This paper set out to document developmental changes of the fetal labyrinth during human fetal life. We found considerable size increases of the labyrinth during the early part of the period investigated, which gradually wane, and cease later in fetal life. Age-related shape changes of the labyrinth in superior view comprise an opening-out, or unfolding, about an origin in the region of the vestibule (Fig. 8). Antero-inferior parts (ASCi and COt) rotate clockwise, when considering the left labyrinth, and postero-inferior parts (LSCt, PSCm and PSCi) rotate anticlockwise. The more superior parts of the labyrinth (ASCm, ASCs and PSCs) remain stable. In lateral view, both the ampullar line segment and the cochlea axis rotate to a more upright orientation (clockwise for a left labyrinth; Fig. 8). These and other findings will now be discussed in more detail in relation to the four specific questions formulated in the Introduction.
The first question asked ‘at what age does the fetal labyrinth attain adult size’. Our findings show different rates of growth among the canals and cochlea, indicating that most components of the labyrinth, in particular the cochlea and lateral canal, follow distinct growth trajectories. It seems likely that the slower growth of the lateral canal corresponds to the proportional readjustments of its height in relation to its width. However, despite the growth lag of the lateral canal, we find that increases of all size measures, including overall size and that of the lateral canal, taper off to a plateau at around the same time, between 17 and 19 weeks gestation. Moreover, these plateaus of size are commensurate with the adult values reported by Spoor & Zonneveld (1998). Thus, our findings suggest that there is no evidence for growth of the labyrinth during the late fetal and postnatal period. These results confirm similar observations reported by Siebenmann (1890), Schönemann (1906) and Sato et al. (1991, 1993), but contradict previous suggestions that canal size and cochlea height increase postnatally (Hyrtl, 1845; Tremble, 1929; Turkewitsch, 1930). In fact, with respect to cochlear growth we find that it is this structure which perhaps first attains adult size at around 16–17 weeks gestation.
The second question asked whether labyrinthine morphology continues to change in shape after attaining adult size and after the otic capsule has ossified. The results indicate that the angle between the anterior and posterior canals continues to open laterally after the canals reach adult size, but stabilizes with the ossification of the surrounding capsule. Two angles, describing the torsion of the anterior canal (ASC-tor) and the orientation of the cochlea (COt<VSC), appear to change after ossification. However, the correlations with age are not strong, and after reaching adult size the cochlea angle is not different from that of adults. Moreover, the suggested direction of change for the small ASC-tor subset (Table 4) is opposite to that of the overall trend during the full fetal period investigated (Table 3). This would suggest a more complex pattern of shape changes, marked by reversals in direction. Figure 7(a), showing the full trend for the torsion angle, does not support such a pattern, and a larger post-ossification sample would need to be analysed to reject the null hypothesis of a single trend towards the adult morphology.
Sato (1903) reported that adult labyrinths show a 13° wider angle between the posterior limb of the lateral canal and the plane of the posterior canal than fetal labyrinths. Of all labyrinthine measurements used in our study, this phenomenon should best be expressed by the orientation of the axis of symmetry of the lateral canal (LSCt<VSC), but this angle is not correlated with age, and is not significantly different in the fetal and adult samples (Table 2). Moreover, relative to the midsagittal orientation the axis of symmetry does change over fetal time (Table 3), but in the opposite direction to that indicated by Sato, i.e. we find that LSCt turns more sagitally, with the vertex moving posteriorly rather than laterally.
Bossy & Gaillard de Collogny (1965) described that the long axis of the fetal labyrinth turns to a more coronal orientation by about 15°. Whereas the cochlea partly follows this rotation, the anterior canal rotates in the opposite direction by about 10°, and stabilizes at about 5 months. Although the age when shape changes cease approximately corresponds with our results, we do not find any age-related change of the equivalent measurement of the anterior canal (ASCm<SG). As Bossy & Gaillard de Collogny (1965) cover the time period from 2.5 to 9 months with a sample of just 12 fetuses, it may well be that the reported 10° change falls well within the normal interindividual variation, and does not represent a temporal trend (for a shorter period the variation in our sample is 29°).
Without specifically quantifying the difference, Sercer (1958) reports that adult semicircular canals show more torsion than those of newborns. Our study shows no evidence for increasing torsion after the fetal labyrinth attains adult size (Table 4). However, we did observe significant differences in comparisons with the adult means, suggesting that torsion of the anterior and posterior canals is greater in the adults. This could be seen as support for Sercer's general observation, except that we find the reverse pattern for the lateral canal, which shows more torsion in our fetal sample than in the adults (Table 2).
In addition to the torsion angles, two further angles of the labyrinth are significantly different in the adult sample and either the post-ossification fetal sample (Table 4) or the full fetal sample (Table 2). These are, respectively, the cochlear angle COs<LSCm, and the common crus angle CCR<LSCm, which is spatially linked with torsion of the vertical canals. Such differences probably reflect the distinct geographical compositions of the fetal and adult samples. The adults represent a worldwide sample, drawn from indigenous populations from all continents, whereas the fetal specimens represent the London (UK) area only. Given that Spoor (1993) observed population differences in adult labyrinthine morphology, this thus seems the most plausible explanation. However, it cannot be fully excluded that these morphological differences represent changes in labyrinthine shape after ossification of the otic capsule. This process would require local remodelling through resorption and deposition of bone, and this possibility should be examined through histological studies of the otic capsule. If it were to be demonstrated that angles with functional importance, canal torsion in particular, do change after capsule ossification, such an additional phase of plasticity could possibly be linked with fine-tuning of the vestibular apparatus.
