The relation between autophagy modulation by intermittent fasting and aquaporin 2 expression in experimentally induced diabetic nephropathy in albino rat.

Polyuria is an early sign of diabetic nephropathy (DN) that produces dehydration in diabetic patients. This could be caused by alteration of renal aquaporin 2 (AQP2) expression. This study aimed to describe the relation between autophagy modulation via intermittent fasting (IF) and renal AQP2 expression and polyuria in case of DN. We divided the rats into control, DN and IF groups. After 2 and 4 weeks of diabetes induction, blood glucose (BG), serum creatinine (Scr), urine volume, and 24 hours urine protein (UP) were examined. Diabetic nephropathy histopathological index (DNHI) was calculated to evaluate histopathological changes. Immunohistochemistry and real-time PCR were performed to measure the levels of AQP2 and the autophagy marker; LC3 in kidney tissue. DNHI was correlated to the PCR and immunoexpression of AQP2 and LC3. Intermittent fasting significantly decreased the BG, Scr, urine volume, 24 hours UP, and DNHI as compared diabetes. Diabetes significantly elevated the immunoreactivity and mRNA expression levels of AQP2 and LC3 as compared to the control. However, the IF decreased AQP2 and stimulated autophagy in cyclic fashion. Our data revealed significant positive correlations between AQP2 and LC3 at the level of immunoexpression and mRNA at 2nd weeks. Taken together, these data showed that autophagy stimulation didn't regulate AQP2 expression in case of diabetic nephropathy, however IF decreased polyuria through improvement of glycemic state.

Effect of voluntary running on expression of myokines in brains of rats with depression.

This study aimed to demonstrate the histopathology and immunoexpression of exercise-derived myokines in dentate gyrus (DG), medial prefrontal cortex (mPFC) and cerebellum of depressed Wistar rats during depression and after practising voluntary running. Depression was developed by forced swimming for 2 weeks. Voluntary running was performed by voluntary running for 3 weeks. Brain sections were processed and immunostained to detect brain-derived neurotrophic factor (BDNF), macrophage migration inhibitory factor (MIF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). ImageJ software was used to measure the optical density (OD). BDNF was expressed in neurons in DG, mPFC and granular and Purkinje cells in cerebellum. MIF was expressed in neurons of sub-granular zone in DG, mPFC and Purkinje cells. VEGF was expressed in many neurons in DG, mPFC and Purkinje cells. IL-6 was expressed in some neurons in DG, in neuropil of mPFC and in Purkinje cells. In depression, the OD of studied myokines significantly decreased in all examined areas. After voluntary running, the OD of myokines significantly increased in all areas. This study defines the immunohistochemical expression of myokines in brain areas in depression and after voluntary running and reveals the involvement of the mPFC and cerebellum in the pathophysiology of depression.

Regeneration of the Fallopian Tube Mucosa Using Bone Marrow Mesenchymal Stem Cell Transplantation After Induced Chemical Injury in a Rat Model.

In this study, we describe a novel insight about the use of bone marrow-derived mesenchymal stem cells (BM-MSCs) for fallopian tube (FT) regeneration. Seventy rats' tubes were involved in this study and divided into 4 groups: control (15), ethanol injured (20), mesenchymal stem cell (MSC)-recipient without injury (15), and MSC recipient after injury (20). The BM-MSCs were isolated from male rats, and their incorporation into the tissues was confirmed by the detection of Sry gene in MSC-recipient rats using RT-PCR. Histological and immunohistological sections of the 4 groups were comparably evaluated. We found that direct injection of ethanol into FT caused structural impairment, which was restored largely after receiving MSCs. We have revealed for the first time that prominin 1 (Prom1, stem cell marker) was expressed in the fimbriated distal tubal end. The MSC transplantation caused (1) significant increase in the tissue level and immunoexpresstion of Prom1 ( P < .001 and P = .017, respectively) and vascular endothelial growth factor (VEGF; vasculogenic marker; P < .001 and P = .004, respectively), (2) significant increase in the immunoexpresstion of proliferating cell nuclear antigen (PCNA; proliferation marker; P < .001), and (3) significant decrease in the immunoexpresstion of caspase 3 (CASP-3; apoptotic marker; P < .001) compared to the injured tissues. In conclusion, MSCs could exhibit its restorative effect on FT through their ability to (1) activate the resident stem cells in the distal tubal end, (2) mediate the expression of VEGF and PCNA, and (3) influence tissue apoptosis. This study laid the foundation for assessing the contribution of stem cells in the distal tubal end in direct repair of the tube when required to assist reproduction.

