Early history of subplate and interstitial neurons: from Theodor Meynert (1867) to the discovery of the subplate zone (1974)

In this historical review, we trace the early history of research on the fetal subplate zone, subplate neurons and interstitial neurons in the white matter of the adult nervous system. We arrive at several general conclusions. First, a century of research clearly testifies that interstitial neurons, subplate neurons and the subplate zone were first observed and variously described in the human brain - or, in more general terms, in large brains of gyrencephalic mammals, characterized by an abundant white matter and slow and protracted prenatal and postnatal development. Secondly, the subplate zone cannot be meaningfully defined using a single criterion - be it a specific population of cells, fibres or a specific molecular or genetic marker. The subplate zone is a highly dynamic architectonic compartment and its size and cellular composition do not remain constant during development. Thirdly, it is important to make a clear distinction between the subplate zone and the subplate (and interstitial) neurons. The transient existence of the subplate zone (as a specific architectonic compartment of the fetal telencephalic wall) should not be equated with the putative transient existence of subplate neurons. It is clear that in rodents, and to an even greater extent in humans and monkeys, a significant number of subplate cells survive and remain functional throughout life.     

The total number of white matter interstitial neurons in the human brain

In the adult human brain, the interstitial neurons (WMIN) of the subcortical white matter are the surviving remnants of the fetal subplate zone. It has been suggested that they perform certain important functions and may be involved in the pathogenesis of several neurological and psychiatric disorders. However, many important features of this class of human cortical neurons remain insufficiently explored. In this study, we analyzed the total number, and regional and topological distribution of WMIN in the adult human subcortical white matter, using a combined immunocytochemical (NeuN) and stereological approaches. We found that the average number of WMIN in 1 mm³ of the subcortical white matter is 1.230 ± 549, which translates to the average total number of 593 811 183.6 ± 264 849 443.35 of WMIN in the entire subcortical telencephalic white matter. While there were no significant differences in their regional distribution, the lowest number of WMIN has been consistently observed in the limbic cortex, and the highest number in the frontal cortex. With respect to their topological distribution, the WMIN were consistently more numerous within gyral crowns, less numerous along gyral walls and least numerous at the bottom of cortical sulci (where they occupy a narrow and compact zone below the cortical‐white matter border). The topological location of WMIN is also significantly correlated with their morphology: pyramidal and multipolar forms are the most numerous within gyral crowns, whereas bipolar forms predominate at the bottom of cortical sulci. Our results indicate that WMIN represent substantial neuronal population in the adult human cerebral cortex (e.g. more numerous than thalamic or basal ganglia neurons) and thus deserve more detailed morphological and functional investigations in the future.     

Sublaminar organization of the human subplate: developmental changes in the distribution of neurons,glia, growing axons and extracellular matrix

