The effect on congenital heart diseases of maternal EPHX1 polymorphisms modified by polycyclic aromatic hydrocarbons exposure.

Polycyclic aromatic hydrocarbons (PAHs) may be 1 of etiologic factors responsible for congenital heart diseases (CHDs). Variations of the microsomal epoxide hydrolase (EPHX1) gene, as well as their possible interactions with PAHs exposure, may increase susceptibility to CHDs.This case-control study investigated the risk of CHDs in relation to the EPHX1 polymorphisms and assessed the interactions between these polymorphisms and PAHs exposure in 357 mothers of CHDs fetuses and 270 control mothers. Logistic regression models for the risk of CHDs were applied to determine the effect of genetic polymorphisms using additive, recessive, and dominant genetic models, as well as gene-exposure interactions. Multiple testing was adjusted by applying the false discovery rate (FDR).None of the maternal genetic polymorphisms of EPHX1 was associated with CHDs occurrence. Only the single nucleotide polymorphism rs1051740 was associated with an increased risk of right-sided obstructive malformations under the recessive model (adjusted odds ratio [aOR] = 1.852, 95% confidence interval [CI]: 1.065, 3.22) before FDR correction. A possible modifying effect of PAHs exposure on genetic polymorphisms of EPHX1 was found in susceptibility to CHDs, though no multiplicative-scale interactions between maternal exposure to PAHs and polymorphisms of EPHX1 gene were seento affect the risk of CHDs.The role of EPHX1 gene polymorphisms for CHDs need to be further evaluated, in particularly by interacting with PAHs exposure.

Experience of more than 100 preimplantation genetic diagnosis cycles for monogenetic diseases using whole genome amplification and linkage analysis in a single centre.

OBJECTIVE: To report the outcomes of more than 100 cycles of preimplantation genetic diagnosis for monogenetic diseases. DESIGN: Case series. SETTING: Tertiary assisted reproductive centre in Hong Kong, where patients needed to pay for the cost of preimplantation genetic diagnosis on top of standard in-vitro fertilisation charges. PATIENTS: Patients undergoing preimplantation genetic diagnosis for monogenetic diseases at the Centre of Assisted Reproduction and Embryology, Queen Mary Hospital-The University of Hong Kong between 1 August 2007 and 30 April 2014 were included. INTERVENTIONS: In-vitro fertilisation, intracytoplasmic sperm injection, embryo biopsy, and preimplantation genetic diagnosis. MAIN OUTCOME MEASURES: Ongoing pregnancy rate and implantation rate. RESULTS: Overall, 124 cycles of preimplantation genetic diagnosis were initiated in 76 patients, 101 cycles proceeded to preimplantation genetic diagnosis, and 92 cycles had embryo transfer. The ongoing pregnancy rate was 28.2% per initiated cycle and 38.0% per embryo transfer, giving an implantation rate of 35.2%. There were 16 frozen-thawed embryo transfer cycles in which, following preimplantation genetic diagnosis, cryopreserved embryos were replaced resulting in an ongoing pregnancy rate of 37.5% and implantation rate of 30.0%. The cumulative ongoing pregnancy rate was 33.1%. The most frequent indication for preimplantation genetic diagnosis was thalassaemia, followed by neurodegenerative disorder and cancer predisposition. There was no misdiagnosis. CONCLUSIONS: Preimplantation genetic diagnosis is a reliable method to prevent couples conceiving fetuses severely affected by known genetic disorders, with ongoing pregnancy and implantation rates similar to those for in-vitro fertilisation for routine infertility treatment.

Thanatophoric dysplasia. Correlation among bone X-ray morphometry, histopathology, and gene analysis.

