Pleomorphism and drug resistant cancer stem cells are characteristic of aggressive primary meningioma cell lines.

BACKGROUND: Meningioma tumors arise in arachnoid membranes, and are the most reported central nervous system (CNS) tumors worldwide. Up to 20% of grade I meningioma tumors reoccur and currently predictive cancer stem cells (CSCs) markers for aggressive and drug resistant meningiomas are scarce. METHODS: Meningioma tissues and primary cell lines were investigated using whole transcriptome microarray analysis, immunofluorescence staining of CSCs markers (including CD133, Sox2, Nestin, and Frizzled 9), and drug treatment with cisplatin or etoposide. RESULTS: Unsupervised hierarchical clustering of six meningioma samples separated tissues into two groups. Analysis identified stem cells related pathways to be differential between the two groups and indicated the de-regulation of the stem cell associated genes Reelin (RELN), Calbindin 1 (CALB1) and Anterior Gradient 2 Homolog (AGR2). Immunofluorescence staining for four tissues confirmed stemness variation in situ. Biological characterization of fifteen meningioma primary cell lines concordantly separated cells into two functionally distinct sub-groups. Pleomorphic cell lines (NG type) grew significantly faster than monomorphic cell lines (G type), had a higher number of cells that express Ki67, and were able to migrate aggressively in vitro. In addition, NG type cell lines had a lower expression of nuclear Caspase-3, and had a significantly higher number of CSCs co-positive for CD133+ Sox2+ or AGR2+ BMI1+. Importantly, these cells were more tolerant to cisplatin and etoposide treatment, showed a lower level of nuclear Caspase-3 in treated cells and harbored drug resistant CSCs. CONCLUSION: Collectively, analyses of tissues and primary cell lines revealed stem cell associated genes as potential targets for aggressive and drug resistant meningiomas.

Deciphering the Significance of Plasma Chemokines as Prognostic Biomarkers in Pegylated IFN-Α-2a /Ribavirin-Treated Chronic Hepatitis C Genotype 4 Patients.

BACKGROUND: Hepatitis C viral (HCV) infection is a major clinical burden globally. Pegylated IFN-α-2a (PEG-IFN-α-2a) with ribavirin (RIB) therapy induces an array of cellular antiviral responses, including dsRNA kinases (PKR), chemokines, and cytokines to tackle the HCV infection. However, many HCV patients develop resistance to PEG-IFN/RIB therapy rendering the therapy ineffective. OBJECTIVES: Here, we assess the significance of chemokines in response to PEG-IFN-α-2a with ribavirin (PEG-IFN/RIB) therapy. METHODS: Twenty patients with HCV infection and ten healthy controls were enrolled in this study and patients were categorized into two groups 1), HCV-Responder (HCV-R), and 2) HCV-non-responder (HCV-NR). We analyzed IP-10, MIG, MCP-1, EOTAXIN, RANTES, IL-8, MIP-1a, and MIP-1b by a magnetic bead-based multiplex immunoassay approach based on Luminex X-MAP multiplex technology, using a MAGPIX instrument (Luminex Corporation, USA). RESULTS: A significant elevation of ALT and AST enzymes was observed in HCV-NR. Besides, the PEG-IFN/RIB therapy in both MIG and MCP-1 in HCV-NR patients was significantly induced. PEGIFN/ RIB therapy significantly increased the levels of chemokines, such as IL-8, IP-10, EOTAXIN, MIG, RANTES, and MIP-1ß, in HCV-R, indicating the chemokine response to PEG-IFN/RIB therapy. CONCLUSION: Hence, MCP-1 and MIG could be the potential biomarkers in HCV-NR and might be associated with the development of liver fibrosis, liver failure, and hepatocellular carcinoma. LIMITATIONS: Our study has only twenty samples of PEG-IFN/RIB treated HCV patients. This might be the reason for the lack of association between some of the inflammatory markers evaluated and the SVR, therefore, the association found between the chemokine levels observed in the plasma of HCV-R and HCV-NR and EVR cannot be extrapolated to patients infected with other HCV genotypes.

Neuroectodermal stem cells: A remyelinating potential in acute compressed spinal cord injury in rat model.