The objective of this paper was to collect normative data essential for analyzing the subplate (SP) role in pathogenesis of developmental disorders, characterized by abnormal circuitry, such as hypoxic‐ischemic lesions, autism and schizophrenia. The main cytological features of the SP, such as low cell density, early differentiation of neurons and glia, plexiform arrangement of axons and dendrites, presence of synapses and a large amount of extracellular matrix (ECM) distinguish this compartment from the cell‐dense cortical plate (CP; towards pia) and large fiber bundles of external axonal strata of fetal white matter (towards ventricle). For SP delineation from these adjacent layers based on combined cytological criteria, we analyzed the sublaminar distribution of different microstructural elements and the associated maturational gradients throughout development, using immunocytochemical and histological techniques on postmortem brain material (Zagreb Neuroembryological Collection). The analysis revealed that the SP compartment of the lateral neocortex shows changes in laminar organization throughout fetal development: the monolayer in the early fetal period (presubplate) undergoes dramatic bilaminar transformation between 13 and 15 postconceptional weeks (PCW), followed by subtle sublamination in three ‘floors’ (deep, intermediate, superficial) of midgestation (15–21 PCW). During the stationary phase (22–28 PCW), SP persists as a trilaminar compartment, gradually losing its sublaminar organization towards the end of gestation and remains as a single layer of SP remnant in the newborn brain. Based on these sublaminar transformations, we have documented developmental changes in the distribution, maturational gradients and expression of molecular markers in SP synapses, transitional forms of astroglia, neurons and ECM, which occur concomitantly with the ingrowth of thalamo‐cortical, basal forebrain and cortico‐cortical axons in a deep to superficial fashion. The deep SP is the zone of ingrowing axons – ‘entrance (ingrowth) zone’. The process of axonal ingrowth begins with thalamo‐cortical fibers and basal forebrain afferents, indicating an oblique geometry. During the later fetal period, deep SP receives long cortico‐cortical axons exhibiting a tangential geometry. Intermediate SP (‘proper’) is the navigation and ‘nexus’ sublamina consisting of a plexiform arrangement of cellular elements providing guidance and substrate for axonal growth, and also containing transient connectivity of dendrites and axons in a tangential plane without radial boundaries immersed in an ECM‐rich continuum. Superficial SP is the axonal accumulation (‘waiting compartment’) and target selection zone, indicating a dense distribution of synaptic markers, accumulation of thalamo‐cortical axons (around 20 PCW), overlapping with dendrites from layer VI neurons. In the late preterm brain period, superficial SP contains a chondroitin sulfate non‐immunoreactive band. The developmental dynamics for the distribution of neuronal, glial and ECM markers comply with sequential ingrowth of afferents in three levels of SP: ECM and synaptic markers shift from deep to superficial SP, with transient forms of glia following this arrangement, and calretinin neurons are concentrated in the SP during the formation phase. These results indicate developmental and morphogenetic roles in the SP cellular (transient glia, neurons and synapses) and ECM framework, enabling the spatial accommodation, navigation and establishment of numerous connections of cortical pathways in the expanded human brain. The original findings of early developmental dynamics of transitional subtypes of astroglia, calretinin neurons, ECM and synaptic markers presented in the SP are interesting in the light of recent concepts concerning its functional and morphogenetic role and an increasing interest in SP as a prospective substrate of abnormalities in cortical circuitry, leading to a cognitive deficit in different neurodevelopmental disorders.     

Development of fetal hypothalamic magnocellular neurosecretory neurons transplanted into the third ventricle of the adult rat brain

Department of Biology, N. I. Pirogov Second Moscow Medical Institute. Department of Biology, Khar'kov Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Smirnov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 105, No. 2, pp. 224–227, February, 1988.     

Infection of human fetal dorsal root neurons with wild type varicella virus and the Oka strain varicella vaccine

The relative ability of a varicella-zoster virus (VZV) clinical isolate and a live attenuated VZV vaccine strain (Oka) to infect human neurons was determined in vitro. VZV infection of neurons prepared in culture from dorsal root ganglia of fetuses was assessed using an infectious center assay. Cultures were infected with 50–5,000 pfu of either VZV and assayed at either 24 or 48 hours post-VZV infection. Cultures infected with the clinical VZV isolate had seven-fold more infected neurons than cultures infected with the vaccine strain VZV. © 1993 Wiley-Liss, Inc.     