OBJECTIVE: Documentation through X-ray morphometry and histology of the steady phenotype expressed by FGFR3 gene mutation and interpolation of mechanical factors on spine and long bones dysmorphism. MATERIALS AND METHODS: Long bones and spine of eight thanatophoric dysplasia and three age-matched controls without skeletal dysplasia were studied after pregnancy termination between the 18th and the 22nd week with X-ray morphometry, histology, and molecular analysis. Statistical analysis with comparison between TD cases and controls and intraobserver/interobserver variation were applied to X-ray morphometric data. RESULTS: Generalized shortening of long bones was observed in TD. A variable distribution of axial deformities was correlated with chondrocyte proliferation inhibition, defective seriate cell columns organization, and final formation of the primary metaphyseal trabeculae. The periosteal longitudinal growth was not equally inhibited, so that decoupling with the cartilage growth pattern produced the typical lateral spurs around the metaphyseal growth plates. In spine, platyspondyly was due to a reduced height of the vertebral body anterior ossification center, while its enlargement in the transversal plane was not restricted. The peculiar radiographic and histopathological features of TD bones support the hypothesis of interpolation of mechanical factors with FGFR3 gene mutations. CONCLUSIONS: The correlated observations of X-ray morphometry, histopathology, and gene analysis prompted the following diagnostic workup for TD: (1) prenatal sonography suspicion of skeletal dysplasia; (2) post-mortem X-ray morphometry for provisional diagnosis; (3) confirmation by genetic tests (hot-spot exons 7, 10, 15, and 19 analysis with 80-90% sensibility); (4) in negative cases if histopathology confirms TD diagnosis, research of rare mutations through sequential analysis of FGFR3 gene.

What is the evidence in humans that DNA methylation changes link events in utero and later life disease?

Development in utero is now recognized as crucial to determining later life disease susceptibility. Whilst mechanisms are poorly understood, there has been considerable interest in the potential role of epigenetic processes in intra-uterine programming of disease. Epigenetic modifications include various mechanisms that influence chromatin structure and gene expression. Here, we review emerging data from human studies that altered DNA methylation links intra-uterine events with later life disease. Further research in this field is needed to determine whether altered DNA methylation in target tissues can be used as a biomarker for the early identification of and intervention in individuals most at risk of later life disease.

Synaptic dysfunction in schizophrenia.

Schizophrenia alters basic brain processes of perception, emotion, and judgment to cause hallucinations, delusions, thought disorder, and cognitive deficits. Unlike neurodegeneration diseases that have irreversible neuronal degeneration and death, schizophrenia lacks agreeable pathological hallmarks, which makes it one of the least understood psychiatric disorders. With identification of schizophrenia susceptibility genes, recent studies have begun to shed light on underlying pathological mechanisms. Schizophrenia is believed to result from problems during neural development that lead to improper function of synaptic transmission and plasticity, and in agreement, many of the susceptibility genes encode proteins critical for neural development. Some, however, are also expressed at high levels in adult brain. Here, we will review evidence for altered neurotransmission at glutamatergic, GABAergic, dopaminergic, and cholinergic synapses in schizophrenia and discuss roles of susceptibility genes in neural development as well as in synaptic plasticity and how their malfunction may contribute to pathogenic mechanisms of schizophrenia. We propose that mouse models with precise temporal and spatial control of mutation or overexpression would be useful to delineate schizophrenia pathogenic mechanisms.

Schizophrenia as variation in the sapiens-specific epigenetic instruction to the embryo.

The psychoses (schizophrenia and bipolar disorder) occur in all populations with approximately uniform incidence and sex-dependent age of onset. Core symptoms involve aspects of language; brain structural deviations are sex and hemisphere-related. Genetic predisposition is unaccounted for by linkage or association. The hypothesis is proposed that the 'missing heritability' is epigenetic in form and generated in meiosis on a species-specific XY chromosomal template. A duplication from Xq21.3 to Yp11.2 that occurred 6 million years ago is proposed as critical to hominin evolution. Within this block of homology the Protocadherin11XY gene pair is expressed as a cell surface adhesion factor in both X and Y forms; it has undergone a series of coding changes (16 in the Y sequence and 5 in the X including two to cysteines) in the hominin lineage. According to the hypothesis these sequence changes, together with one or more deletions and a paracentric inversion in the Y block, were successively selected; late events in this series established cerebral asymmetry (the 'torque') as the defining characteristic of the human brain. Built around this reference frame, an epigenetic message channels early development of the embryo in a sapiens-specific format. Diversity in meiotic pairing is postulated as the basis for species-specific deviations in development associated with psychosis.

Frontoparietal connectivity in substance-naïve youth with and without a family history of alcoholism.

