The effect of maternal separation stress-induced depression on ovarian reserve in Sprague Dawley Rats: The possible role of imipramine and agmatine through a mTOR signal pathway.

PURPOSE: To examine the possible role of impramine and agmatine through a mTOR signal pathway on rat ovary after maternal separation stress-induced depression. METHODS: Sprague Dawley neonatal female rats were divided into control, maternal separation (MS), MS+imipramine, and MS+agmatine groups. Rats were subjected to MS for 4 hours daily from postnatal day (PND) 2 to PND 21 and pups were exposed to social isolation (SI) on PND23 for 37 days for model establishment treated with imipramine (30 mg/kg; ip) or agmatine (40 mg/kg; ip) for 15 days. In order to examine behavioral changes rats were all subjected to locomotor activity and forced swimming tests (FST). Ovaries were isolated for morphological evaluation, follicle counting and mTOR signal pathway protein expression levels were detected. RESULTS: Increased number of primordial follicles and diminished ovarian reserve in the MS groups were detected. Imipramine treatment caused diminished ovarian reserve and atretic follicle; however, agmatine treatment provided the maintenance of ovarian follicular reserve after MS. mTOR signal pathway may have an important role during rat ovarian follicular development in model of MS. CONCLUSIONS: Our findings suggest that agmatine may help to protect ovarian reserve during follicular development by controlling cell growth.

Overview of junctional complexes during mammalian early embryonic development.

Cell-cell junctions form strong intercellular connections and mediate communication between blastomeres during preimplantation embryonic development and thus are crucial for cell integrity, polarity, cell fate specification and morphogenesis. Together with cell adhesion molecules and cytoskeletal elements, intercellular junctions orchestrate mechanotransduction, morphokinetics and signaling networks during the development of early embryos. This review focuses on the structure, organization, function and expressional pattern of the cell-cell junction complexes during early embryonic development. Understanding the importance of dynamic junction formation and maturation processes will shed light on the molecular mechanism behind developmental abnormalities of early embryos during the preimplantation period.

Circadian regulation of mTORC1 signaling via Per2 dependent mechanism disrupts folliculogenesis and oocyte maturation in female mice.

mTOR (mammalian target of Rapamycin) is an important signaling pathway involved in several crucial ovarian functions including folliculogenesis and oocyte maturation. The circadian rhythm regulates multiple physiological processes and PER2 is one of the core circadian rhythm components. mTOR is regulated by the circadian clock and in turn, the rhythmic mTOR activities strengthen the clock function. Our current study aims to investigate a possible interconnection between the circadian clock and the mTORC1 signaling pathway in folliculogenesis and oocyte maturation. Here we demonstrate that the circadian system regulates mTORC1 signaling via Per2 dependent mechanism in the mouse ovary. To investigate the effect of constant light on ovarian and oocyte morphology, animals were housed 12:12 h L:D group in standard lightening conditions and the 12:12 h L:L group in constant light for one week. Food intake and body weight changes were measured. Ovarian morphology, follicle counting, and oocyte aging were evaluated. Afterward, western blot for mTOR, p-mTOR, p70S6K, p-p70S6K, PER2, and Caspase-3 protein levels was performed. The study demonstrated that circadian rhythm disruption caused an alteration in their food intake and decrease in primordial follicle numbers and an increase in the number of atretic follicles. It caused an increase in oxidative stress and a decrease in ZP3 expression in oocytes. Decreased protein levels of mTOR, p-mTOR, p70S6K, and PER2 were shown. The results showed that the circadian clock regulates mTORC1 through PER2 dependent mechanism and that decreased mTORC1 activity can contribute to premature aging of mouse ovary. In conclusion, these results suggest that the circadian clock may control ovarian aging by regulating mTOR signaling pathway through Per2 expression.

Effect of methylphenidate on the onset of puberty and reproductive organ development in rats.