Cytology and time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon

Summary The fine structure, synaptic relationships, distribution and time of origin of interstitial neurons situated within the white matter subjacent to the visual, somatosensory and motor cortices were studied in the human and monkey telencephalon. The analysis was carried out on Nissl-stained serial sections, rapid Golgi impregnations, by acetylcholinesterase (AChE) histochemistry, electron microscopy and [³H]thymidine ([³H]TdR) autoradiography. Interstitial neurons have a similar distribution, morphology and histochemistry in both human and monkey telencephalon. Their highest density and the most extensive distribution is found in the neonatal period in both species. The number of interstitial neurons decreases during infancy, but numerous cells remain in the adult.Two types of interstitial neuron can be recognized in Golgi preparations:polymorphic cells, usually situated close to the cortex andfusiform cells, located predominantly in the depths of the white matter. The polymorphic cell type is prevalent during neonatal and infant stages, while fusiform cells are relatively more numerous in the adult. Interstitial cells have ultrastructural features and organelles typical of neurons of the central nervous system with well-defined axosomatic and axodendritic synapses of both symmetrical and asymmetrical types. About 20% of the interstitial cells show strong specific AChE activity.Autoradiographic analysis of postnatal monkeys exposed to [³H]TdR at various embryonic (E) and early postnatal days indicates that interstitial neurons which lie beneath the visual and somatosensory-motor cortices are generated between E38 and E48. Contrary to the prevailing notion that interstitial neurons are the latest generated cells arrested during migration across the maturing white matter, they prove to be produced at the end of the first third of the 165-day gestation in the rhesus monkey concomitantly with the generation of neurons destined for the deep neocortical layers. These findings raise the possibility that interstitial cells represent a vestige of the transient embryonic subplate layer.     

Effects of lesion of the interstitial nucleus of Cajal on vestibular horizontal canal neurons in the cat

Effects of procaine infusion into the interstitial nucleus of Cajal (INC) on vestibular nuclear neurons related to the horizontal canal were studied in cats anesthetized with nitrous oxide and paralyzed with gallamine. Neurons that responded to sinusoidal horizontal rotation (at 0.18 Hz) were recorded extracellularly in the medial and descending vestibular nuclei. Spontaneous activity of type I neurons increased, whereas that of type II neurons decreased following procaine infusion into the ipsilateral INC. Gain of the neuronal response to horizontal rotation decreased after the ipsilateral INC infusion, but there was no consistent effect on phase. Infusion into the contralateral INC seemed less effective. Similar effects were obtained with electrolytic lesions that were confined to the ipsilateral INC area. These results suggest that the INC influences type I neurons through inhibitory action of type II neurons and that it eventually controls the gain, but not the phase, of the horizontal vestibular reflexes.     

Development of axonal pathways in the human fetal fronto-limbic brain: histochemical characterization and diffusion tensor imaging

The development of cortical axonal pathways in the human brain begins during the transition between the embryonic and fetal period, happens in a series of sequential events, and leads to the establishment of major long trajectories by the neonatal period. We have correlated histochemical markers (acetylcholinesterase (AChE) histochemistry, antibody against synaptic protein SNAP‐25 (SNAP‐25‐immunoreactivity) and neurofilament 200) with the diffusion tensor imaging (DTI) database in order to make a reconstruction of the origin, growth pattern and termination of the pathways in the period between 8 and 34 postconceptual weeks (PCW). Histological sections revealed that the initial outgrowth and formation of joined trajectories of subcortico‐frontal pathways (external capsule, cerebral stalk–internal capsule) and limbic bundles (fornix, stria terminalis, amygdaloid radiation) occur by 10 PCW. As early as 11 PCW, major afferent fibers invade the corticostriatal junction. At 13–14 PCW, axonal pathways from the thalamus and basal forebrain approach the deep moiety of the cortical plate, causing the first lamination. The period between 15 and 18 PCW is dominated by elaboration of the periventricular crossroads, sagittal strata and spread of fibers in the subplate and marginal zone. Tracing of fibers in the subplate with DTI is unsuccessful due to the isotropy of this zone. Penetration of the cortical plate occurs after 24–26 PCW. In conclusion, frontal axonal pathways form the periventricular crossroads, sagittal strata and ‘waiting’ compartments during the path‐finding and penetration of the cortical plate. Histochemistry is advantageous in the demonstration of a growth pattern, whereas DTI is unique for demonstrating axonal trajectories. The complexity of fibers is the biological substrate of selective vulnerability of the fetal white matter.     