Hyperglycemia Alters the Protein Levels of Prominin-1 and VEGFA in the Retina of Albino Rats.

In this study, we addressed the potential relationship between prominin-1 (prom1) and vascular endothelial growth factor (VEGFA) in diabetes-induced retinopathy. In total, we examined 28 retinas from 14 rats with streptozotocin-induced diabetes and 30 retinas from 15 untreated control rats. ELISA was used to measure the level of prom1 and VEGFA in retinal tissue homogenates. Immunohistochemical techniques were used with antibodies directed against prom1, VEGFA, and CASP-3. After 180 days of diabetes induction, we performed light and electron microscopy studies on rat eyes to evaluate histopathological changes and to estimate the de novo metric "Diabetic Retinopathy Histopathological Index" (DRHI). These changes were then correlated to the tissue and immunoexpression levels of prom1 and VEGFA. The data showed a significant upregulation of the tissue levels and optical densities (ODs) of VEGFA and prom1 immunoreactivity in diabetic retinas compared with controls. Both the tissue levels and OD values of prom1 and VEGFA correlated significantly with each other and to the diabetic structural changes as calculated by DRHI. Taken together, these data provide new insight into the potential role of prom1 and VEGFA in the development of diabetic retinopathy.

Structural evaluation of the peritubular sheath of rat's testes after administration of ribavirin: A possible impact on the testicular function.

Effects of ribavirin on the structure of peritubular sheath (PS) of seminiferous tubules and on testicular functions were studied. We found that ribavirin at a dose of 4 mg/kg/day for 4 weeks produced a significant reduction in testosterone level (6.3 ± 0.2; P < 0.001) and in spermatogenic score count (3.8 ± 0.2; P < 0.001) compared to control values. The thickness of PS (17.8 ± 1.13) and tubular lumen perimeter (1024.7 ± 67) was significantly increased compared to controls (10.7 ± 0.70; P < 0.001 and 808 ± 25; P = 0.004, respectively). The length of germinal epithelium (411.8 ± 39) and tubular external diameters (1661.8 ± 115) was significantly reduced compared to control values (708.4 ± 40; P < 0.001 and 2358.8 ± 169; P < 0.001, respectively). The basement membranes (BMs) were thickened with great deposition of collagen. Myoid cells showed altered structure and extracellular matrix revealed disorganization by excessive collagen I and IV accumulation. Testicular damage was established histologically. Evidence of apoptosis was detected in germ cells. There was a significant increase in integrated density of Casp-3 expression (38,121,743 ± 1,763,420; P < 0.001) in seminiferous tubules compared to control (24,788,409 ± 1,900,140). It is concluded that ribavirin can cause alterations of the testicular function and structure with increased apoptosis in the tissues after 4 weeks of administration. The damaging effect could be persuaded by destruction of the peritubular sheath.

Voluntary running improves depressive behaviours and the structure of the hippocampus in rats: A possible impact of myokines.