Methylphenidate (MPH) is the first-line therapy for attention deficit hyperactivity disorder (ADHD) in children and adolescents. The aim of this study was to investigate the effects chronic MPH administration on reproductive parameters in both male and female pre-pubertal rats and reversibility of these effects. Sprague-Dawley rats were administered with 5 mg/kg MPH or saline orally from postnatal day (PND) 21 to PND60 and from PND21 to PND90. In addition, recovery groups from both sexes, in which MPH administration was stopped from PND60 to PND90 were included. Puberty onset, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol levels were determined. Histopathology of male and female reproductive organs was examined. Puberty onset was significantly early in the males (p<0.01), but late in females (p<0.05). In males, serum LH and FSH levels were similar. Testosterone levels tended to decrease in MPH-treated animals. Morphology of testes, epididymis and vas deferens was disrupted in MPH-treated animals, while it was improved in the recovery group. In females, estradiol levels decreased in MPH-treated group compared to controls, and elevated LH levels were detected in recovery group. Similar to the males, disruption in the reproductive organ histology was seen with morphological deterioration in basement membrane of the ovaries of MPH-treated groups. These adverse effects of MPH were recovered after drug cessation for 30 days. The present results demonstrate that MPH could affect the reproductive functions in both male and female rats. However, our findings also suggest that those effects are transient.

Design and characterization of dexamethasone loaded microsponges for the management of ulcerative colitis.

Ulcerative colitis is an inflammatory condition with ulcerations throughout the colon. The existing remedies have some limitations such as drug inactivation, poor absorption, and adverse reactions. The present study aimed to design novel microsponge formulations to enhance remission of the dexamethasone (as a model pharmaceutical ingredient) in the colon. Microsponges were prepared by using the quasi-emulsion technique. The optimal formulation was selected by applying the design of experiments approach which used methylcellulose (MC) (0.75-2%, w/w), polyvinylalcohol (PVA)(0.5-1%, w/w), and tween 80 (TW80) (1.5-2.5%, w/w). The critical quality attributes were selected as particle size and entrapment efficiency. The particle size and encapsulation efficiency were found as 140.38 ± 9.2 µm and 77.96 ± 3.4 %. After the optimization; morphological, thermal, and physicochemical characterization studies were performed. Ultimately, the optimal formulation was investigated by using the acetic acid-induced ulcerative colitis model in rats. The physicochemical characterization studies confirmed that the formulation components were compatible with each other. The in vitro release mechanisms were fitted to First order kinetics at pH 1.2 (R2:0.9563), and Korsmeyer-Peppas kinetics at pH 4.5 (R2: 0.9877), and pH 6.8 (R2: 0.9706). The medicated microsponges exhibited remarkable recovery compared to the control group of the in vivo ulcerative colitis model (p < 0.05). It could be concluded that microsponges were evaluated as a promising alternative drug delivery system for the management of ulcerative colitis.

Effect of rapamycin treatment in human seminoma TCam-2 cells through inhibition of G1-S transition.

