUSION. ontogenesis. In our study we did not find three The architecture of intraosseous canals in the body independent branches passing to the teeth in embryos of the mandible, as well as the location of the foramina, and fetuses in the first half of pregnancy. is predetermined by the course and pattern of the Moreover, the general trend of the peripheral vessel/nerve branching in the mandibular arch, even nervous system genesis was shifting to the successive before the formation of bony trabeculae. Particularly, appearance of new smaller branches, rather than their the formation of the incisive canal of the mandible can fusion with each other. The formation of bone tissue be explained by the presence of the incisive nerve as the in the mandibular body occurs in the fetal period of extension of the inferior alveolar nerve. It has also been development of human embryos around already existing established that Meckel’s cartilage does not participate vascular and nerve structures. in mandibular canal morphogenesis.

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