This study investigated the impact of voluntary exercise on depressive behaviours, serum and hippocampal levels of myokines, and histopathological features of hippocampal formation in rats. Depressed rats were allowed to voluntarily run on a wheel for 3weeks. Locomotor activity was assessed by a forced swimming test and the myokine levels in sera and hippocampal homogenates were measured using Enzyme-linked Immunosorbent Assay. Brain sections were analysed for hippocampal structure and neuronal counts. Voluntary running produced significant increase in the distance moved by rats and significant decrease in immobility duration. After voluntary running, there were significant increases in serum and hippocampal brain-derived neurotrophic factor (BDNF) and macrophage migration inhibitory factor (MIF), significant increase in hippocampal vascular endothelial growth factor (VEGF), and significant decrease in serum interleukin-6 (IL-6). Significant correlation was detected between the serum levels of BDNF and MIF (r=0.276) as well as IL-6 (r=-0.340). In addition, significant correlation was observed between hippocampal BDNF levels and MIF (r=0.500) and VEGF levels (r=0.279). After voluntary running, there was significant decrease in number degenerated neurons in hippocampal areas and significant increase in number of healthy neurons in the upper limb of the dentate gyrus, but not in its lower limb, compared to depression group. This study showed the relation of myokines to the development and/or relief of depression, as well as the correlation between serum and hippocampal myokine levels. Attention should be paid to studying the biological effects of myokines on different hippocampal areas that could respond differently to treatments.

Ultrastructure and histomorphometric analysis of human umbilical cord vessels in preeclampsia: a potential role of VEGF, VEGFR-1 and VEGFR-2.

AIM: This study aimed to analyze the ultrastructure and histomorphometric changes of the human umbilical cord vessels of preeclampsia compared to healthy pregnancies and the possible role of vascular endothelial growth factor (VEGF) and its receptors. MATERIALS AND METHODS: Umbilical cord (UC) specimens were collected between August, 2014 and July, 2015. Histomorphometric analysis of UC vessels was performed utilizing an image analysis system. Cellular localization of VEGF, VEGFR-1 (VEGF receptor-1) and VEGFR-2 (VEGF receptor-2) were examined in immunohistochemically-stained sections of UC from 45 pregnancies with preeclampsia (PE) and 40 healthy pregnancies. RESULTS: Compared with healthy pregnancies, UC venous measurements were significantly higher in PE; total venous area (p<0.001), luminal venous area (p<0.001) and luminal venous index (p=0.005). Arterial measurements except for the total arterial area were significantly lower in the PE compared to healthy pregnancies, luminal arterial area (p=0.32) and luminal arterial index (p=0.004). Histological and ultrastructural examination of UC from PE revealed discontinuity of vascular endothelium and disorganized edematous widely spaced smooth muscle cells. We demonstrated a significant increase in tissue expression of VEGF in PE (16.6±0.1) compared to healthy pregnancies (12±0.8) (p=0.001). Also, significant higher VEGFR-1 expression in PE (20.5±2.5) compared to healthy pregnancies (9.5±1.2) (p<0.001) has been observed. However, tissue expression of VEGFR-2 was decreased significantly in PE (10.5±0.7) compared to healthy pregnancies (13.8±1.6) (p=0.043). CONCLUSIONS: Altered tissue expression of VEGF and its receptors in the UC vessels could play a crucial role in disturbing the UC vascular endothelium, smooth muscles and measurements and this may underlie the existence of preeclampsia.

Human umbilical cord blood-mesenchymal stem cells transplantation renovates the ovarian surface epithelium in a rat model of premature ovarian failure: Possible direct and indirect effects.

This study aimed to isolate mesenchymal stem cells (MSC) from human umbilical cord blood (HCB) and to explore their influence on the ovarian epithelium after paclitaxel-induced ovarian failure. Ninety-five rats were divided into 6 groups: control, paclitaxel, paclitaxel and saline, HCB-MSC-treated for 2 weeks, HCB-MSC-treated for 4 weeks, and HCB-MSC-treated for 6 weeks. HCB cells were studied for CD34, CD44, and Oct ¾ using flow cytometry. Serum levels of FSH and E2 were measured using ELISA, RT-PCR analysis for human gene; beta-actin (ACTB), immunohistochemical analysis for CK 8/18, TGF-ß, PCNA and CASP-3 were performed. We found that ACTB gene was expressed in all rats' ovaries received HCB-MSC. After 4 weeks of transplantation, there was significant reduction in FSH, elevation in E2 levels, stabilization of the surface epithelium morphostasis, an increase in the antral follicle count and increase in integrated densities (ID) of CK 8/18, TGF-ß, and PCNA expressions and decrease in ID of CASP-3 expression. We concluded that HCB-MSC can restore the ovarian function after paclitaxel injection through a direct triggering effect on the ovarian epithelium and/or indirect enrichment of ovarian niche through regulating tissue expression of CK 8/18, TGF-ß and PCNA. These molecules are crucial in regulating folliculogenesis and suppressing CASP-3-induced apoptosis.