Frontoparietal connections underlie key executive cognitive functions. Abnormalities in the frontoparietal network have been observed in chronic alcoholics and associated with alcohol-related cognitive deficits. It remains unclear whether neurobiological differences in frontoparietal circuitry exist in substance-naïve youth who are at-risk for alcohol use disorders. This study used functional connectivity magnetic resonance imaging and diffusion tensor imaging to examine frontoparietal connectivity and underlying white matter microstructure in 20 substance-naïve youth with a family history of alcohol dependence and 20 well-matched controls without familial substance use disorders. Youth with a family history of alcohol dependence showed significantly less functional connectivity between posterior parietal and dorsolateral prefrontal seed regions (ps<.05), as compared to family history negative controls; however, they did not show differences in white matter architecture within tracts subserving frontoparietal circuitry (ps>.34). Substance-naïve youth with a family history of alcohol dependence show less frontoparietal functional connectivity in the absence of white matter microstructural abnormalities as compared to youth with no familial risk. This may suggest a potential neurobiological marker for the development of substance use disorders.

Maternal interleukin-6 (-174) C/C polymorphism is associated with chorioamnionitis and cystic periventricular leucomalacia of the preterm infant.

OBJECTIVE: To evaluate the association between maternal interleukin (IL)-6 G(-174)C polymorphism and cystic periventricular leukomalacia (cPVL) of the preterm newborn. STUDY DESIGN: After searching a local database, we recruited 132 preterm infants with diagnosis of cPVL, 44 Caucasian mothers were also recruited to participate in this candidate gene-association study at a single teritary care center. Data related to maternal IL-6 G(-174)C polymorphisms were compared with 41 controls, and furthermore compared with data from umbilical cord blood samples from a consecutive birth cohort of 395 healthy newborns, and published data from Caucasian populations including 1104 adults, respectively. In addition, subgroup analysis was performed in cases with either history of preterm premature rupture of the membranes (PPROM) or clinical chorioamnionitis (CCA). IL-6 genotyping was performed using an allele-specific polymerase chain reaction technique. RESULT: Frequencies of the IL-6 G(-174)C polymorphisms did not differ between cases (GG, 29.5%; GC, 54.5% and CC, 15.9%) and controls (GG, 34.2; GC, 51.2 and CC, 14.6%). Subgroup analysis of 31 cases with history of PPROM (GG, 25.8; GC, 54.8 and CC 19.4%) and controls did not reveal significant differences, but a significantly higher frequency of the CC genotype was found in 23 cases with a history of CCA (34.8%) compared with controls by either univariate (P=0.032; odds ratio 3.11, 95% confidence interval (CI) 1.11 to 8.68) or multivariate analysis (P=0.049, odds ratio 2.54, 95% CI 1.01 to 6.45). These data were confirmed by a comparing the CC genotype frequency to 395 term controls (CC 14.7%, P=0.005) and to the mean CC genotype frequency of 1104 Caucasian adults (CC 15.6%, P<0.0001). CONCLUSION: Frequencies of the IL-6 G(-174)C polymorphisms did not differ between groups. Subgroup analysis revealed an association of the CC genotype with CCA and cPVL in the preterm newborn.

Biology of vascular malformations of the brain.

BACKGROUND AND PURPOSE: This review discusses recent research on the genetic, molecular, cellular, and developmental mechanisms underlying the etiology of vascular malformations of the brain (VMBs), including cerebral cavernous malformation, sporadic brain arteriovenous malformation, and the arteriovenous malformations of hereditary hemorrhagic telangiectasia. Summary of Review- The identification of gene mutations and genetic risk factors associated with cerebral cavernous malformation, hereditary hemorrhagic telangiectasia, and sporadic arteriovenous malformation has enabled the development of animal models for these diseases and provided new insights into their etiology. All of the genes associated with VMBs to date have known or plausible roles in angiogenesis and vascular remodeling. Recent work suggests that the angiogenic process most severely disrupted by VMB gene mutation is that of vascular stabilization, the process whereby vascular endothelial cells form capillary tubes, strengthen their intercellular junctions, and recruit smooth muscle cells to the vessel wall. In addition, there is now good evidence that in some cases, cerebral cavernous malformation lesion formation involves a genetic 2-hit mechanism in which a germline mutation in one copy of a cerebral cavernous malformation gene is followed by a somatic mutation in the other copy. There is also increasing evidence that environmental second hits can produce lesions when there is a mutation to a single allele of a VMB gene. CONCLUSIONS: Recent findings begin to explain how mutations in VMB genes render vessels vulnerable to rupture when challenged with other inauspicious genetic or environmental factors and have suggested candidate therapeutics. Understanding of the cellular mechanisms of VMB formation and progression in humans has lagged behind that in animal models. New knowledge of lesion biology will spur new translational work. Several well-established clinical and genetic database efforts are already in place, and further progress will be facilitated by collaborative expansion and standardization of these.