Parasympathetic neurons of salivary gland ganglia in the fetal and postnatal rat are substance P-like immunoreactive

Substance P-like immunoreactivity (SPLI) of neuron cell bodies is described here in the parasympathetic ganglia of salivary glands in rat fetuses. When grafted to the anterior eye chamber of adult rats, outgrowth of SPLI fibers was also observed around fetal and postnatal ganglia. These observations are significant for the understanding of salivation mechanisms. They also imply the importance of substance P or related compounds in parasympathetic peripheral neurons. The graft experiments indicate a substantial morphological plasticity of these SPLI neurons on perturbation.     

Fetal lung interstitial tumor: The first Japanese case report and a comparison with fetal lung tissue and congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3

Fetal lung interstitial tumor, a newly recognized lung lesion in infants, was first reported in 2010. Here, we report the first Japanese case of fetal lung interstitial tumor which was originally diagnosed as atypical congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3. A 7‐day‐old girl was referred to our hospital with respiratory distress and a left lung mass and she subsequently underwent left lower lobectomy. The specimen showed a 5 cm solid mass with a fibrous capsule. Histological examination revealed immature airspaces and interstitium, containing bronchioles and cartilage. The epithelial and interstitial cells contained abundant glycogen granules. Immunohistochemistry showed nuclear/cytoplasmic expression of β‐catenin in the epithelial and interstitial cells. β‐catenin gene mutations and trisomy 8 were not detected, so a neoplastic origin could not be confirmed. The histological findings were partly consistent with normal fetal lung at the canalicular stage, pulmonary interstitial glycogenosis, and congenital cystic adenomatoid malformation/congenital pulmonary airway malformation type 3. In this report, we compare the above conditions and discuss the pathogenesis of fetal lung interstitial tumor.     

Organisation of basement membrane components in the human adult and fetal pituitary gland and in pituitary adenomas

 Cell–matrix interactions undoubtedly have a role in the development and maintenance of the complex nonrandom structure of the human pituitary gland. We have extended previous studies by documenting the patterns of immunoreactivity for type IV collagen, laminin and fibronectin in the fetal gland, comparing these with the adult patterns. In both we have examined the differences between the anterior lobe and intermediate zone in an attempt to elucidate the apparent differences in functional response between corticotrophs in the two areas. We have also examined expression of these proteins in a series of pituitary adenomas. Finally, we have immunolocalised β₄ integrin, a component of the α₆β₄ laminin receptor, in the adult gland and in adenomas. In the anterior lobe of the adult gland, type IV collagen and laminin were present in both epithelial and vascular basement membrane. Fibronectin was related to the basement membrane but showed a less continuous distribution. β₄ Integrin was expressed on the basal aspects of pituitary cells, in association with laminin, suggesting that this did identify the α₆β₄ laminin receptor. In addition, immunoreactivity was present on the lateral margins of some pituitary cells, which might indicate a role in cell–cell adhesion. None of the proteins showed specific association with any particular cell type, suggesting that these specific interactions do not regulate differentiation. This pattern of expression had developed in the fetal gland by the second trimester, with expression relating to vessels preceding that in epithelial basement membrane. Type IV collagen, laminin and fibronectin were also expressed in epithelial and vascular basement membrane in the intermediate zone of the adult gland, and around Rathke’s cleft in the fetal gland. However, the organisation differed, with larger groups of cells enclosed within a single basement membrane. Possible vascular connections demonstrated between the posterior lobe and the intermediate zone would permit access of posterior lobe hormones to this zone. Our data confirmed disruption of expression in pituitary adenomas, type IV collagen, laminin and β₄ integrin having a mainly perivascular distribution, with more variable immunoreactivity for fibronectin. Received: 17 February 1997 / Accepted: 17 May 1997     

Neural-specific inactivation of ShcA functions results in anatomical disorganization of subventricular zone neural stem cell niche in the adult brain