Enhanced expression of vascular endothelial growth factor and increased microvascular density in women with endometrial hyperplasia: a possible relationship with uterine natural killer cells.

This case-control study aimed to investigate the expression of natural killer cells (NKCs) and the integrated optical density (IOD) of vascular endothelial growth factor (VEGF) and to quantify microvascular density (MVD) in endometrial biopsies from women with endometrial hyperplasia (EH) relative to normal subjects. Histological data from four groups were analyzed. The study population included 30 women with simple EH without atypia, 25 patients with complex EH without atypia, 25 with complex EH with atypia and 25 healthy women with non-hyperplastic endometrium (control group). Paraffin sections were immunostained with antibodies against CD56, VEGF-A and CD34 using an Avidin-Biotin-Peroxidase technique. The evaluation of NKC density and IOD of VEGF expression and measurement of MVD were performed using light microscopy examination and image analysis techniques. Increased numbers of NKCs were documented in cases of complex EH with atypia compared with the other groups (p<0.001). The number of NKCs was lower in cases of hyperplasia without atypia compared with the controls, but the difference was not significant. The IOD of VEGF-A and MVD increased significantly with progression from the non-hyperplastic endometrium through the three groups of EH (p<0.001). We observed a significant correlation between the MVD and the IOD of VEGF-A in the studied groups (r=0.434; p<0.001). Additionally, NKCs density was correlated significantly with IOD of VEGF-A (r=0.661; p<0.001) and with the MVD (r=0.473; p<0.001). These results suggest that NKC-count, IOD of VEGF and endometrial MVD are all related to the histological changes of the endometrium and that endometrial hyperplasia exhibits distinct immunological backgrounds in the context of NKC infiltration and VEGF production.

Ultrastructure alteration of decidual natural killer cells in women with unexplained recurrent miscarriage: a possible association with impaired decidual vascular remodelling.

This study aimed to evaluate the extent of remodelling of intra-decidual segments of the spiral arteries in human deciduas between the 6th and 10th gestational weeks in women with unexplained recurrent miscarriages (RM) in comparison to gestational-matched controls. A possible association with the number, immunoexpressive behaviour and ultrastructural changes of decidual natural killer cells (dNKCs) was investigated. Decidual biopsies were obtained from RM cases (n = 40) and women with no history of spontaneous miscarriage and at least one live birth at term (n = 30). Staining was performed using PAS, anti-CD34 and anti-CD56 antibodies, using an avidin-biotin-peroxides technique. Analysis by means of light and transmission electron microscopy was employed. To determine the extent of remodelling of decidual vessels, a quantitative score was analysed using histological criteria of vascular transformation and then related to the number of CD56(+) dNKCs. In RM, dNKCs were distributed among decidual cells and around the vessels. They possessed numerous polyploidic protrusions on cell membranes crossing from one cell to another. The cells became more irregular and exhibited heterogeneous electron-dense granules in their cytoplasm compared to controls. The non-remodelling score and number of dNKCs were significantly increased in RM group (p < 0.001). The number of dNKCs was significantly correlated with the scores in both control (r = 0.491; p = 0.006) and RM (r = 0.852; p < 0.001) groups. It appears that dNKCs play a key role in impaired decidual artery remodelling that may be involved with early RM. This may be due to increased numbers of cells or impaired cellular interactions resulting from alterations to the ultrastructure.