The outcomes of compressed spinal cord injury (CSCI) necessitate radical treatment. The therapeutic potential of neuroectodermal stem cells (NESCs) in a rat model of CSCI in acute and subacute stages was assessed. White Wistar rat were divided into control, sham-operated, CSCI untreated model, CSCI grafted with NESCs at 1 day after CSCI, and at 7 days after CSCI. Primary NESC cultures were prepared from brains of embryonic day 10 (E10) mice embryos. NESCs were transplanted at the site of injury using a Hamilton syringe. Locomotor functional assessment, routine histopathology, immunostaining for (GFAP), and ultrastructure techniques for evaluating the CSI were conducted. In CSCI, areas of hemorrhage, cavitation, reactive astrocytosis, upregulated GFAP expression of immunostained areas, degeneration of the axoplasm and demyelination were observed. One day after grafting with NESCs, a decrease in astrocyte reaction and pathological features, quantitative and qualitative enhancement of remyelination and improved locomotor activity were observed. Treatment with NESCs at 7 days after CSCI did not mitigatethe reactive astrocytosis and glial scar formation that hindered the ability of the NESCs to enhance remyelination of axons. In conclusion, the microenvironment and time of NESCs transplantation affect activity of astrocytes and remyelination of axons.

Histological, immunohistochemical and ultrastructural study of secondary compressed spinal cord injury in a rat model.

INTRODUCTION: Spinal cord injury (SCI) is a life-disrupting condition in which the first few days are the most critical. Secondary conditions remain the main causes of death for people with SCI. The response of different cell types to SCI and their role at different times in the progression of secondary degeneration are not well understood. The aim of this study was to study the histopathological changes of compressed spinal cord injury (CSCI) in a rat model. MATERIAL AND METHODS: Forty adult male Sprague-Dawley rats were divided into four groups. In group I, the rats were left without any surgical intervention (control). In group II, the rats were subjected to laminectomy without spinal cord compression (sham-operated). In group III, the rats were sacrificed one day after CSCI. In group IV, the rats were sacrificed seven days after CSCI. The light microscopy was employed to study the morphology using H&E, osmic acid staining and immunohistochemistry to detect glial fibrillary acidic protein (GFAP). The electron microscopy was applied for ultrastructure study. RESULTS: Histopathological examination of the posterior funiculus of the white matter revealed minute hemorrhages and localized necrotic areas on day 1, which transformed to areas of cavitation and fibrinoid necrosis surrounded by a demarcating rim of numerous astrocytes by day 7. The mean percentage of area of GFAP expression increased significantly by day 7. Osmic acid staining revealed swollen nerve fibers after one day, while numerous fibers had been lost by day 7. An ultrastructure study revealed swollen redundant thinned myelin and myelin splitting, as well as degeneration of axoplasm on day 1. On day 7, layers of the myelin sheath were folded and wrinkled with partial or complete demyelination areas. The myelin lamellae were disorganized and loose. The G-ratio was significantly greater on day 1 than day 7 after CSCI. CONCLUSIONS: In the rat model of CSCI details of the progressive spinal cord injury can be analyzed by morphological methods and may be helpful in the identification of the onset and type of clinical intervention.

HTLV-1 Associated Neurological Disorders.

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus which is endemic to certain regions of the world and infects around 10-20 million people. HTLV-1 is the etiologic agent of Adult T cell leukemia/lymphoma and HTLV-1 associated neurological disorders including mainly HTLV-1 associated myelopathy/Tropical spastic paraparesis. The involvement of the central nervous diseases occurs among: HTLV-1 infected patients from endemic areas, HIV positive individuals and drug users. The ability of HTLV-1 to cause associated neuropathies starts with the virus crossing the blood brain barrier (BBB), then entering and infecting the cells of the central nervous system. As a consequence, to the viral attack, HTLV-1 infected lymphocytes produce pro-inflammatory cytokines like tumor necrosis factor alpha, Interleukin 1 beta and interleukin 6 which further disrupts the BBB. Different serological tests have been used in the diagnosis of HTLV-1. These include: ELISA, Western Blotting (WB), Immunofluorescence, Particle Agglutination and Polymerase Chain Reaction which is used as a confirmatory test. Danazol, pentoxifylline, azathioprine and vitamin C have been used in the treatment of the HTLV-1 associated neurological disorders. Other antiviral drugs (lamivudine, zidovudine), monoclonal antibodies (Daclizumab) and therapeutic agents (valporic acid, interferons) have also been evaluated. No known drug, so far, has been shown to be efficacious. The aim of this review is to present the complexities of HTLV-1 associated neurological disorders and their current ongoing treatment. In addition to discussing future possible therapeutic strategies, by targeting HTVL-1 viral components and gene/s products, for the treatment of those neurological conditions.