Mammalian target of rapamycin (mTOR) is an important serine/threonine kinase that plays a critical role in several processes including cell cycle, protein synthesis, and energy metabolism. Due to its multiple roles and general dysregulation in cancer, the mTOR pathway is an important target in cancer therapy. However, studies on mTOR activity in seminoma are limited. Therefore, our aim was to investigate the expression of mTOR signaling pathway proteins in the TCam-2 cell line after rapamycin treatment. TCam-2 cells were treated with different concentrations of rapamycin (control (no rapamycin treatment), 4 nM, 20 nM, 100 nM, 500 nM, and 1000 nM rapamycin) for 48 h and 72 h. mTOR, p-mTOR, P70S6K, p-P70S6K, proliferating cell nuclear antigen (PCNA), and caspase-3 expression levels were analyzed by western blot. Apotosis and cell cycle were analyzed by flow cytometry. After 48 h of rapamycin administration, mTOR activity was significantly decreased at 1000 nM (p < 0.05). In addition, P70S6K acitivity significantly decreased in groups at all rapamycin concentrations (***p < 0.001, ****p < 0.0001). After 72 h of rapamycin administration, mTOR pathway activity were significantly decreased at 100, 500, and 1000 nM rapamycin-treated groups (p < 0.05). Moreover, P70S6K expression decreased in all treatment groups (****p < 0.0001). Caspase-3 expression were similar in all groups. While PCNA expression tended to decrease at 48 h in a dose-dependent manner, this decrease was not significant. We detected decreased PCNA expression at 1000 nM rapamycin at 72 h (p < 0.05). The rate of apoptosis increased especially at 1000 nM rapamycin at 72 h (***p < 0.001). On the other hand, according to the results of the cell cycle experiment, G1 phase arrest was detected at all rapamycin doses at 48 and 72 h (***p < 0.001). Our study indicated that 1000 nM rapamycin may inhibit TCam-2 seminoma cells growth by halting cell proliferation through inhibition of G1-S transition. Therefore, we believe that the findings obtained will contribute to the development of new treatment approaches for seminoma patients in the future and in the process of restoring testicular functions and preserving fertility.

Cell fate determination and Hippo signaling pathway in preimplantation mouse embryo.

First cell fate determination plays crucial roles in cell specification during early phases of embryonic development. Three classical concepts have been proposed to explain the lineage specification mechanism of the preimplantation embryo: inside-outside, pre-patterning, and polarity models. Transcriptional effectors of the Hippo signal pathway are YAP and TAZ activators that can create a shuttle between the cytoplasm and the nucleus. Despite different localizations of YAP in the cell, it determines the fate of ICM and TE. How the decisive cue driving factors that determine YAP localization are coordinated remains a central unanswered question. How can an embryonic cell find its position? The objective of this review is to summarize the molecular and mechanical aspects in cell fate decision during mouse preimplantation embryonic development. The findings will reveal the relationship between cell-cell adhesion, cell polarity, and determination of cell fate during early embryonic development in mice and elucidate the inducing/inhibiting mechanisms that are involved in cell specification following zygotic genome activation and compaction processes. With future studies, new biophysical and chemical cues in the cell fate determination will impart significant spatiotemporal effects on early embryonic development. The achieved knowledge will provide important information to the development of new approaches to be used in infertility treatment and increase the success of pregnancy.

The role of mitogen-activated protein kinase signaling pathway in endometriosis.

AIM: Endometriosis is an estrogen-dependent chronic inflammatory condition which causes pain, infertility, and predisposition for ovarian cancer. Endometriosis generates a unique microenvironment for survivability of endometriotic lesions which includes cell proliferation, differentiation, migration, and apoptosis. For these cellular activities, cascading activations of intracellular kinases are needed. Many kinase signaling pathways, IKKß/NK-κB pathway, PI3K/AKT/mTOR, and the mitogen-activated protein kinase (MAPK) pathways (ERK1/2, p38, and JNK), are activated in endometriosis. In this review, we focus on the role of MAPK pathways in endometriosis. METHODS: To identify the role of MAP Kinase signaling pathway in endometriosis we searched the Pubmed database using the search terms in various combinations "endometriosis," "endometrium," "ovary," "MAPK pathway," "ERK pathway," "p38 pathway," "JNK pathway," "estrogen," and "progesterone." RESULTS: According to the current literature, MAPK signaling pathway has various roles in generating microenvironment and survival of endometriosis. Abnormal MAPK activation in migration, implantation, growth, invasion into the pelvic structures, proliferation, and apoptosis leads to the form of endometriosis and to worsen the condition in patients with endometriosis. CONCLUSION: To further investigations on the effective and long-term endometriosis treatment, MAPK signaling pathways may be targeted. Molecular mechanism of MAPK signaling pathway in endometriosis should be more deeply understood and clinical trials should be more commonly performed for possible new endometriosis treatments to improve fertility and rescue endometriosis irreversibly.