Shc(s) family of adaptor molecules has been implicated in several physiological functions. In particular, our previous studies have shown major roles in the mechanisms that control the transition from proliferating neural stem cells (NSCs) to postmitotic neurons in the mammalian brain. In the adult brain, ShcA expression is mainly restricted to a subpopulation of cells in the subventricular zone (SVZ) neurogenic area, enlightening a potential role for this molecule in the establishment/maintenance of this adult NSC niche. In order to investigate this matter, here we took advantage of Cre/lox technology with the purpose of interfering with (or delete) ShcA function in nestin-expressing neural progenitors in vivo. Our analyses revealed signs of anatomical disorganization in the adult brain at the boundary between the striatum and the corpus callosum and reduced thickness both at the ventricular level and through the rostral migratory stream. Analysis of cell proliferation and cell death unveiled a prominent reduction of the former and no substantial alterations of the latter. Ultrastructural studies showed SVZ anatomical disarray and manifest variation in the SVZ cell type composition. In conclusion, these results provide evidence for a role of ShcA in the assembly and/or maintenance of the SVZ NSC niche in the adult brain.     

小鼠胚胎脑组织移植块中选择性荧光标记神经元的发育和投射

目的:建立选择性荧光标记小鼠胚胎脑组织移植块移植模型并观察选择性荧光标记的神经元在成体脑组织中的存活、发育和投射。方法:将孕龄14～15 d选择性荧光标记的胎鼠脑组织块移植到受损的普通小鼠大脑皮层中,2个月后用荧光显微镜和共聚焦显微镜结合Nissl染色的方法观察胚胎脑组织移植块内选择性荧光标记的神经元在受体大脑中的生长发育情况。结果:在胚胎脑组织移植块内观察到只有少部分神经元被标记,这些类似于Golgi染色模式的选择性荧光标记的神经元有大量的神经纤维投射到受体鼠的不同脑区。通过Nissl染色和共聚焦成像发现胚胎脑组织移植块内神经元能分化并形成典型的突触结构-树突棘和突触终扣。结论:胚胎脑组织移植块内选择性荧光标记的神经元在受体脑内能够存活并特异性地表达荧光,这些标记的神经元具有正常的形态结构,可以投射到各个脑区并参与神经回路的重建。     

Down-regulation of the axonal polysialic acid-neural cell adhesion molecule expression coincides with the onset of myelination in the human fetal forebrain

The polysialic acid (PSA) modification of neural cell adhesion molecule, which reduces neural cell adhesion molecule (NCAM) - mediated cell adhesion, is involved in several developmental processes, such as cell migration, axonal growth, path finding, and synaptic plasticity. It has been suggested that PSA-NCAM expression may inhibit myelination. To clarify the relationship between myelination and the expression of PSA-NCAM we systematically investigated its expression in the human forebrain from embryonic stage to midgestation (19-24 gestation weeks, gw). Immunofluorescence on cryosections showed that PSA-NCAM is expressed at the earliest stage studied (5.5 gw) in the primordial plexiform layer of the telencephalon, which mainly consists of neuronal processes. At midgestation, cortical axonal tracts in the emerging white matter were PSA-NCAM+, but they were not yet myelinated, based on the lack of myelin basic protein (MBP) immunoreaction. To follow the progression of myelination we developed organotypic slice cultures that included the subventricular and intermediate zones of the fetal forebrain. In freshly prepared slices, similar to cryosections, axonal tracts were PSA-NCAM+ but did not express MBP. After 5 days in culture there was a dramatic increase in MBP expression around the axons of the intermediate zone, which suggested the onset of myelination. Simultaneously with MBP up-regulation PSA-NCAM expression in axons was completely lost, as demonstrated both with immunofluorescence and Western blot analysis. These results support the idea that in the human fetal forebrain axonal PSA-NCAM expression is inversely related to primary myelination.     