Transcription factors regulating uspA genes in Catharanthus roseus.

RNA-Seq of the Catharanthus roseus SRA database was done in order to detect putative universal stress proteins (USPs) and their possible controlling factors. Previous analysis indicated the existence and characterization of uspA-like genes. In silico analysis of RNA-Seq database in several plant tissues revealed the possible functions and regulations of some uspA-like transcripts whose transcription factors (TFs) that might drive their expression were detected. BLAST indicated the existence of TF superfamilies erf (ethylene-responsive TF), bHLH (basic helix-loop-helix) and WRKY that might regulate several uspA-like genes. This data was proven via semi-quantitative RT-PCR in four plant tissues. Several of these transcription factor superfamilies are known for their action in the plant defense against biotic and abiotic stresses.

Immuno- and gene expression analysis of EGFR and Nestin during mice skin development.

BACKGROUND: Skin stem cell populations reside in the adult hair follicle, sebaceous gland, dermis and epidermis. However, the origin of most of the stem cell populations found in the adult epidermis is still unknown. Far more unknown is the embryonic origin of other stem cells that populate the other layers of this tissue. OBJECTIVES: The main objectives of the present study were to identify the precise anatomical localization of stem cells in mice during skin developing; and to determine the expression levels by using immuno- and gene expression analysis. SUBJECTS AND METHODS: In this comparative cross sectional study, six ages been chosen and divided into: embryonic days (E12.5, E14.5 and E19.5) and litter days (L7, L14 and L19). Skin were removed from the back side and processed to assess both immuno- and gene-expression of EGFR and Nestin surface antigen markers. Data of the different studied age groups was compared using the SPSS software. RESULTS: EGFR was mainly expressed in the outer root sheath (ORS), in basal and, to a lesser extent, in suprabasal keratinocytes and tend to lie where the dermis comes closest to the skin surface, while Nestin expressed throughout the dermis in the early embryo, but it is subsequently restricted to the follicular connective tissue sheaths later in development and to hair follicles after birth. Immunoexpression analysis showed a strong EGFR expression in all group ages except E12.5 which recorded as moderate, while Nestin showed strong expression level for all embryonic stages, while in the litters it was moderate. The qRT-PCR results were consistent with those of the immunohistochemical study. The Pearson correlation analyze present a correlation between the cases of study with age (p≤0.01), which indicated to the effect of age to mice development. CONCLUSION: EGFR and Nestin showed to have vital role during mice development, and considered to be suitable markers for the study of skin stem cells.

Updates on Therapeutics in Clinical Trials for Spinal Cord Injuries: Key Translational Applications of Human Embryonic Stem Cells-Derived Neural Progenitors.

Injuries to the spinal cord often have devastating physiological impacts due to the organ's vital role in neuro-impulse communications between muscles and the brain. Spinal Cord Injuries (SCIs) have recently been estimated to affect up to 80,000 individuals per year worldwide, with most occurring following a traumatic event. Unfortunately, effective treatments standardised globally for patients with SCIs have not yet been established. For many years, inadequate understanding of the complexities of the Central and Peripheral Nervous Systems and Neurogenesis has limited progression towards effective cures. However, in the last century, scientific advancements have generated new paradigms for medical treatments of SCIs. Basic as well as translational studies have progressed to such an extent that many kinds of protective and regenerative therapeutics are available in clinical trials. In particular, uncovering the mechanisms responsible for controlling the pluripotent state of Human Embryonic Stem Cells (hESCs) was proved vital for recognizing the prospective role in regenerative medicine for SCIs. Elucidating knowledge of neurogenesis alongside hESCs in relation to SCIs has been crucial for critical assessments of the existing translational therapeutic strategies for SCIs.

Effects of maternal age on the expression of mesenchymal stem cell markers in the components of human umbilical cord.

INTRODUCTION: Although the human umbilical cord (UC) has been previously considered a medical waste, its use as a main source of fetal stem cells for regenerative medicine applications has increased over the past few years. The aim of the study was to assess the impact of the maternal age on the expression of mesenchymal stem cells (MSC) markers CD105 and CD29 in the different areas of human UC. MATERIAL AND METHODS: In this comparative cross sectional study, one hundred term UCs from five maternal age groups (20-45 years) were collected after delivery from healthy mothers and were processed to assess both immuno- and gene expression of CD105 and CD29 surface antigen markers using immunohistochemical and RT-PCR techniques. RESULTS: The immunoexpression of CD105 and CD29 in the amniotic membrane (AM) and Wharton's jelly (WJ), the umbilical artery (UA) and the umbilical vein (UV) showed significant negative correlation with the maternal age (p < 0.001). Reduced amount of cells as well as the studied MSC markers and their gene expression levels were documented in older age mothers. CD105-positive MSCs were more abundant in the UA, whereas CD29-positive MSCs were more abundant in the AM and WJ. CONCLUSION: The decreased expression of CD105 and CD29 MSCs markers with age suggests that selective isolation of MSCs from Wharton's jelly, umbilical artery or umbilical vein of younger mothers should be recommended.