Determination of c-Abl tyrosine kinase and mTERT catalytic subunit of telomerase expression level during prenatal-postnatal mouse ovary-testis development.

Expression levels of genes involved in the development of germ cells vary throughout the process from bipotential gonadal period to adult gonadal formation. In mice, developments of female and male reproductive system are regulated by germ cell-specific factors and hormones, and determinative days in this regulation are very important. c-Abl is a non-receptor tyrosine kinase with cellular functions including cell proliferation, growth and development. mTERT is involved in maintaining telomerase activity and proliferation of surviving cells. We suggested that c-Abl and mTERT might be important for the healthy development of prenatal and postnatal mouse ovary and testis. We aim to demonstrate localization and expressions of c-Abl and mTERT in crucial days of ovary and testis development in prenatal and postnatal period in mouse by immunofluorescence staining and qRT-PCR, respectively. The importance of c-Abl and mTERT expressions during the healthy gonadal development is indicated in the prenatal and postnatal gonadal development. Also, protein expression levels were detected by Western Blot in only postnatal ovary and testis. Determining the functions of the c-Abl and mTERT throughout the process will be important in terms of understanding the infertility cases in the female and male with future studies.

Interaction of the mTERT telomerase catalytic subunit with the c-Abl tyrosine kinase in mouse granulosa cells.

Context: Oocyte and granulosa cells (GCs) have bidirectional communication and GCs play an important role in folliculogenesis and proliferation of GCs is very important for the development of ovulatory follicle. DNA double-strand breaks activate c-Abl protein tyrosine kinase and c-Abl has a functional role in repairement of DNA and control of telomere.Objective: In this study, we hypothesized that c-Abl has a regulative role on mTERT in mouse ovarian granulosa cells (GCs) and we aimed to detect c-Abl and mTERT interaction in mouse primary culture of GCs.Materials and methods: Mouse ovarian granulosa cell were cultured and siRNA-mediated knockdown approach was used to knockdown c-Abl expression.Results: We showed c-Abl and mTERT immunolocalization in vivo and in vitro mouse GCs. c-Abl and mTERT were constitutively expressed in mouse granulosa cells and c-Abl presented more intense expression in granulosa cells than mTERT expression. The interaction of the c-Abl-mTERT is supported by the exhibition that c-Abl siRNA knockdown cells show decreased mTERT expression. We also present an interaction between c-Abl and mTERT by immunoprecipitation. In addition, our results indicated that the down-regulation of c-Abl was also accompanied by reduced expression of proliferating cell nuclear antigen (PCNA) in GCs.Conclusions: We suggest that mTERT may associate with the c-Abl in mouse GCs and the interactions between c-Abl and mTERT suggest a role for c-Abl in the regulation of telomerase function and proliferation in mouse granulosa cells.

Gonadal development and sex determination in mouse.

The development of primordial germ cells and gonads are determinants of reproductive health and fertility. Although the gonadal development process is similar for both genders, the gender-determining process and the mechanism of development of female and male gonads have different molecular mechanisms. Spermatogenesis and oogenesis are also included in this process for a healthy gonadal development. Many specific molecular signaling pathways play role in oogenesis and spermatogenesis and it is important to know at which stage these factors are effective, to understand the mechanism of a healthy gonadal development. With this review, we defined the importance of stage specific genes expressing during the events such as oogenesis and spermatogenesis with the prenatal and postnatal gonadal development. It will be important to know about the cellular signals involved in the control of the gonadal development.

Comparison of the Effects of Dovitinib and Bevacizumab on Reducing Neovascularization in an Experimental Rat Corneal Neovascularization Model.