Pregnancy: The expression of c-kit protein in human adult and fetal tissues

The c-kit proto-oncogene encodes a tyrosine kinase receptorand is allelic with the dominant white-spotting (W) locus ofthe mouse. In this study we investigated the expression of humanc-kit protein in various adult and fetal human tissues immunohistochemicallyusing anti-human c-kit monoclonal antibody. To discriminatec-kit+ cells from mast cells expressing c-kit, mast cells wereidentified by staining with Toluidine blue. In oogonia, spermatogoniaand skin melanocytes of the fetus and in oocytes of adult ovary,c-kit expression was detected. In adult uterus, c-kit+ cellswere widely distributed in the basal layer of the endometrium,myometrium and cervix, the number and distribution being almostidentical to those of mast cells. In fetal uterus, c-kit+ non-mastcells clustered beneath the epithelium and a few mast cellswere observed in the myometrium and subserosal layer. In bothadult and fetus, c-kit+ non-mast cells were detected withinsmooth muscle layers of the intestine, colon and oesophagus,while mast cells were observed in the mucosal and submucosallayers of these organs. In contrast to mice, no expression ofc-kit protein was detected in the human placenta and decidua.Thus, the distribution of c-kit+ cells in various tissues issimilar but not identical between adult and fetus and betweenhuman and mouse.     

Gender and age related changes in number of dopaminergic neurons in adult human olfactory bulb

IntroductionDopamine is one of the major brain neurotransmitters, and the loss of dopaminergic neurons in basal ganglia cause motor deficits in Parkinson's disease. We proposed that the difficulty in olfaction observed in the elderly may be due to an alteration in the number of dopaminergic neurons.Materials and methodsSections were taken from olfactory bulbs of post-mortem tissue specimens of 13 humans, males and females, aged from 19 to 63 years (≤35 and ≥50 years), with no history of neurological disorders. The tissues were fixed, embedded, cut on a freezing microtome, and prepared for immunohistochemical analysis using tyrosine hydroxylase (TH) and aromatic l-amino acid decarboxylase (AADC) antibodies. The number of positive neurons was counted.ResultsTH- and AADC-positive cells were present in the glomerular layer. There was no significant difference between the numbers of TH- and AADC-positive cells, in males and females, and in young and elderly individuals. The quantitative analysis revealed that the number of TH- and AADC-positive neurons were significantly higher in males than in females (P < 0.05). Moreover, there was a significant increase in the number of TH- and AADC-positive neurons in the olfactory bulbs of the elderly compared with young individuals (P < 0.05).ConclusionFactors such as gender and age may affect the number of dopaminergic neurons, and there is a correlation between increased dopaminergic neurons and olfactory performance. Moreover, the increase in dopaminergic cells in the olfactory bulb of the elderly may indicate the existence of rostral migratory stream in adult humans.     

Different physiological properties of spontaneous excitatory postsynaptic currents in nucleus accumbens shell neurons between adult and juvenile rats

Studies have demonstrated the changes of the physiological characteristics of nucleus accumbens (NAc) neurons with the postnatal development of rats. In the present study, spontaneous excitatory postsynaptic currents (sEPSCs) were recorded in the slices of NAc shell (NAcS) of adult and juvenile rats. Our results demonstrate that both the average amplitude of sEPSCs and the average frequency of sEPSCs in the NAcS slices of adult rats decreased significantly than that in juvenile rats. The average half width of sEPSCs in the NAcS slices in adult rats increased significantly than that in juvenile rats. The rise time of sEPSCs, the rise 50 time of sEPSCs and the 10–90 rise time of sEPSCs in the NAcS slices increased significantly in adult rats than that in juvenile rats. The decay time of sEPSCs in the NAcS slices also increased significantly in adult rats than that in juvenile rats. The above results strongly indicate that there are marked changes in the electrophysiological properties of single sEPSC in the NAcS slices of juvenile and adult rats.     

