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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 11
| Issue : 1 | Page : 17-22 |
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Development of the hair cells of the human cochlea: A scanning electron microscopic study
Sabita Mishra1, Tarasankar Roy2, Shubhi Saini1
1 Department of Anatomy, Maulana Azad Medical College, New Delhi, India
2 Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India
| Date of Submission | 22-Oct-2020 |
| Date of Decision | 26-Nov-2020 |
| Date of Acceptance | 01-Dec-2020 |
| Date of Web Publication | 16-Mar-2022 |
Correspondence Address:
Dr. Sabita Mishra
Director Professor, Maulana Azad Medical College, New Delhi
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/JMAU.JMAU_107_20
Introduction: In the mammalian auditory system, the cochlea is the first to attain structural and functional maturity. Although ultrastructural details of the developing cochlea of lower animals have been elucidated in the last few decades, comprehensive studies on human cochlea are lacking. Materials and Methods: In the present investigation we studied the development and maturation of the hair cells of ten human fetal cochlea from gestational weeks (GW) 12 to 37 by scanning electron microscopy. Result: We observed undifferentiated hair cells possessing numerous surface projections and long kinocilium during GW 14. At GW16, the primitive hair cells were arranged in one inner and four outer rows and had globular apices indicating the initiation of stereocilia formation. By GW 22, the globular apices were replaced by linear stereocilia and occasional kinocillia. Mature hair cells with sterocilia were observed in the basal turn at 30th week of gestation. At GW 37, the stereocilia were arranged in a typical “V” shaped pattern at the middle and apical coil, while the stereocilia of the basal turn were shorter in length resembling the adult cochlea. The inner hair cells were long and slender while outer hair cells were pear shaped, kinocilium were absent and the tunnel of Corti were well formed. Conclusion: It is concluded that in human, the morphological maturation of the hair cells starts in the basal turn around GW 22 and continues till 37th week in the apical turn indicating that early maturation of the cochlea may have a role on development of the higher auditory pathway connections.
Keywords: Development, internal ear, kinocilia, prenatal, sensory cells, stereocilia, ultrastructure
How to cite this article:
Mishra S, Roy T, Saini S. Development of the hair cells of the human cochlea: A scanning electron microscopic study. J Microsc Ultrastruct 2023;11:17-22 |
How to cite this URL:
Mishra S, Roy T, Saini S. Development of the hair cells of the human cochlea: A scanning electron microscopic study. J Microsc Ultrastruct [serial online] 2023 [cited 2023 Mar 31];11:17-22. Available from: https://www.jmau.org/text.asp?2023/11/1/17/339727 |
| Introduction | |  |
Congenital hearing loss results in cognitive deficits, communication difficulties, and delayed language development.[1] According to a WHO report (2011), there has been an appreciable increase in the incidence of congenital deafness worldwide.[2] In India, the incidence is 2–3 per 1000 live births and out of these children one is having profound degree of hearing loss.[3] Hearing in these children can be restored by cochlear implants.[4] Hence, it would be imperative to understand the development of the anatomical substrates of the auditory apparatus in human during prenatal period.
Sound waves are perceived by the hair cells of the organ of Corti in the cochlea. The human organ of Corti displays an intricate complex cellular organization. Among the cells of the organ of Corti, the epithelium consists of the inner and outer hair cells (IHC and OHC). The morphological maturation of cochlea can be studied by observing the developmental status of these two types of cells. It has been reported that the hair cell differentiation in human starts from rounded bodies at early ages.[5],[6] The OHC and IHC were observed as early as at 20 weeks of gestation week (GW)[7] and it was suggested that the cochlea responds to sound at high thresholds after 20 GW.[8] A kinocilium (a long slender cilia noted in immature hair cells) like structure has been identified on the surface of sensory cells.[9],[10],[11] Morphologic studies of the cochlea in lower animals revealed that it is possible to distinguish the functional from the nonfunctional organ of Corti by observing the formation of the tunnel of Corti, opening of space of Nuel, and disappearance of kinocilium.[10],[11],[12]
The structure and function of the cochlea has been correlated with lower animals and it was observed that complete maturation of the cochlea follows initiation of function. In human, the cochlear functions are elicited by GW 18–20 and mature cochlea is probably seen at 2 months after birth.[8] The sensory hair cells, of the organ of Corti generates periodic action potential as early as GW 16, which stimulate the spiral ganglion neurons before the onset of hearing.[13],[14] This spontaneous activity drives the maturation of other circuits in the auditory pathway. Physiological responses to auditory stimuli are also demonstrable after 20 GW when the cochlear nerve shows initiation of myelination.[15] This signifies that developing cochlea influence the further maturation of the higher auditory pathway and some part of the cochlea is morphologically mature and ready for reception of sounds.[16]
There are large number studies available on the development and maturation of the cochlea and hair cells in lower mammals but limited data are available in the human.[7],[17],[18],[19],[20],[21],[22]
In the present study, we have evaluated the morphological maturation of the human fetal cochlea to understand the subtle differences between the functional and nonfunctional cochlea during the mid and late prenatal period. We also studied the surface morphology and ciliogenesis in the hair cells of human cochlea at various gestational periods. Data from this study will help in understanding the mechanism of onset of hearing in human and other mammals.