Overall, our findings suggest that the fetal labyrinth shows little or no changes in shape after it has attained adult size and, in particular, once it is embedded in the ossified otic capsule.
The third question asked if the observed changes of the human fetal labyrinth are in any way interrelated with larger scale changes of the fetal cranial base. The partial correlation analyses did not reveal any link between shape changes of the labyrinth and the retroflexion of the midline cranial base. All parts of the labyrinth appear to follow the posterior cranial base, and not the anterior cranial base, so that the labyrinth pitches antero-inferiorly when the midline retroflexes. This appears to contrast with the observation of Spoor (1993) that the planar orientation of the lateral canal (LSCm) maintains a constant orientation relative to the anterior cranial base during human ontogeny. However, not only are these observations based on different measurements of the anterior cranial base (Spoor, 1993, considered the orientation sella to nasion, rather than to foramen caecum), they also cover dissimilar time periods. The eight fetal specimens considered by Spoor (1993) are between 24 weeks and full term. In the current study the eight equivalent specimens have an angle LSCm<S-Fc (mean = −5.5°, SD = 3.6°) that is very similar and not significantly different from the value for adults (Table 2). Hence, results indicate that the plane of the lateral canal pitches antero-inferiorly relative to the anterior cranial base up to about 24 weeks, and subsequently maintains a stable orientation into adulthood.
The partial correlation analyses do reveal an association between the increasingly coronal orientation of the petrous bones (PPip<SG) and changes to the cochlea. The basal turn of the latter both rotates coronally (COt<SG) and becomes more inclined (COs<LSCm), so that the cochlear apex faces more anteriorly. The coronal reorientation of the cochlea thus appears to follow the surrounding petrous bone, whereas other parts of the labyrinth do not. In the case of the vertical canal orientations, this may be because of inherent functional constraints, given that canal orientation directly affects its plane of optimum perceptive sensitivity. Functionally, all four vertical canals are integrated as contralateral synergistic push–pull pairs, and the adult configuration must be present when the planes become fixed by the end of the second trimester. However, this argument of functional constraint does not apply to the symmetry axis of the lateral canal (LSCt), because changes in its orientation do not affect the plane of the canal. Interestingly, LSCt rotates more sagitally with age (Fig. 8), as the petrous bone rotates coronally, but these movements are not correlated.
Whereas the joint coronal reorientation of the cochlea with the surrounding petrous bone is easily understandable, this is not the case for the increased cochlear inclination, measured in the sagittal plane. This correlation could be an indirect consequence of the spiral structure of the cochlea, so that any reorientation in the transverse plane (COt) affects the landmarks of the orientation in the sagittal plane (COs). The angles COt<SG and COs<LSCm are indeed significantly correlated (rproduct-moment−0.44**). However, when petrous orientation PPip is held constant the correlation is no longer significant (rpartial−0.16, ns), and the increased inclination of the cochlear basal turn is clearly not a simple consequence of its coronal reorientation.
Another unexpected finding is that, relative to the entire midline cranial base (S-Fc and Ba-S), the lateral canal (LSCm) pitches antero-inferiorly with coronal petrous reorientation. A specific explanation for this link is not evident, but it is interesting to note that it only applies to LSCm, and not to other labyrinthine orientations measured in the sagittal plane (Table 5). Among these, LSCm is also the only functionally relevant orientation, as it quantifies the plane of the lateral canal. A potential functional constraint on lateral canal orientation could be related to its input into the vestibulo-ocular reflex, working on the medial and lateral rectus muscles of the eye. Hence, a degree of alignment of these muscles, the bony orbit and the lateral canal planes is a possibility that remains to be explored (Spoor & Zonneveld, 1998). However, even if such a spatial association were found, it is not clear how this would relate to the orientation of the petrous bone.
Finally, the fact that only LSCm, and not COs, shows antero-inferior pitching in correlation with petrous reorientation may give new light to the poorly understood link between the cochlear inclination angle and petrous reorientation. Indeed, the correlation between the angles COs<LSCm and PPip<SG (Table 5) is no longer significant when the angles LSCm<Fs-S or LSCm<Ba-S are held constant (rpartial−0.17, ns, and −0.11 ns, respectively). This implies that the cochlear inclination angle is seen to co-vary with petrous reorientation not because of true inclination changes in COs but because of changes in the reference orientation LSCm.
In summary, the observed labyrintho–basicranial associations during fetal development reveal the following pattern: (1) a joint coronal reorientation of the petrous bone and the cochlea, not followed by other parts of the labyrinth; (2) the entire labyrinth follows the posterior cranial base, so that the former pitches antero-inferiorly, when the latter retroflexes; and (3) antero-inferior pitching of the lateral canal, relative to the anterior and posterior cranial base in association with coronal reorientation of the petrous bone.