Cancer stem cells: a challenging paradigm for designing targeted drug therapies.

Despite earlier controversies about their role and existence within tumors, cancer stem cells (CSCs) are now emerging as a plausible target for new drug discovery. Research and development (R&D) efforts are being directed against key gene(s) driving initiation, growth, and metastatic pathways in CSCs and the tumor microenvironment (TME). However, the niche signals that enable these pluripotent CSCs to evade radio- and chemotherapy, and to travel to secondary tissues remain enigmatic. Small-molecule drugs, biologics, miRNA, RNA interference (RNAi), and vaccines, among others, are under active investigation. Here, we examine the feasibility of leveraging current knowhow of the molecular biology of CSCs and their cellular milieu to design futuristic, targeted drugs with potentially lower toxicity that can override the multiple drug-resistance issues currently observed with existing therapeutics.

Does the maternal age affect the mesenchymal stem cell markers and gene expression in the human placenta? What is the evidence?

BACKGROUND: Although the human placenta is considered medical wastes, it has become a main source of stem cells. Due to their easy isolation, ability to resist immune rejection and ability to differentiate into different types of adult cells, placental stem cells are considered superior to other stem cells. OBJECTIVES: This study aimed to assess the impact of the maternal age on the expression of mesenchymal stem cell (MSC) markers CD105 and CD29 in different areas of a term human placenta and to identify the differential expression of these markers in different placental areas. SUBJECTS AND METHODS: In this comparative cross sectional study, one hundred term placentas were collected after delivery from healthy mothers divided into five groups according to their age. Placentas were processed to assess both immune- and gene-expression of CD105 and CD29 surface antigen markers. Data of the different studied age groups was compared using the Statistical Package of Social Science (SPSS) software. RESULTS: CD105 and CD29 immunoexpression in decidua basalis, fetal membrane and placental villi showed significant negative correlations with the maternal age. CD105- and CD29-positive MSCs were significantly abundant in the decidua basalis and placental villi. Real-time polymerase chain reaction results were consistent with those of the immunohistochemical study. CONCLUSION: Labeling the placenta-driven MSCs with the specific area from which the cells were taken as well as the mother's age is advised and could be helpful in controlling the quality of the cell banks as well as the favorable outcome of the therapeutic applications.

Structural identification of putative USPs in Catharanthus roseus.

Nucleotide sequences of the C. roseus SRA database were assembled and translated in order to detect putative universal stress proteins (USPs). Based on the known conserved USPA domain, 24 Pfam putative USPA proteins in C. roseus were detected and arranged in six architectures. The USPA-like domain was detected in all architectures, while the protein kinase-like (or PK-like), (tyr)PK-like and/or U-box domains are shown downstream it. Three other domains were also shown to coexist with the USPA domain in C. roseus putative USPA sequences. These domains are tetratricopeptide repeat (or TPR), apolipophorin III (or apoLp-III) and Hsp90 co-chaperone Cdc37. Subsequent analysis divided USPA-like domains based on the ability to bind ATP. The multiple sequence alignment indicated the occurrence of eight C. roseus residues of known features of the bacterial 1MJH secondary structure. The data of the phylogenetic tree indicated several distinct groups of USPA-like domains confirming the presence of high level of sequence conservation between the plant and bacterial USPA-like sequences.