| Materials and Methods | | |
Collection of fetus
Ten fetuses aged between 12 and 37 GW were collected from the labor rooms and mortuary of the All India Institute of medical Sciences (AIIMS) New Delhi after obtaining institutional ethical committee clearance and taking informed consent from the parents [Table 1]. The fetuses aged below 20 WG were collected from cases where medical termination of pregnancy (MTP) was performed for family planning (legalized in India under MTP-Act, Government of India, 1971), while those older than 20 WG were still-births and intrauterine deaths (IUDs). The later gestational age fetuses (after 22 weeks) were obtained from spontaneous abortion cases, still birth and IUDs cases and the 37-week fetus was a stillborn, received immediately after expulsion. The maternal health status was assessed, and the fetuses were checked for any gross abnormality immediately after abortion/expulsion. Fetuses showing no gross abnormality were accepted for the study. Crown-rump length, bi-parietal diameter, foot length, and weight of the fetus were measured to determine the age and were categorized into different groups.[23],[24] After dissection, the brain was removed from the cranium and the head was preserved in 4% paraformaldehyde solution at 4°C. | Table 1: Number of fetus collected with their gestational age (in weeks)
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Dissection of cochlea
To study the cochlea, the petrous part of the temporal bone along with the ear were detached from the skull and kept in the fixative for 48 h. Under the dissection microscope, the perilymphatic space was identified and a 4% paraformaldehyde solution was injected into the petrous part of the temporal bone.[25] Temporal bone from late gestational age fetuses (beyond 20 weeks) was decalcified in 10% ethylenediaminetetracetic acid. Removal of the bone from the roof and lateral wall of the petrous part exposed the bony cochlea, which was dissected under a Zeiss dissection microscope to visualize the membranous cochlea. The roof of the membranous cochlea was incised using a sharp scalpel blade. The vestibular membrane was stripped out from the osseous spiral lamina by a fine needle. The tectorial membrane was washed off and detached from the hair cells with a jet of water injected from a tuberculin syringe.
Scanning electron microscopy
The dissected cochlea was processed for scanning electron microscopy using the standard protocol.[26] The tissue was dehydrated and kept for critical point drying, following which it was mounted on a stub, coated with gold, observed and photographed under a LEO 435 scanning electron microscope (SEM).
| Results | | |
The cochlea of the 12 weeks' fetus was mesenchymatous and had acquired the spiraling of two and half turns. However, we were not able to observe the hair cells.
The mesenchymatous cochlea was almost converting into a cartilaginous cochlea at 14 GW. From 16–20 GW the cochlea became cartilaginous. Later, the cochlea gradually got ossified and became completely bony by 37 GW.