Abnormalities in the myeloid progenitor compartment in Down syndrome fetal liver precede acquisition of GATA1 mutations.

Down syndrome (DS) children have a high frequency of acute megakaryoblastic leukemia (AMKL) in early childhood. At least 2 in utero genetic events are required, although not sufficient, for DS-AMKL: trisomy 21 (T21) and N-terminal-truncating GATA1 mutations. To investigate the role of T21 in DS-AMKL, we compared second trimester hemopoiesis in DS without GATA1 mutations to gestation-matched normal controls. In all DS fetal livers (FLs), but not marrows, megakaryocyte-erythroid progenitor frequency was increased (55.9% +/- 4% vs 17.1% +/- 3%, CD34(+)CD38(+) cells; P < .001) with common myeloid progenitors (19.6% +/- 2% vs 44.0% +/- 7%) and granulocyte-monocyte (GM) progenitors (15.8% +/- 4% vs 34.5% +/- 9%) commensurately reduced. Clonogenicity of DS-FL versus normal FL CD34(+) cells was markedly increased (78% +/- 7% vs 15% +/- 3%) affecting megakaryocyte-erythroid ( approximately 7-fold higher) and GM and colony-forming unit-granulocyte, erythrocyte macrophage, megakaryocyte (CFU-GEMM) progenitors. Replating efficiency of CFU-GEMM was also markedly increased. These data indicate that T21 itself profoundly disturbs FL hemopoiesis and they provide a testable hypothesis to explain the increased susceptibility to GATA1 mutations in DS-AMKL and DS-associated transient myeloproliferative disorder.

Sex-differences in grey-white matter structure in normal-reading and dyslexic adolescents.

MR images were used to look for brain structure irregularities in adolescent children with dyslexia by use of combined grey and white matter volume measurements and fractal dimension (FD) of the grey-white matter border. The data were collected from 13 dyslexic adolescent (8 boys and 5 girls) that were compared with 18 control subjects (8 boys and 10 girls). The MR images were first segmented, and the volume as well as the FD of the grey/white matter border for the whole brain and for each hemisphere was computed. Changes were found in the measured volumes of both grey and white matter and were best reflected in the ratio of grey/white matter and in FD values, especially in the left hemisphere. The results showed that, although dyslexia is less frequent in women, the structural differences in the brain are more pronounced in their case, pointing to an increased vulnerability of the female brain to morphological changes associated with dyslexia.

Fetal and neonatal pathways to obesity.

Evolutionary and developmental perspectives add considerably to our understanding of the aetiology of obesity and its related disorders. One pathway to obesity represents the maladaptive consequences of an evolutionarily preserved mechanism by which the developing mammal monitors nutritional cues from its mother and adjusts its developmental trajectory accordingly. Prediction of a nutritionally sparse environment leads to a phenotype that promotes metabolic parsimony by favouring fat deposition, insulin resistance, sarcopenia and low energy expenditure. But this adaptive mechanism evolved to accommodate gradual changes in nutritional environment; rapid transition to a situation of high energy density results in a mismatch between predicted and actual environments and increased susceptibility to metabolic disease. This pathway may also explain why breast and bottle feeding confer different risks of obesity. We discuss how early environmental signals act through epigenetic mechanisms to alter metabolic partitioning, glucocorticoid action and neuroendocrine control of appetite. A second pathway involves alterations in fetal insulin levels, as seen in gestational diabetes, leading to increased prenatal fat mass which is subsequently amplified by postnatal factors. Both classes of pathway may coexist in an individual. This developmental approach to obesity suggests that potential interventions will vary according to the target population.

Developmental and epigenetic pathways to obesity: an evolutionary-developmental perspective.