Histological and immunohistochemical effects of neuroectodermal cells transplantation after spinal cord injury in rats / Efectos histológicos e inmunohistoquímicos del trasplante de células neuroectodérmicas tras una lesión de la médula espinal en ratas

SUMMARY: In spinal cord injury, radical treatment is still a persistent hope for patients and clinicians. Our study aimed to determine the different histological changes in central, cranial and caudal sites of compressed spinal cord as a result of neuroectodermal stem cells (NESCs) transplantation in rats. For extraction of NESCs, future brains were extracted from mice embryos (10-days old) and cultured. Eighty, male rats were divided randomly into control, sham (20 rats each); while 40 rats were subjected to compressed spinal cord injury (CSCI). Seven days after spinal cord injury, rats were subdivided into 2 groups (20 rats each); an untreated and treated with NESCs injected cranial and caudal to the site of the spinal cord injury. Rats were sacrificed 4 weeks after transplantations of NESCs and specimens from the spinal cord at the central, cranial and caudal to site of spinal cord injury were proceeded to be stained with haematoxylin & eosin, osmic acid and Immunohistochemistry of glial fibrillary acidic protein (GFAP). Sections of CSCI revealed areas of hemorrhages, necrosis and cavitation limited by reactive astrocytosis, with upregulation of GFAP expression. Evidence of remyelination and mitigation of histopathological features, reactive astrocytosis in CSCI sections were more pronounced in cranial than in caudal region. NESCs transplantation ameliorated the pathological changes, promoted remyelination.

RESUMEN: En la lesión de la médula espinal, el tratamiento radical aún sigue siendo el tratamiento preferente para los pacientes y los médicos. El objetivo de este estudio fue determinar los diferentes cambios histológicos en los sitios centrales, craneales y caudales de la médula espinal comprimida, como resultado del trasplante de células madre neuroectodérmicas (NESCs) en ratas. Para la extracción de NESCs, se extrajeron y cultivaron los cerebros de embriones de ratones de 10 días de edad. Se dividieron 80 ratas macho aleatoriamente en grupos control, simulado (20 ratas cada una); mientras que 40 ratas fueron sometidas a lesión de la médula espinal comprimida (CSCI). Siete días después de la lesión de la médula espinal, las ratas se subdividieron en 2 grupos (20 ratas cada uno); un grupo no tratado y un grupo tratado con NESCs inyectado craneal y caudal en el sitio de la lesión. Las ratas fueron sacrificadas 4 semanas después de los trasplantes de NESCs y las muestras de la médula espinal en el centro, craneal y caudal del sitio de lesión fueron teñidas con hematoxilina y eosina, ácido ósmico e inmunohistoquímica de la proteína ácida fibrilar glial (GFAP). Las secciones de CSCI revelaron áreas de hemorragias, necrosis y cavitación limitadas por astrocitosis reactiva, con una regulación positiva de la expresión de GFAP. Evidencia de remielinización y mitigación de características histopatológicas, astrocitosis reactiva en secciones de CSCI fue más pronunciada en la región craneal que en la caudal. El trasplante de NESC mejoró los cambios patológicos, promoviendo la remielinización.

Does neuroectodermal stem cells transplantation restore neural regeneration and locomotor functions in compressed spinal cord injury rat model? / ¿El trasplante de células madre neuroectodérmicas restaura la regeneración neural y las funciones locomotoras en el modelo de rata con lesión de la médula espinal comprimida?

SUMMARY: The aim of this study was to determine the possible regenerative effect of neuroectodermal stem cells on the ultrastructural, and locomotor function resulting from compressed injury to the spinal cord in a rat model. Forty male rats were divided into control and sham groups (20 rats each). Compressed spinal cord injured (CSCI) were forty rats which subdivided equally into: untreated, treated by neuroectodermal stem cells (NESCs). After four weeks, all rats in different groups were scarified, samples were taken from central, cranial, and caudal to the site of spinal cord injury. Specimens were prepared for light and electron microscopic examination. The number of remyelinated axons in central, cranial and caudal regions to the injured spinal cord after transplantation of NESCs was counted. The open field test assessed the locomotor function. Results revealed that compressed spinal cord injury resulted in loss and degeneration of numerous nerve fibers, myelin splitting and degeneration of mitochondria. Four weeks after transplantation of NESCs regenerated axons were noticed in cranial and central sites, while degenerate axons were noticed caudal to the lesion. Number of remyelinated axons was significantly increased in both central and cranial to the site of spinal cord injury in comparison with caudal region which had the least number of remyelinated axons. Transplantation of NESCs improved significantly the locomotor functional activity In conclusion, neuroectodermal stem cells transplantation ameliorated the histopathological and ultrastructural changes, and improved the functional locomotor activity in CSCI rat.