At 14th GW, the cartilaginous cochlea had two and half turns while the otic capsule was translucent [Figure 1]a. Under the SEM, the tectorial membrane appeared adherent to the surface epithelium which was not fully developed. The surface of the developing organ of Corti had number of cells with numerous villous projections, while the hair cells had a distinct long kinocilium around which the few cilia were observed. It was not possible to differentiate the inner and outer hair cells. There were some smaller cells (primitive supporting cells) in between the developing sensory cells [Figure 1]b. | Figure 1: (a) Two and half turns of the cochlea at 14 weeks of gestation (arrow). The cochlea is thin translucent and cartilaginous at this age. The internal acoustic meatus is also visible (arrow head). Scale bar = 125 μm. (b) Scanning electron micrograph of the surface epithelium of the developing organ of Corti at 14 weeks of gestation. The undifferentiated hair cells show a long kinocilium (K), surrounding it is the developing stereocilia (arrow). Scale bar = 20 μm
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At GW 16–18, the developing cochlea had its usual shape of two and half turns. The tectorial membrane could be easily stripped off from the hair cells. Majority of the hair cells had globular tops where the primitive stereocilia were seen to project out from its periphery [Figure 2]a. In some places, the globular apices disintegrated to form the cilia [Figure 2]b. There was a single layer of inner hair cells and 4 layers of outer hair cells. The stereocilia of hair cells had no regular pattern of arrangement. They were of unequal height and arranged in clumps [Figure 2]b. While some of the stereocilia were appearing from the peripheral part of the globules, few were emerging from the central core of the globular structure. The middle two rows of OHC showed less ciliogenesis in comparison to other rows and the cilia did not show any regular pattern of arrangement. A thin and slender kinocilium was noted among the bundle of irregular stereocilia however, at some places rudimentary kinocilium was also noted. The rest of the surface of the hair cells were covered with microvilli [Figure 2]c. | Figure 2: (a) Scanning electron micrograph of the human organ of Corti at 16 weeks of gestation showing four rows of outer hair cells (O) and a single row of inner hair cells (I). The apices of the hair cells are globular. Inner hair cells look less mature in comparison to outer hair cells. Few stereocilia seen to grow from the periphery of the hair cells (arrow). Scale bar = 10 μm. (b) Scanning electron micrograph of the human organ of Corti at 16 weeks of gestation. Note the bundle of stereocilia emerging from the periphery of the globular structures (arrow). Some of the apices present smooth globular structures, while some are rough and appear to be disintegrating to give rise to the stereocilia bundle. Scale bar = 100 μm. (c) Scanning electron micrograph of the human organ of Corti at 16 weeks of gestation. The hair cells are long and slender and are covered with microvilli. Bundle of stereocilia can be seen to emerge from the apical part and are rupturing a thin membrane (arrow head). Note the bundle of stereocilia having a single thin kinocilium (K) in one bundle. Scale bar = 10 μm
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At 22 GW, a single row of inner hair cells and four rows of outer hair cells were noted. Most of the hair cells in the outer row were well developed, although few cells in the middle row showed globular apices and the apical portion of these cells had stereocilia. The hair cells were of equal height and had a linear arrangement; at some places a “V-” shaped arrangement was observed. An occasional long and slender kinocilium was noted in some of the sterocilia bundles. The cell surface was covered by coarse microvilli. The stereocilia on the inner hair cell was longer and thicker in comparison to the outer hair cells. The tunnel of Corti and space of Nuel were well formed [Figure 3]. | Figure 3: Scanning electron micrograph of the organ of Corti at 22 weeks of gestation showing the stereocilia of the inner hair cells (I) arranged in a single row and 4 rows of outer hair cells (O) arranged in a wide V shaped pattern. The tunnel of Corti (arrow) is formed and hair cells are covered by microvilli. The stereocilia of the inner hair cells appear to be longer and thicker than the outer hair cell. Occasional kinocilium (K) are visible in the bundle of stereocilia. Scale bar = 1 μm
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At 30 GW, the cochlea attained adult shape of two and a half turns and the cartilaginous cochlea was completely ossified which was removed to expose the membranous cochlea. The membranous labyrinth of the cochlea also followed the same two and half turn pattern [Figure 4]a. The membranous cochlea was incised from the roof to expose the organ of Corti [Figure 4]b. The hair cells were well differentiated and the tectorial membrane was well developed. Elongated outer hair cells were seen and inner hair cells had relatively rounded appearance. The cilia were of equal length, and aligned in a straight line. No kinocilium was observed. | Figure 4: (a) The bony cochlea at 30 weeks of gestation has been dissected to expose the membranous cochlea. Two and half turns (adult form) of the cochlea can be seen by this age. Corti. Scale bar = 250 μm. (b) Scanning electron micrograph of the human cochlea at 30 weeks of gestation. Scale bar = 300 μm