Ontogenetic and phylogenetic trends
The fourth and final question asked if the human labyrinth is laid down as a small version of the phylogenetically derived adult morphology, and, if not, whether fetal changes reflect the phylogenetic trend observed for modern humans. The age-related shape changes observed here clearly demonstrate that the early fetal labyrinth does not show the adult morphology. Among these ontogenetic changes, some do indeed follow the phylogenetic trends observed when modern humans are compared with the extant great apes and Plio-Pleistocene hominids, the South African australopithecines in particular (Spoor, 1993; Spoor et al. 1994). Comparison of Figs 1 and 8 shows similar rotations of the ampullar line and the cochlea relative to the lateral canal (APA<LSCm, COs<LSCm). The ontogenetic and phylogenetic trends both also share a shape change of the posterior canal from a flat arc to one with negative torsion. However, the ontogenetic change appears to be caused by the increasingly sagittal orientation of the inferior part of the posterior canal, whereas the phylogenetic trend follows from an increasingly coronal orientation of its superior part (Spoor, 1993; Spoor & Zonneveld, 1998).
Several phylogenetic trends are not seen during fetal development. For example, the axis of symmetry of the lateral canal (LSCt) changes phylogenetically to a more coronal position (Fig. 1), but ontogenetically it remains unchanged (when measured against VSC) or even takes a more sagittal position (when measured against the midline SG). In addition, phylogenetically the common crus (CCR) rotates to a more posteriorly tilted orientation (Fig. 1), whereas no ontogenetic change was observed here.
The findings of the present study can now be used to evaluate the model that it is differential integration of the cartilagenous otic capsule and the surrounding fetal cranial base that results in the unique shape of the human labyrinth, as an ontogenetic process which could also form the basis of phylogenetic change (Spoor, 1993; Spoor & Zonneveld, 1998). The mechanism essential to this model is that parts of the labyrinth reorientate in correlation with the cranial base, whereas others remain stable or change independently. If the entire labyrinth simply follows the surrounding cranial base no shape change occurs, a situation shown by the antero-inferior pitch of the labyrinth in association with the retroflexion of the posterior midline cranial base. However, the mechanism is indeed demonstrated here by the exclusive reorientation of the cochlea and lateral canal plane in correlation with the petrous bones.
A second aspect of the model, that the differential link with the cranial base results in the derived, typically human shape of the labyrinth, is clearly not supported here. Most strikingly perhaps, the cochlea orientation COt follows the petrous bone ontogenetically, but shows no change phylogenetically, whereas the symmetry axis of the lateral canal LSCt reorientates with the petrous bone phylogenetically, but not ontogenetically (compare Figs 1b and 8b). The interpretation of the results with respect to the angles measured in the sagittal plane (Figs 1d and 8d) is more complex. Comparison could only be made with the midline cranial base, and not with the local inclination of the petrous surface, because the landmarks of the orientation PPp, used in adult comparisons, are not yet developed.
A third aspect of the model is the proposal that the process of fetal brain development affects both the pattern of change in the labyrinth and the pattern of basicranial variation, and that this common influence accounts for the link between the labyrinth and basicranium (Spoor, 1993; Spoor & Zonneveld, 1998). The potential impact of the brain on the cartilaginous otic capsules and the surrounding petrous bones is evident, as they are wedged between the cerebral temporal lobes and the cerebellum, and form a major line of attachment of the tentorium cerebelli. Moreover, phylogenetically, both midline cranial base flexion and coronal reorientation of the petrous bones have been shown to correlate with increased relative brain size (Ross & Ravosa, 1993; Ross & Henneberg, 1995; Spoor, 1997; Lieberman et al. 2000; McCarthy, 2001). However, analyses of the human fetal cranial base covering the same period as the present study indicate that these correlations do not occur ontogenetically (Jeffery & Spoor, 2002; Jeffery, 2003). Hence, whereas fetal brain growth may affect the labyrinthine shape locally, it is less likely to be the dominant factor integrating the labyrinth and the rest of the cranial base.
Overall, it can be concluded that there is evidence for the envisaged mechanism that the shape of the fetal labyrinth changes because parts follow the petrous bones but others do not. However, independent shape changes of the fetal labyrinth play at least as important a role in establishing the adult morphology. Moreover, ontogenetic patterns of shape change are not necessarily the basis for phylogenetic change of the labyrinth.
These and previous findings clearly highlight the complex nature of changes of the labyrinth and surrounding otic capsule during both development and evolution. A confounding factor is that studies thus far have only considered two-dimensional rotations of the labyrinth and the surrounding petrous bone, as a limited representation of complex three-dimensional changes. Although every attempt has been made here to cross-reference measures between the perpendicular transverse and sagittal planes, this is probably the reason for difficulties in understanding some results, such as the link between petrous reorientation in the transverse plane and rotation of the lateral canal in the sagittal plane. This study has been able to answer the basic questions regarding the ontogeny of the human labyrinth, but further advancing our understanding of its complexities will require full three-dimensional morphometric analysis.