Abl expression in human fetal and adult tissues,tumours and tumour microvessels

Abl kinases encoded by the abl oncogenes inhibit apoptosis without affecting cell proliferation. The aim of this study was to examine a wide range of normal fetal and adult human tissues and a variety of tumour types for Abl immunoreactivity. Sections from 193 paraffin blocks of normal fetal and adult tissues and 72 blocks from representative tumours were stained immunohistochemically using a polyclonal antibody to c-Abl/Bcr–Abl oncoprotein. Weak Abl immunoreactivity was observed in many adult tissues. Moderately intense or strong staining (cytoplasmic, nuclear or membranous) was consistently seen in hyaline cartilage, adipocytes, and ciliated epithelium. In fetal tissues, there was a broadly similar staining pattern, but Abl expression was also seen in muscle (all types) and occasionally in endothelial cells. The most intense staining was seen in sites of endochondral ossification and in the umbilical cord stroma. Negatively staining tissues included epidermis and squamous mucosa, lymph nodes, tonsil, spleen, hepatocytes, and adrenals. Most tumours showed focal or weak Abl immunoreactivity. The most intense staining was seen in chondrosarcoma, liposarcoma, and diffuse gastric (signet ring) adenocarcinoma. In the latter two tumour types, Abl expression was also observed in tumour microvessels. These results suggest that Abl not only functions as an apoptosis inhibitor, but also may have a role in connective tissue maturation and differentiation and in tumour growth and angiogenesis. © 1997 John Wiley & Sons, Ltd.     

Number of germ cells and somatic cells in human fetal ovaries during the first weeks after sex differentiation

BACKGROUND: This study presents the number of germ cells and somatic cells in human fetal ovaries during week 6 to week 9 post conception, i.e. the first weeks following sex differentiation of the gonads. METHODS: One ovary with attached mesonephros from each of 11 individual legal abortions was used for estimation of cell numbers. After recovery of the fetus, the ovary-mesonephric complexes were immediately isolated, fixed and processed for histology. A stereological method was utilized to estimate the total number of oogonia in all ovaries and somatic cells in seven of them. RESULTS: The number of oogonia per ovary increased from approximately 26,000 in week 6 to approximately 250,000 in week 9 and somatic cells from approximately 240,000 to approximately 1.4 x 10(6). The ratio of oogonia to somatic cells tended to increase throughout the period. The concentration of oogonia was similar in the cranial (mesonephric connected) part and the caudal part of the ovaries. CONCLUSIONS: This is the first stereological estimation of the number of oogonia and somatic cells in human fetal ovaries, and the first estimation of germ cells and somatic cells in ovaries aged <9 weeks. The number of oogonia in week 9 is comparable to the numbers previously published based on non-stereological estimations. We found early stages of meiosis in fetal ovaries from week 9.     

Number of germ cells and somatic cells in human fetal testes during the first weeks after sex differentiation

BACKGROUND: This study presents the number of germ cells and somatic cells in human fetal testes during week 6 to week 9 post conception, i.e. the first weeks following sex differentiation of the testes. METHODS: One testis with attached mesonephros from each of 10 individual legal abortions was used. After recovery of the fetus, the testes were immediately isolated, fixed and processed for histology. The optical fractionator technique, a stereological method, was utilized to estimate the total number of germ cells in ten testes and somatic cells in six of them. RESULTS: The number of germ cells per testis increased from approximately 3000 in week 6 to approximately 30000 in week 9. The ratio of germ cells to Sertoli cells was approximately 1:11 and the ratio of germ cells to somatic cells was approximately 1:44 throughout this period. CONCLUSIONS: For the first time, germ cell and somatic cell number have been determined during early human fetal testis development. Knowledge of the number of germ cells in this period may be very important, because several environmental pollutants are suspected to result in decreased semen quality in men born of mothers exposed to these pollutants during pregnancy.