RESUMEN: El objetivo de este estudio fue determinar el posible efecto regenerativo de las células madre neuroectodérmicas en la función ultraestructural y locomotora de una lesión comprimida en la médula espinal en un modelo de rata. Cuarenta ratas macho se dividieron en grupos control y sham (20 ratas en cada grupo). La médula espinal lesionada (CSCI) tenía cuarenta ratas que se subdividieron de igual forma en los siguientes grupos: no tratadas, tratadas con células madre neuroectodérmicas (NESCs). Al término de cuatro semanas, todas las ratas en los diferentes grupos fueron escarificadas, se tomaron muestras de las áreas central, craneal y caudal en relación al sitio de la lesión de la médula espinal. Las muestras fueron preparadas para examen microscópico de luz y electrónica. Se contó el número de axones remielinizados en las regiones central, craneal y caudal de la médula espinal lesionada después del trasplante de NESCs. La prueba de campo abierto evaluó la función locomotora. Los resultados revelaron que la lesión de la médula espinal comprimida provocó la pérdida y degeneración de numerosas fibras nerviosas, la división de la mielina y la degeneración de las mitocondrias. Cuatro semanas después del trasplante de NESCs, se notaron axones regenerados en los sitios craneales y centrales, mientras que los axones degenerados se notaron caudal a la lesión. El número de axones remielinizados aumentó significativamente tanto en el centro como en el cráneo hasta el sitio de la lesión de la médula espinal en comparación con la región caudal que tenía el menor número de axones remielinizados. El trasplante de NESCs mejoró significativamente la actividad funcional locomotora. En conclusión, el trasplante de células madre neuroectodérmicas mejoró los cambios histopatológicos y ultraestructurales, y mejoró la actividad locomotora funcional en la rata CSCI.

Detection of a Usp-like gene in Calotropis procera plant from the de novo assembled genome contigs of the high-throughput sequencing dataset.

The wild plant species Calotropis procera (C. procera) has many potential applications and beneficial uses in medicine, industry and ornamental field. It also represents an excellent source of genes for drought and salt tolerance. Genes encoding proteins that contain the conserved universal stress protein (USP) domain are known to provide organisms like bacteria, archaea, fungi, protozoa and plants with the ability to respond to a plethora of environmental stresses. However, information on the possible occurrence of Usp in C. procera is not available. In this study, we uncovered and characterized a one-class A Usp-like (UspA-like, NCBI accession No. KC954274) gene in this medicinal plant from the de novo assembled genome contigs of the high-throughput sequencing dataset. A number of GenBank accessions for Usp sequences were blasted with the recovered de novo assembled contigs. Homology modelling of the deduced amino acids (NCBI accession No. AGT02387) was further carried out using Swiss-Model, accessible via the EXPASY. Superimposition of C. procera USPA-like full sequence model on Thermus thermophilus USP UniProt protein (PDB accession No. Q5SJV7) was constructed using RasMol and Deep-View programs. The functional domains of the novel USPA-like amino acids sequence were identified from the NCBI conserved domain database (CDD) that provide insights into sequence structure/function relationships, as well as domain models imported from a number of external source databases (Pfam, SMART, COG, PRK, TIGRFAM).

Effect of maternal low protein diet during pregnancy on the fetal liver of rats.

Maternal protein restriction plays a critical role in the developmental programming of later disease susceptibility of the fetus. Developmental insults could exert permanent effects on health through alteration of tissue morphology. As the liver has the greatest number of functions among other body organs, this study aimed at evaluating the effects of maternal dietary protein insufficiency on the structure and the proliferative capacity of the liver in rat fetuses. Morphometric histological studies and biochemical analysis were performed. Twenty adult Albino female Wistar rats were divided into two groups after confirmation of pregnancy. Group I (ST), serving as control, was fed a standard diet (20% protein) and group II (LP) a low protein diet (5% protein). Fetuses were extracted on the day 21.5 of pregnancy. Group II morphometric results revealed a significant decrease in the mothers' weight gain, number and weight of fetuses and weight of fetal livers, but there was also an increase in the mean area of hepatocytes. Histological results showed apoptosis, vacuolization of the hepatocytes, increased positivity of the Oil Red O stained fat droplets and the PAS-positive stained glycogen granules. Liver TUNEL showed increased apoptotic nuclei. Ki-67 immunostaining showed decreased proliferation of the hepatocytes. Ultrastructurally, the nucleus showed peripheral masses of heterochromatin besides irregular nuclear and cell membranes. Mitochondria varied in shape with loss of cristea. Biochemically, there was a significant decrease in the protein concentration and a significant increase in the glycogen concentration in livers of group II. It thus appears that the maternal metabolic condition not only reduced fetal growth in response to protein restriction, but also altered the structure of the liver.