PURPOSE: To compare the inhibitory effects of dovitinib and bevacizumab for treatment of corneal neovascularization (CNV). METHODS: Thirty-nine adult female Sprague Dawley rats weighing 180 to 250 g were used. CNV was induced by silver nitrate in the right eye of each rat. After the chemical burn, the animals were randomized into 5 groups. Group 1 did not receive any chemical substance. Group 2 received dimethyl sulfoxide, group 3 received bevacizumab 5 mg/mL, group 4 received dovitinib 5 mg/mL, and group 5 received bevacizumab 5 mg/mL + dovitinib 5 mg/mL topically administered twice daily for 14 days. On the 14th day, slit-lamp examination was performed, and anterior segment photographs were taken. The corneal neovascular area was measured on photographs as the percentage of the cornea's total area using computer imaging analysis. The corneal sections were stained with hematoxylin and eosin for histopathological examination. RESULTS: A statistically significant decrease in the percentage of CNV was found in all treatment groups (group 3, group 4, and group 5) compared with the control group (group 1) (P < 0.01). A statistically significant difference in the percentage of CNV was found among group 3, group 4, and group 5 (P = 0.003). The percentage of CNV in group 4 was significantly higher than that in group 3 and group 5 (P1 = 0.004; P2 = 0.006). There was no statistically significant difference in the percentage of CNV between group 3 and group 5 (P = 0.228). CONCLUSIONS: Dovitinib is a newly developed multitargeted tyrosine kinase inhibitor. Topical administration of dovitinib effectively inhibited CNV, but this effect of dovitinib was found less than topical bevacizumab.

The effect of nutrient supplementation in the management of polycystic ovary syndrome-associated metabolic dysfunctions: A critical review

Polycystic ovary syndrome (PCOS) is complex heterogeneous disorder that has several aspects in terms of pathology such as metabolic, endocrine, reproductive, and psychological. However, the etiology of PCOS remains poorly understood. Several studies suggest that insulin resistance and hyperandrogenism play a central role in the progression of PCOS pathophysiology. Therefore, common treatment strategies of PCOS are based on lifestyle modification, which include exercise, diet, and nutrient supplementation therapy. Recent studies have recommended some nutrients such as vitamins, minerals, and vitamin-like nutrients for the therapy of PCOS because each has at least one functional property in PCOS-induced pathways. Therefore, it is claimed that the cause of PCOS could be vitamin or mineral deficiency. This review aims to provide a critical literature survey on nutritional supplementation for the treatment of PCOS-associated endocrine and metabolic dysfunctions and discuss the role of nutrients in the management of PCOS in view of the clinical trials and experimental studies.

Expression of CCM2 and CCM3 during mouse gonadogenesis.

PURPOSE: Three cerebral cavernous malformation (CCM) proteins, CCM1, CCM2, and CCM3, regulate cell-cell adhesion, cell shape and polarity, and most likely cell adhesion to extracellular matrix. Recently, CCM2 and CCM3 are known to be expressed in control and varicocele-induced rat testes, but little is known about these proteins during gonadogenesis. This led us to study the CCM proteins during the mouse gonadogenesis. METHODS: Neonatal (PND 0), postnatal, and adult mice testes and ovaries were obtained from mice. CCM2 and CCM3 expression were analyzed during mouse testicular and ovarian development by immunohistochemistry and quantitative real-time PCR. RESULTS: The results showed that in both sexes, Ccm2 and Ccm3 mRNA and protein were first detectable after gonadogenesis when the gonads were well differentiated and remained present until the adult stage. In the testis, CCM2 and CCM3 expression were restricted to the nuclei of Sertoli cells, suggesting a conserved role in testicular differentiation. In the ovary, the CCM2 and CCM3 proteins were localized in the cytoplasm of oocytes, suggesting an unexpected role during oogenesis. Quantitative real-time PCR (qRT-PCR) results showed that expression of Ccm2 and Ccm3 genes could play a role in the regulation of mouse gonadogenesis translational activation upon testicular and ovarian development. CONCLUSIONS: The localization of CCM2 and CCM3 proteins show their different functions for CCM2 and CCM3 which may have important roles in testicular and ovarian differentiation. In conclusion, CCM2 and CCM3 may be involved in establishing the differential expression pattern in developing mouse testis and ovary.