Platelet rich plasma enhances the immunohistochemical expression of platelet derived growth factor and vascular endothelial growth factor in the synovium of the meniscectomized rat models of osteoarthritis.

This study was carried out on a rat model of surgically-induced osteoarthritis (OA) to assess the histological and immunohistochemical changes in the synovial membrane and to evaluate the effects of intra-articular injection of platelet rich plasma (PRP) in such cases. Forty five male albino rats were divided into 3 equal groups; control, surgically-induced OA and surgically-induced OA followed by intra-articular injection of PRP. Knee joints were processed for histological and immunohistochemical staining with anti-platelet derived growth factor (PDGF-A) and anti-vascular endothelial growth factor (VEGF) and the area percentages of immunostaining were measured by digital image analysis. Serum levels of PDGF-A and VEGF were analyzed by ELISA. The osteoarthritis research society international (OARSI) score was significantly higher in OA (2433.8±254) than in control (230.4±37.8; p<0.001) and in PRP-treated tissues (759.7±45.8; p<0.001). The immunostained area percentages for PDGF-A was significantly higher in PRP-treated tissues (20.6±2.4) than in OA (11.06±1.3; p=0.007) and in control tissues (4.1±0.78; p<0.001). Likewise, the immunostained area percentage for VEGF was significantly higher in PRP-treated tissues (22.5±1.6) than in OA (14.9±1; p=0. 002) and in control tissues (6.5±0.7; p<0.001). ELISA analysis revealed a significant increase in serum levels of the PDGF-A and VEGF after intraarticular PRP injection when compared to the other groups (p<0.000). The present study concluded that intra-articular injection of PRP could produce optimizing effects in surgically induced OA in the form of; decreasing the OARSI score, improving the inflammatory events in synovium and modulating the PDGF-A and VEGF serum levels and synovial tissue immunoexpression. These effects could be reflected positively on the associated chondral defect.

Effects of a single course versus repeated courses of antenatal corticosteroids on fetal growth, placental morphometry and the differential regulation of vascular endothelial growth factor.

AIM: To investigate the impact of antenatal exposure to a single course or repeated courses of dexamethasone (DEX) on neonatal anthropometrics, placental morphometry and potential effect on maternal plasma levels and placental expression of vascular endothelial growth factor (VEGF). METHODS: Pregnant women between 27 and 32 weeks of gestation who delivered between 28 and 40 weeks and received a single course (n = 38) or repeated courses (n = 33) of DEX were compared to gestational age-matched controls (n = 30). Maternal blood samples were obtained, and placental biopsy was taken. Area percent of VEGF immunostaining and villous capillarization index were evaluated using image analysis. RESULTS: Infants exposed to repeated courses of DEX were significantly associated with decreased birthweight, body length, head circumference and placental weight compared with controls (P = 0.011, P < 0.001, P = 0.004, P < 0.001, respectively) and with the group that received a single course of DEX (P = 0.021, P = 0.020, P = 0.049, P = 0.010, respectively). There was a significant decrease in maternal VEGF plasma levels and percentage of VEGF immunostained area after repeated courses of DEX compared with controls (P < 0.001 and P = 0.001, respectively) or a single course (P = 0.028 and P = 0.002, respectively). Notably, repeated courses of DEX impaired normal increase in villous capillarization index compared with controls or a single course (P = 0.001 and P = 0.041, respectively). CONCLUSION: Repeated antenatal courses of DEX compromised fetal and placental growth compared with a single course of DEX, and these effects were potentially mediated by altered maternal plasma levels and placental expression of VEGF with consequent decrease in placental vascularization. Because of continuing uncertainties, several key messages for clinicians are provided.

Expression of tumor necrosis factor-alpha and vascular endothelial growth factor in different zones of fetal membranes: a possible relation to onset of labor.