Although variation in individual lifestyle and genotype are important factors in explaining individual variation in the risk of developing obesity in an obesogenic environment, there is growing evidence that developmentally plastic processes also contribute. These effects are mediated at least in part through epigenetic processes. These developmental pathways do not directly cause obesity but rather alter the risk of an individual developing obesity later in life. At least two classes of developmental pathway are involved. The mismatch pathway involves the evolved adaptive responses of the developing organism to anticipated future adverse environments, which have maladaptive consequences if the environment is mismatched to that predicted. This pathway can be cued by prenatal undernutrition or stresses that lead the organism to forecast an adverse future environment and change its developmental trajectory accordingly. As a result, individuals develop with central and peripheral changes that increase their sensitivity to an obesogenic environment. It provides a model for how obesity emerges in populations in rapid transition, but also operates in developed countries. There is growing experimental evidence that this pathway can be manipulated by, for example, postnatal leptin exposure. Secondly, maternal diabetes, maternal obesity and infant overfeeding are associated with a greater risk of later obesity. Early life offers a potential point for preventative intervention.

Early pre-implantation lethality in mice carrying truncated mutation in the RNA polymerase 1-2 gene.

Ribosomal DNA (rDNA) transcription by RNA polymerase I (Pol I) is an important initial step for the production of ribosomes. The RNA polymerase 1-2 (Rpo1-2) gene is comprised of 15 exons and encodes 1135 amino acids (aa) of the second largest subunit in Pol I. In a gene trap screen, we have identified an insertional mutation (Rpo1-2(Gt)) in the 14th exon of Rpo1-2, resulting in a truncation of 312aa from the C-terminal. In Rpo1-2(Gt/Gt) embryos, the synthesis of rRNA was severely impaired. Rpo1-2(Gt/Gt) embryos could develop to the morula stage, and thereafter displayed nucleolus disruption and apoptotic cell death. These results indicate that the loss of rDNA transcription induced nucleolar structure disorganization and apoptosis in preimplantation embryos.

Neurodevelopment in seizure-prone and seizure-resistant rat strains: recognizing conflicts in management.

Cytoarchitectural alterations during central nervous system (CNS) development are believed to underlie aberrations in brain morphology that lead to epilepsy. We have recently reported marked reductions in hippocampal and white matter volumes along with relative ventriculomegaly in a rat strain bred to be seizure-prone (FAST) compared to a strain bred to be seizure-resistant (SLOW) (Gilby et al., 2002, American Epilepsy Society 56th Annual Meeting). This study was designed to investigate deviations in gene expression during late-phase embryogenesis within the brains of FAST and SLOW rats. In this way, we hoped to identify molecular mechanisms operating differentially during neurodevelopment that might ultimately create the observed differences in brain morphology and/or seizure susceptibility. Using Superarray technology, we compared the expression level of 112 genes, known to play a role in neurodevelopment, within whole brains of embryonic day 21 (E21) FAST and SLOW rats. Results revealed that while most genes investigated showed near equivalent expression levels, both Apolipoprotein E (APOE) and the beta2 subunit of the voltage-gated sodium channel (SCN2beta) were significantly underexpressed in brains of the seizure-prone embryos. Currently, these transcripts have no known interactions during embryogenesis; however, they have both been independently linked to seizure disposition and/or neurodevelopmental aberrations leading to epilepsy. Thus, alterations in the timing and/or degree of expression for APOE and SCN2beta may be important to developmental cascades that ultimately give rise to the differing brain morphologies, behaviors, and/or seizure vulnerabilities that characterize these strains.

Lung development and susceptibility to chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease with emphysema has been considered to be an accelerated involutional disease of aging smokers. However, because only a proportion ( approximately 15%) of smokers develop chronic obstructive pulmonary disease with emphysema, clearly genetic susceptibility must play a significant part in determining both the age of onset and the rapidity of decline in lung function. In mice, interference with key genes, either by null mutation, hypomorphism, or gain or loss of function, results in phenotypes comprising either neonatal lethal respiratory distress if the structural effect is severe, or reduced alveolarization and/or early-onset emphysema if the effect is milder. Likewise, null mutants that interfere with matrix assembly and/or integrity, such as elastin, lysyl oxidase, or fibrillin, also result in alveolar dysplasia. Importantly, null mutation of Smad3, which encodes a receptor-activated Smad in the transforming growth factor-beta signaling pathway, results in a more subtle failure to correctly organize the alveolar matrix, which is in turn antecedent to early-onset emphysema mediated by matrix metalloproteinase-9. Furthermore, exposure to side-stream smoke profoundly exacerbates and accelerates alveolar destruction, leading to more severe early-onset emphysema in young Smad3-null mice (unpublished data). Interestingly, polymorphisms in the fibrillin, transforming growth factor-beta type II receptor, and matrix metalloproteinase-9 genes have been described in humans with emphysema. Thus, dysplastic or degraded matrix cannot provide the structural niche for alveolar stem/progenitor cells to assume the correct phenotype and/or repair the alveolar cell lineage niche. The hope is that providing the correct exogenous signals can coax them into doing so.