The p38 MAPK signalling pathway is required for glucose metabolism, lineage specification and embryo survival during mouse preimplantation development.

Preimplantation embryo development is an important and unique period and is strictly controlled. This period includes a series of critical events that are regulated by multiple signal-transduction pathways, all of which are crucial in the establishment of a viable pregnancy. The p38 mitogen-activated protein kinase (MAPK) signalling pathway is one of these pathways, and inhibition of its activity during preimplantation development has a deleterious effect. The molecular mechanisms underlying the deleterious effects of p38 MAPK suppression in early embryo development remain unknown. To investigate of the effect of p38 MAPK inhibition on late preimplantation stages in detail, we cultured 2-cell stage embryos in the presence of SB203580 for 48 h and analysed the 8-cell, morula, and blastocyst stages. We determined that prolonged inhibition of the p38 MAPK altered the expression levels of Glut1 and Glut4, decreased glucose uptake during the 8-cell to blastocyst transition, changed the expression levels of transcripts which will be important to lineage commitment, including Oct4/Pou5f1, Nanog, Sox2, and Gata6, and increased cell death in 8-16 cell stage embryos onwards. Strikingly, while the expression levels of Nanog, Gata6 and Oct4/Pou5f1 mRNAs were significantly decreased, Sox2 mRNA was increased in SB203580-treated blastocysts. Taken together, our results provide important insight into the biological processes controlled by the p38 MAPK pathway and its critical role during preimplantation development.

Protective effect of chemically modified SOD on lipid peroxidation and antioxidant status in diabetic rats.

Reactive oxygen species mediated oxidative stress play an important role on the injury of tissue damage and increased attention has been focused on the role of free radicals in diabetes mellitus (DM). In the present study firstly superoxide dismutase (SOD) enzyme was chemically modified with two different polymer and physicochemical properties of these conjugates clearly analyzed. Then, the stability of carboxymethylcellulose-SOD (CMC-SOD) and poly methyl vinyl ether-co-maleic anhydride-SOD (PMVE/MA-SOD) conjugates was investigated against temperature and externally added H2O2. Moreover, we investigated the effect of chemically modified SOD enzyme on lipid peroxidation and antioxidant status in streptozotocin (STZ)-induced diabetic rats. PMVE/MA-SOD conjugate treatment significantly reduced MDA level compared with the control groups, native and CMC-SOD conjugate treated groups in brain, kidney and liver tissue. GSH and SOD enzyme activity in diabetic groups was significantly increased by treatment of CMC-SOD and PMVE/MA-SOD conjugates. The protective effects on degenerative changes in diabetic rats were also further confirmed by histopathological examination. This study provides the preventative activity of SOD-polymer conjugates against complication of oxidative stress in experimentally induced diabetic rats. These results suggest that chemically modified SOD is effective on the oxidative stress-associated disease and offer a therapeutic advantage in clinical use.

The mechanism of mTOR (mammalian target of rapamycin) in a mouse model of polycystic ovary syndrome (PCOS).

Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder affecting 5-10% of women in reproductive age that is characterized by hyperandrogenism, oligo- or anovulation and infertility. However the pathophysiology of PCOS still remains unknown. The mammalian target of rapamycin (mTOR) is a central component that regulates various processes including cell growth, proliferation, metabolism, and angiogenesis. mTOR signaling cascade has recently been examined in ovarian follicles where it regulates granulosa cell proliferation and differentiation. mTOR functions as two complexes, mTOR complex 1 and 2. Therefore, we hypothesized that mTORC1 and/or 2 may have important role in proliferation of theca and granulosa cells in PCOS. In the present study, we sought to determine the mTOR signaling pathway in PCOS mouse ovary. We designed 3 groups: Control (C, no treatment), PCOS (P, The injection of DHEA (6 mg/100 g BW in 0.1 ml of sesame oil) (s.c) for 20 consecutive days), Vehicle (V, daily (s.c) sesame oil alone injection). Our results showed that mTORC1 and mTORC2-mediated signaling may play a role in PCOS mouse ovary. These findings provide evidence that mTORC1 and mTORC2 may have responsibility in increased ovarian follicular cell proliferation and growth in PCOS. Consequently, these results suggest that the mTOR signaling pathways (mTORC1 and mTORC 2) may create new clinical strategies to optimize developmental competence of PCOS should target correction of the entire follicle growth, oocyte development process and anovulatory infertility in PCOS.