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The cochlea had complete two and half turns and was totally bony by 37th GW similar to the 30th GW cochlea [Figure 5]a. The membranous cochlea was of two and half turns, which were incised to expose the hair cells [Figure 5]b. A single row of mature inner hair cells and four rows of mature outer hair cell were observed. The tunnel of Corti was well defined [Figure 5]c. In the outer hair cells, the stereocilia were arranged in four rows and had a “V” shaped arrangement [Figure 5]d. The cell surfaces were covered by fine microvilli, towards the lateral side of the cell bodies of the outer hair cells where nerve fibers were seen emerging [Figure 5]d. In the inner hair cell, the stereocilia were of equal height and had almost a linear arrangement, whereas in the OHC the stereocilia were arranged parallel to each other. The sterocilia on the IHC were short, thicker clumped together and were uniform throughout the cochlea. The OHC were almost twice the length of the inner hair cells and the length of the stereocilia was almost equal to the height of the cell body [Figure 5]e. The inner hair cells showed a globular shape, while the outer hair cells were long and slender [Figure 5]d. The supporting cells were also well developed. The tunnel of Corti and space of Nuel were prominent [Figure 5]c. At a higher magnification, the stereocilia were observed to be in clumps with tip links connecting them, they were almost of equal height, and had staircase like arrangement. Kinocilia were not observed among the bundle of stereocilia. Cell surface was covered all over by fine microvilli [Figure 5]f. The hair cells of the basal turn showed shorter cilia in comparison to those on the middle and apical coils [Figure 5]g. | Figure 5: (a) Scanning electron micrograph of the human organ of Corti at 37 weeks of gestation. The boxed area shows the organ of Corti in the middle coil. Scale bar = 10 μm. (b) Scanning electron micrograph of the human organ of Corti, middle turn, at 37 weeks of gestation showing four rows of outer hair cells (O) and a single row of inner hair cells (I), and supporting cells (S). Scale bar = 10 μm. (c) Scanning electron micrograph of the organ of human Corti, middle turn, at 37 weeks of gestation showing four rows of outer hair cells (O) and one row of inner hair cells (I) and also the supporting cells (S). Curved arrow points at the tunnel of Corti. Scale bar = 20 μm. (d) Scanning electron micrograph of the organ of human Corti, middle turn, at 37 weeks of gestation showing that stereocilia of the outer hair cells (O) are arranged in a V shaped pattern. The cells are long and slender (arrow). Scale bar = 10 μm. (e) Scanning electron micrograph of the human organ of Corti at 37 weeks of gestation showing 4 rows of outer hair cells (O) which appear to be longer while a single layer of inner hair cells are shorter (I). The stereocilia of the inner hair cells are clumped and longer in comparison to the stereocilia of the outer hair cells. Scale bar = 10 μm. (f) Scanning electron micrograph of the human organ of Corti, middle turn, at 37 weeks of gestation showing a bundle of stereocilia which are clumped together. Scale bar = 20 μm. (g) Scanning electron micrograph of the basal turn of the organ of Corti, at 37 weeks of gestation showing 4 rows of outer hair cells. The length of stereocilia is shorter in comparison to the middle turn. The arrangement of stereocilia is almost linear. Scale bar = 5 μm
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| Discussion | | |
We have previously described the development and maturation of the auditory pathway which describes the developing cochlear nerve,[15] the cochlear nucleus[27],[28] and inferior colliculus.[29] In the present study, we have examined the prenatal morphological development of the human cochlea chronologically from GW 12–37 using scanning electron microscopy. Here, we have tried to focus more on the development of sensory hair cells which has a significance in the functional maturation of auditory system.
In our study, we observed that at GW 12 the cochlea was thin, translucent cartilaginous (the earliest age we studied), and acquired the regular two and half turns. Previous studies have described that the curved tube derived from cochlear duct forms two-three fourth turns around 7–11 GW.[30] Several reports suggest that the human cochlea acquire its shape of two and half turn by the GW 9.[31] In the present study, the earliest fetus dissected was 12 weeks of age, hence we were not able to comment on the time frame when the cochlea acquired the two and half turn shape. In our study, ossification of the otic capsule was observed between GW 16 to GW 30 and complete ossification was observed by GW 37, which is contrary to previous studies which have reported that the ossification and mineralization of cochlea occurred between GW17–39.[32]