This study aimed to explore whether the altered expression of tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF) and apoptotic changes in mid zone (MZ) and rupture zone (RZ) of fetal membranes (FM) are regulatory mechanisms associated with labor at term. Fifteen FM specimens were collected after vaginal deliveries and 13 specimens after elective caesarian section. Histological and immunohistochemical analysis were employed. Area percent of TNF-α and VEGF immunostaining and apoptotic index (AI) were evaluated using image analysis. The statistical data revealed significantly higher area % for TNF-α, VEGF immunoexpression and AI in labor compared to non-labor specimens (p < 0.0001). There was a significantly higher percentage of TNF-α immunoexpressed area in MZ compared with RZ in both groups (p < 0.0001). VEGF expression in RZ of both groups proved nearly double or triple the area % of expression relative to MZ with highly significant difference (p < 0.0001). quantitative analysis revealed near two fold increase in the AI in RZ (13.42% ± 1.2 in labor; 11.20% ± 0.96 in non-labor groups) when compared to MZ (7.20% ± 0.6 in labor; 5.08% ± 0.76 in non-labor groups) with highly significant zonal difference (p < 0.0001). Correlation analysis revealed significant correlation between apoptotic indices and area % of TNF-α (r = 0.575, p = 0.002 in non-labor; r = 0.652, p < 0.0001 in labor) and VEGF (r = 0.795, p < 0.0001 in non-labor; r = 0.668, p < 0.0001 in labor). In conclusion, Apoptosis may be regulated by TNF-α and VEGF expression in FM at labor. MZ is a step back from RZ and could participate actively in rupture of the FM during labor. TNF-α and VEGF increase with onset of labor and differentially expressed in the RZ and the MZ. These findings call for further study with tissue cultures or animal models.

Histomorphological evaluation of maternal and neonatal distal airspaces after maternal intake of nanoparticulate titanium dioxide: an experimental study in Wistar rats.

This study was performed to determine the histomorphological alterations occurring in maternal and neonatal pulmonary distal airspaces of Wistar rats after maternal administration of titanium dioxide nanoparticles (TiO2 NPs). Thirty adult pregnant rats (150-250 g) and their offspring were used in this study. Pregnant rats were randomly divided into control (n = 15) and TiO2 NP-treated (n = 15) groups. A suspension of TiO2 NPs in phosphate-buffered saline was given orally to the treated group (0.1 ml/10 g body weight once daily) from days 6 to 12 of gestation. At term, maternal and neonatal lungs were collected and processed for energy-dispersive X-ray (EDX) and histological analysis. The mean linear intercept (MLI) and airspace wall thickness were measured by a stereological procedure with image analysis to assess alveolarization. EDX analysis demonstrated the presence of TiO2 in maternal and neonatal lungs. The lungs of TiO2 NP-treated mothers revealed evidence of pneumocytic apoptosis, abnormal lamellar inclusions, and macrophage and inflammatory cell infiltrates. Significant thinning of alveolar septa was detected in the treated rats (p < 0.001), but the MLI was constant in both groups (p = 0.207). Neonatal lungs from treated mothers revealed deficient septation, thickened mesenchyme between the saccules, pneumocytic apoptosis, atypical lamellar inclusions, and macrophage infiltration. The thickness of the primary septa was significantly increased (p = 0.001) with no significant change in MLI (p = 0.579) compared with the control group. In conclusion, TiO2 NPs were detected in maternal and neonatal lungs after oral intake by pregnant rats. The pulmonary response manifested as inflammatory lesions and delayed saccular development in neonates.

Placental growth factor and soluble Fms-like tyrosine kinase 1 in diabetic pregnancy: A possible relation to distal villous immaturity.