mTOR controls ovarian follicle growth by regulating granulosa cell proliferation.

We have shown that inhibition of mTOR in granulosa cells and ovarian follicles results in compromised granulosa proliferation and reduced follicle growth. Further analysis here using spontaneously immortalized rat granulosa cells has revealed that mTOR pathway activity is enhanced during M-phase of the cell cycle. mTOR specific phosphorylation of p70S6 kinase and 4E-BP, and expression of Raptor are all enhanced during M-phase. The predominant effect of mTOR inhibition by the specific inhibitor Rapamycin (RAP) was a dose-responsive arrest in the G1 cell cycle stage. The fraction of granulosa cells that continued to divide in the presence of RAP exhibited a dose-dependent increase in aberrant mitotic figures known as anaphase bridges. Strikingly, estradiol consistently decreased the incidence of aberrant mitotic figures. In mice treated with RAP, the mitotic index was reduced compared to controls, and a similar increase in aberrant mitotic events was noted. RAP injected during a superovulation regime resulted in a dose-dependent reduction in the numbers of eggs ovulated. Implications for the real-time regulation of follicle growth and dominance, including the consequences of increased numbers of aneuploid granulosa cells, are discussed.

The Abelson tyrosine kinase (c-Abl) expression on the mouse uterus and placenta during gestational period.

c-Abl is a protein tyrosine kinase which has very important roles in signal transduction, control of the cell cycle, cell motility, proliferation, and inhibition of apoptosis. We hypothesized that c-Abl may play an important role on uterine remodeling during pre-receptive, receptive and non-receptive endometrium. Our aim is to investigate the expression of c-Abl protein tyrosine kinase in uterine remodeling and placental development in mouse gestational stage. We performed c-Abl immunohistochemistry on mouse uterine tissue sections on days 1-9, 11, 13, and 15 of pregnancy. c-Abl was highly upregulated in the uterine luminal epithelium and other endometrial structures including glands and blood vessels in pre-receptive and receptive endometrium. Therefore these results demonstrate a role for c-Abl in uterine remodeling during decidualization, implantation, and placentation throughout gestation.

Spatial and temporal expression of vasodilator-stimulated phosphoprotein (VASP) in fetal and adult human cerebral cortex.

Vasodilator-stimulated phosphoprotein (VASP) is a member of the Ena/VASP protein family and was for the first time identified in human platelets. VASP plays a role for cell adhesion and cell migration because of E/DFPPPPXD/E amino acid sequence in its structure which gives reaction with focal adhesion proteins. In this study we suggest that VASP expression may have important role for neural cell migration, differentiation, axonal growth and angiogenesis during prenatal cerebral cortical development. Our aim is to detect VASP expression by means of immunohistochemistry and Western blot analysis in developing human neocortex and adult brain cortex (n=12 samples from first, second, and third trimesters and n=3 adult normal cerebral cortex). Our results suggest that VASP showed different immunostaining patterns between cerebral cortical plates in prenatal and adult human brain samples. We observed that the expression patterns of the VASP protein are clearly identified in fibers, cytoplasm of neural cells and endothelial cells of vessels. We detected that VASP indicates progressive expression from the adult brain to second trimester neocortexes. Therefore, we suggest that VASP may play a crucial role in the regulation of human neonatal cerebral cortical development.