At GW 14, numerous villous projections were seen on the surface epithelium of the cells of the human organ of Corti. The developing sensory cells could be distinguished from the rest of the surface cells by the presence of a long kinocilium which is similar to the picture described in different mammalian cochlea.[33],[34],[35],[36] The kinocillium, is responsible for the alignment of the bundle of stereocillia which emerges from the apices of the hair cells and regresses once functional hearing starts.[6],[37] We observed the developing sensory epithelium at GW 14, although hair cell differentiation has been described as early in human at GW 12.[6] A recent study[38] has also shown the differentiation of hair cell and formation of organ of Corti at 14 GW similar to our study. The present study showed appearance of the hair cells at 14 weeks but the differentiation into IHC and OHC was not observed. The difference in the hair cell differentiation in comparison to animal studies may be due to the fact that human tissue is obtained from abortuses, which may not show excellent morphology due to poor or late fixation. However, distinguishable IHCs and OHCs has been detected in mice and rats at E17[39] which corresponds to 14 WG in human.[14] In the current study at GW 16 sensory cells were aligned in a single row of inner hair cells and four rows of outer hair cells which had globular apices similar to the round body (tuffs) described previously.[40] The globular apices gave an appearance of a mushroom, which were first smooth, later became rough and finally disintegrated to form the stereocilia from the periphery. These globular and bulbous cytoplasmic processes were also reported in new born kitten.[41] However, transmission electron microscopy observations in human fetus[42] reveals that these globular structures are projections from the cuticular plate of the hair cells with direct continuation of the plasma membrane and that auditory stereocilia are differentiated from them. We observed initiation of stereociliogenesis at 16 GW, first in the IHC and later in the OHC which is similar to a previous description.[6],[8] The stereocilia were arranged around the kinocilium and the length and thickness of the single kinocilium within a bundle of stereocilia decreased. In human, there was no regular pattern of arrangement of the hair cells as described in other experimental animals such as cats, rats, mice, guinea pigs, and hamster.[33],[40],[43]
By 22 weeks, the globular apices were replaced by stereocilia that were aligned as single inner row and four rows of outer cells and occasional kinocilium were seen. The stereocilia on inner hair cells were thicker and longer as compared to the outer hair cells, similar to other mammalian cochlea.[44] However, the tunnel of Corti started appearing at 16 GW, and a definite tunnel of Corti and space of Nuel was observed from 22 GW. This shows that the cochlea is functionally mature by this stage. Maturational changes such as formation of tunnel of Corti, space of Nuel and changes in the shape of hair cells were also seen in rats at PND 12 (Roth et al., 1992).
At 37 weeks, well-defined mature hair cells with stereocilia were observed; single row of OHC gave an appearance of a “V-” shaped pattern while the stereocilia on a single hair cell was arranged in a linear fashion. Microvilli and supernumerary stereocilia disappeared from the developing cuticular plate. The OHC were arranged in three to four parallel rows where the sterocilia were in a staircase pattern according to its height. We also observed lateral and tip links during maturation as described earlier [Figure 5]d.[6],[37] Furthermore, at this time point, there was no kinocilium on the bundle of stereocilia. In case of IHC, a linear arrangement of stereocilia was observed. The length of the stereocilia changed during maturation and the final length of the stereocilia depended on the height of the hair cell. Similar morphology was also noted in mice.[45] At the onset of cochlear function, the kinocilium regress and disappear, first on the OHC then on the IHC as previously reported.[46]
In mammals, the cochlear function begins even before the complete morphological maturation.[8] With increasing age a gradual increase in size of the cochlea and thickness and length of the stereocilia were observed in the present study. These findings are in agreement with those reported for experimental mammals and birds.[6],[10],[37],[40] In the human fetus, maturation of the OHC occurred before the IHC.[47] This has also been reported in hamsters, though the inner hair cells are the first to appear. The stereocilia increased in length and thickness with increasing gestational ages, however, we have described a sequential pattern of stereociliogenesis which was not described previously.[40] We observed that IHC has the same length throughout the cochlea, while the adult OHC increases gradually in length from the base to apex as previously reported.[45]
The present study is one of the first detailed reports on the surface morphology of the developing human cochlea, where the maturity of hair cells has been described sequentially at different gestational ages.
| Conclusion | | |
In summary, we studied the development, differentiation and maturation of the hair cells in the human cochlea by scanning electron microscopy, at different gestational ages ranging from GW 12–37. We observed that the hair cells develop from primitive round bodies, which appear during GW 16. During GW 18 to GW 22, these bodies disintegrate to form bundle of stereocilia with a single kinocilium. The kinocilium start disappearing during GW 22. By GW 30, the majority of hair cells in the basal turn are mature, whereas the majority of cells are adult like during GW 37.
Thus, the organ of Corti in the human cochlea attains morphological maturation before birth, suggesting that early maturation of the cochlea may have a role on development of the higher centers of the auditory pathway.
Acknowledgment
We acknowledge the contribution of Prof. Shashi Wadhwa, former head of department of Anatomy and faculty incharge of electron microscopy, AIIMS, New Delhi. We would also like to thank the faculty of Department of Obstretics and Gynaecology for providing the samples. This research was supported by All India Institute of Medical Science, New Delhi.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1]
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