This study aimed to describe the prevalence of chorionic distal villous immaturity (DVI) in overt diabetic/gestational diabetic (OD/GD) women compared with normoglycemic ones and to analyze the relation of DVI index (DVII) to placental growth factor (PlGF) and soluble Fms-like tyrosine kinase 1 (sFlt-1). Three groups were studied; normoglycemics (n=21), OD (n=17) and GD (n=20). Maternal blood samples were evaluated regarding serum levels of PlGF and sFlt-1. Immunohistochemical methodologies were employed in term placentae of all subjects to assess DVII and area% of PlGF and sFlt-1 immunostaining. We found that mean Hemoglobin A1c (HbA1c) is 5.22±0.15 in normoglycemics, 6.2±0.3 in OD, and 5.70±0.23 in GD with significant differences between groups (p=0.012). DVII was significantly higher in OD (66.6±4.7) and GD (72.4±4.5) compared to controls (11.6±2.5; p=0.000). Healthy women have significantly lower levels of PlGF (86.6±14.5) compared to OD (166.6±22.4, p=0.000) and GD (150.3±23.97, p=0.000) and their placentae expressed a significantly lower area% of PlGF (6.5±0.8) compared to OD (14.8±1.0, p=0.000) and GD (18.8±1.3, p=0.000). Also, normoglycemic women have significantly lower levels of sFlt-1 (108.9±12.1) compared to OD (226.5±18.6, p=0.000) or GD (197.2±16.8, p=0.000) and their placentae expressed a significantly lower area% of sFlt-1 (3.2±0.3) compared to OD (15.4±1.7, p=0.000) and GD (16.9±1.2, p=0.000). There was significant correlation between DVII and both serum level and area% of PlGF and sFlt-1 expression in the 3 groups. This study provided a new score for evaluating DVI in normal and diabetic placentae and suggested a role for PlGF and sFlt-1 in regulation of DVI in diabetic pregnancies.

Morphometric analysis of terminal villi and gross morphological changes in the placentae of term idiopathic intrauterine growth restriction.

The aim of this study is to compare the gross morphology of the placentae and the morphometry of terminal villi and terminal villous capillaries in pregnancies complicated by idiopathic intrauterine growth restriction (IUGR) with those of normal pregnancies. 75 placentae were collected between April 2010 and March 2011. 50 placentae were associated with idiopathic IUGR and 25 were from controls. Insertion of cords, placental weights and diameters were noted. Hematoxylin and eosin-stained wax sections were analyzed stereologically. Growth of terminal villi and fetal capillaries was assessed by estimating total and mean surface areas. Villous capillarization was monitored using capillary:villus surface ratio. Measurements were done using image analysis system. In comparison with the control group, idiopathic IUGR placentae are significantly smaller (p=0.000) and lighter (p=0.000). In majority of IUGR (68%) and control (60%) cases, eccentric insertion of cord is noted. In idiopathic IUGR group, there is a significant decrease in the total areas of both terminal villi (p=0.048) and their capillaries (p=0.000) and a significant decrease in number of both terminal villi (p=0.000) and their capillaries (p=0.001), also, capillarization index is significantly smaller (p=0.038). Idiopathic IUGR is associated with reduced growth of placental terminal villi and fetal capillaries and this is accompanied by changes in measures of villous capillarization as compared with those of control placentae. Further investigations of idiopathic IUGR placentae are necessary, especially considering the histopathological changes that could affect the fetomaternal exchange, with a note that strict distinction should be made between idiopathic and nonidiopathic IUGR placentae.

Structural analysis of human placental stem and terminal villi from normal and idiopathic growth restricted pregnancies.