Early signs of motoneuron vulnerability in a disease model system: Characterization of transverse slice cultures of spinal cord isolated from embryonic ALS mice.

Mutations in the SOD1 gene are associated with familial amyotrophic lateral sclerosis. The mechanisms by which these mutations lead to cell loss within the spinal cord ventral horns are unknown. In the present report we used the G93A transgenic mouse model of amyotrophic lateral sclerosis to develop and characterize an in vitro tool for the investigation of subtle alterations of spinal tissue prior to frank neuronal degeneration. To this aim, we developed organotypic slice cultures from wild type and G93A embryonic spinal cords. We combined immunocytochemistry and electron microscopy techniques to compare wild type and G93A spinal cord tissues after 14 days of growth under standard in vitro conditions. By SMI32 and choline acetyl transferase immunostaining, the distribution and morphology of motoneurons were compared in the two culture groups. Wild type and mutant cultures displayed no differences in the analyzed parameters as well as in the number of motoneurons. Similar results were observed when glial fibrillary acidic protein and myelin basic protein-positive cells were examined. Cell types within the G93A slice underwent maturation and slices could be maintained in culture for at least 3 weeks when prepared from embryos. Electron microscopy investigation confirmed the absence of early signs of mitochondria vacuolization or protein aggregate formation in G93A ventral horns. However, a significantly different ratio between inhibitory and excitatory synapses was present in G93A cultures, when compared with wild type ones, suggesting the expression of subtle synaptic dysfunction in G93A cultured tissue. When compared with controls, G93A motoneurons exhibited increased vulnerability to AMPA glutamate receptor-mediated excitotoxic stress prior to clear disease appearance. This in vitro disease model may thus represent a valuable tool to test early mechanisms contributing to motoneuron degeneration and potential therapeutic molecular interventions.

Making waves in cancer research: new models in the zebrafish.

The zebrafish (Danio rerio) has proven to be a powerful vertebrate model system for the genetic analysis of developmental pathways and is only beginning to be exploited as a model for human disease and clinical research. The attributes that have led to the emergence of the zebrafish as a preeminent embryological model, including its capacity for forward and reverse genetic analyses, provides a unique opportunity to uncover novel insights into the molecular genetics of cancer. Some of the advantages of the zebrafish animal model system include fecundity, with each female capable of laying 200-300 eggs per week, external fertilization that permits manipulation of embryos ex utero, and rapid development of optically clear embryos, which allows the direct observation of developing internal organs and tissues in vivo. The zebrafish is amenable to transgenic and both forward and reverse genetic strategies that can be used to identify or generate zebrafish models of different types of cancer and may also present significant advantages for the discovery of tumor suppressor genes that promote tumorigenesis when mutationally inactivated. Importantly, the transparency and accessibility of the zebrafish embryo allows the unprecedented direct analysis of pathologic processes in vivo, including neoplastic cell transformation and tumorigenic progression. Ultimately, high-throughput modifier screens based on zebrafish cancer models can lead to the identification of chemicals or genes involved in the suppression or prevention of the malignant phenotype. The identification of small molecules or gene products through such screens will serve as ideal entry points for novel drug development for the treatment of cancer. This review focuses on the current technology that takes advantage of the zebrafish model system to further our understanding of the genetic basis of cancer and its treatment.

An evaluation of selected human eye dimensions at different periods of the foetal life.

In the course of myopia many anatomical changes in the structure of the eyeball take place. These changes surface during early childhood. It is unclear if these changes form during the stage of foetal life. The aim of the paper was to examine whether changes which predestine to the formation of myopia occur during the prenatal period. 26 eyeballs of humans aged between 4 and 8 months of foetal life, fixed in a 10% solution of formalin were examined. The axial, equatorial and corneal dimensions were measured with Vernier calipers. The data were elaborated statistically by the Student t test, the significance level being p < 0.05. It was observed that in the course of maturation the axial length, equatorial and corneal diameter of the foetal eye increase. It was also observed that the dimensions of the eyeball expand symmetrically in all directions. This indicates that there is no predisposition to the development of myopia in the period of prenatal life.