Studying in detail different histomorphological and pathological findings in placental stem and terminal villi of appropriate for gestational age (AGA) and idiopathic intrauterine growth restricted (IUGR) fetuses, then analyzing their correlation to the neonatal birth weight and to the some morphological features of the placenta. Fifty full-term human placentae of idiopathic IUGR and 25 of AGA pregnancies were processed for haematoxylin and eosin staining and evaluated by light microscope aided with Image Analyzer. The mean number of stem villous arteries, and the mean number of terminal villous capillaries per field are significantly lower in idiopathic IUGR group (4.63 ± 0.46, 47.09 ± 4.44, respectively) than in AGA group (12.36 ± 0.61, 73.35 ± 5.13, respectively) (p = 0.001). Both AGA and idiopathic IUGR placentae share the presence of many pathological features: (1) narrowing of stem villous arteries appears in 38 (76 %) of IUGR cases and in 9 (36 %) of AGA cases with significant difference between groups (p = 0.001); (2) cellular infiltration (villitis) of the stem villi is significantly higher in IUGR cases [24 (48 %)] than in AGA cases [2 (8 %)] (p = 0.001). The study shows significant correlation between the birth weight and different pathologic features in the stem villi as arterial number (r = 0.494; p = 0.000), arterial narrowing (r = 0.283, p = 0.004), degenerative changes (r = 0.331, p = 0.001) and villitis (r = 0.275, p = 0.005). There is also significant correlation between neonatal birth weight and terminal villous capillary number (r = 0.281, p = 0.001) but no significant correlation is found between the birth weight and terminal villous fibrotic changes (r = -0.098, p = 0.318). Histomorphological and pathological changes in the stem villi could explore the cause of idiopathic IUGR. Stem villous arterial number, arterial narrowing, degeneration and villitis could be underlying mechanisms. Further researches on the hormonal and cytokine level should be undertaken to demonstrate the precipitating factors of these changes and the possible preventing measures.

Expression pattern of tumor necrosis factor alpha in placentae of idiopathic fetal growth restriction.

Tumor Necrosis Factor-Alpha (TNF-α) is one of the proinflammatory cytokines that provokes a variety of biological effects on the placenta. The increased placental exposure to TNF-α have induced impaired fetal development in experimental animals, but no data are available on the expression and localization of TNF-α in human placenta of idiopathic fetal growth restriction (FGR). The aim of this study was to characterize the immunohistochemical expression and localization of TNF-α in idiopathic FGR placentae in comparison with those of appropriate for gestational age (AGA) fetuses. 75 human placentae were collected between April, 2010 and March, 2011; 50 placentae were collected from pregnancies associated with idiopathic FGR and 25 placentae from AGA pregnancies. Histological and Immunohistochemical methodologies were employed in formalin fixed paraffin-embedded sections from the placentae of all subjects. Area percent of TNF-α immunostaining was evaluated using image analysis technique. In both AGA and idiopathic FGR placentae, cytoplasmic TNF-α was localized in the decidual and chorionic trophoblasts and in the endothelium of decidual and chorionic vessels. Trophoblast giant cells (TGC) in the decidua and chorionic villi of AGA specimens show deficient or negative TNF-α immunoexpression while those of idiopathic FGR show positive immunostaining. The mean area percent of TNF-α staining was greater in idiopathic FGR placentae (5.93 ± 0.69) compared to AGA ones (3.28 ± 0.41) (p = 0.001). Enhanced placental expression and specific cellular localization and of TNF-α are expected to contribute to impaired fetal development in idiopathic FGR and the TGCs are proposed to be an obvious source of this cytokine in such cases.

Index to ring digit ratio in Saudi Arabia at Almadinah Almonawarah province: a direct and indirect measurement study.

The digit ratio, or the relative lengths, of the 2nd and 4th digits (2D :4D) shows a sex difference, with males tending to have lower values in comparison with females. This sex differences arises early in the fetus and may result from the effects of prenatal testosterone and estrogen on the relative growth rate of the 2nd and 4th digits. This study aimed to estimate finger lengths and the 2D:4D ratios for the first time in Saudi Arabian subjects using direct and indirect measurements, and to evaluate the correlations between both indirect and direct 2D:4D with adult testosterone and various sexually dimorphic physical traits. The results revealed the following: (i) mean 2D:4D in Saudi Arabian samples varied from 0.96 to 0.99; (ii) mean 2D:4D was lower for indirect compared to direct 2D:4D; (iii) sex differences in indirect 2D:4D were higher than in direct 2D:4D measurements; (iv) there were no significant correlations between indirect or direct 2D:4D and testosterone level; (v) there were four significant correlations between direct 2D:4D and body size traits but no significant correlations between indirect 2D:4D and body size.