Linagliptin in combination with insulin suppresses apoptotic unfolded protein response in ovaries exposed to type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is one of the main causes of ovarian atresia, but its molecular effect on the ovaries is not fully understood. Accumulating evidence suggests that T1DM causes excessive endoplasmic reticulum (ER) stress and insufficient adaptive unfolded protein response that triggers proapoptotic signaling pathways in ovarian tissue. In addition, problems such as amenorrhea and infertility, which are frequently seen in women with T1DM, continue despite the intensification of insulin therapy and improvement of metabolic control. Therefore new, and adjunctive treatments for women with T1DM need to be explored. We aimed to examine how the use of linagliptin, which has blood sugar-lowering effects and high antioxidant activity, together with insulin affects the expression levels of proteins and genes that play a role in ER stress in type 1 diabetic mouse ovaries. Eighty-four Balb/C 6-week-old female mice were randomly divided into seven groups: control, vehicle, diabetes + insulin, diabetes + linagliptin, diabetes + linagliptin + insulin, diabetes + TUDCA, and diabetes + TUDCA + insulin. TUDCA (an inhibitor of ER stress) groups are positive control groups created to compare linagliptin groups in terms of ER stress. Linagliptin and TUDCA were given by oral gavage and 1U insulin was administered subcutaneously for 2 weeks. A significant decrease was observed in the MDA and NOX1 levels and the number of atretic follicles in the ovaries of the diabetes + linagliptin + insulin group compared to the diabetes + insulin group. The use of linagliptin and insulin increased the expression of pro-survival XBP1s transmembrane protein and decreased the expression of proapoptotic ATF4, pJNK1/2, cleaved caspase 12, and cleaved caspase 3 in mouse ovaries. Our study provides new therapeutic evidence that linagliptin administered in addition to insulin induces ER stress mechanism-dependent survival in ovaries with type 1 diabetes.

Expression levels of tam receptors and ligands in the testes of rats exposed to short and middle-term 2100 MHz radiofrequency radiation.

With advances in technology, the emission of radiofrequency radiation (RFR) into the environment, particularly from mobile devices, has become a growing concern. Tyro 3, Axl, and Mer (TAM) receptors and their ligands are essential for spermatogenesis and testosterone production. RFR has been shown to induce testicular cell apoptosis by causing inflammation and disrupting homeostasis. This study aimed to investigate the role of TAM receptors and ligands in the maintenance of homeostasis and elimination of apoptotic cells in the testes (weeks), short-term sham exposure (sham/1 week), and middle-term sham exposure (sham/10 weeks). Testicular morphology was assessed using hematoxylin-eosin staining, while immunohistochemical staining was performed to assess expression levels of TAM receptors and ligands in the testes of all groups. The results showed that testicular morphology was normal in the control, sham/1 week, and sham/10 weeks groups. However, abnormal processes of spermatogenesis and seminiferous tubule morphology were observed in RFR exposure groups. Cleaved Caspase 3 immunoreactivity showed statistically significant difference in 1 and 10 weeks exposure groups compared to control group. Moreover, there was no significant difference in the immunoreactivity of Tyro 3, Axl, Mer, Gas 6, and Pros 1 between groups. Moreover, Tyro 3 expression in Sertoli cells was statistically significantly increased in RFR exposure groups compared to the control. Taken together, the results suggest that RFR exposure negatively affects TAM signalling, preventing the clearance of apoptotic cells, and this process may lead to infection and inflammation. As a result, rat testicular morphology and function may be impaired.

BMP signalling is required for extra-embryonic ectoderm development during pre-to-post-implantation transition of the mouse embryo.

At implantation, the mouse embryo undergoes a critical transformation which requires the precise spatiotemporal control of signalling pathways necessary for morphogenesis and developmental progression. The role played by such signalling pathways during this transition are largely unexplored, due to the inaccessibility of the embryo during the implantation when it becomes engulfed by uterine tissues. Genetic studies demonstrate that mutant embryos for BMPs die around gastrulation. Here we have aimed to dissect the role of BMPs during pre-to post-implantation transition by using a protocol permitting the development of the embryo beyond implantation stages in vitro and using stem cells to mimic post-implantation tissue organisation. By assessing both the canonical and non-canonical mechanisms of BMP, we show that the loss of canonical BMP activity compromises the extra-embryonic ectoderm development. Our analyses demonstrate that BMP signalling maintains stem cell populations within both embryonic/extra-embryonic tissues during pre-to post-implantation development. These results may provide insight into the role played by BMP signalling in controlling early embryogenesis.

The effects of acute and chronic exposure to 900 MHz radiofrequency radiation on auditory brainstem response in adult rats.

The aim of this study was to determine the effects of short and long-term RFR exposure on ABR by evaluating lipid peroxidation and antioxidant status in adult rats. Sixty male albino Wistar rats were randomly divided into four groups. S1:1 week sham, S10:10 weeks sham, E1:1 week RFR, E10:10 weeks RFR. Experimental group rats were exposed to RFR 2 h/day, 5 days/week during the test period. Sham rats were kept in the same conditions without RFR. After the experiment, ABRs were recorded from the mastoids of rats using tone burst acoustic stimuli. Biochemical investigations in rat brain and ultrastructural analysis in temporal cortex were performed. ABR wave I latency prolonged in E1-group and shortened in E10-group compared to their shams. TBARS level increased in E1-group, decreased in E10-group, on the contrary, SOD and CAT activities and GSH level decreased in E1-group, increased in E10-group compared to their sham groups. Edema was present in the neuron and astrocyte cytoplasms and astrocyte end-feet in both E1 and E10 groups. Our results suggest that 900 MHz RFR may have negative effects on the auditory system in acute exposure and no adverse effects in chronic exposure without weekends.

Dehydroepiandrosterone supplementation attenuates ovarian ageing in a galactose-induced primary ovarian insufficiency rat model.

PURPOSE: Almost every female classic galactosemia patient develops primary ovarian insufficiency (POI). The unique pathophysiology of classic galactosemia, with a severely reduced follicle pool at an early age, requires a new therapeutic approach. This study evaluated the effect of dehydroepiandrosterone (DHEA) on ovarian tissue in a galactose-induced POI rat model. METHODS: Pregnant rats were fed with either a normal or a 35% galactose-containing diet from day 3 of conception continuing through weaning of the litters. Galactose-exposed female offspring were further divided into 5 groups on PND21. The first group received no application. Treatment groups were fed orally by gavage once daily with sesame oil (group 2), or DHEA at doses of 0.1 mg/kg (group 3), 1 mg/kg (group 4) or 10 mg/kg (group 5) until PND70. Fertility rates of mothers with galactosemia, body weights (BWs), and ovarian weights of the litters from PND21 to PND70 were recorded. Ovarian follicle count, immunohistochemistry for proliferation and apoptosis marker expressions and TUNEL for cell death assessment were performed in offspring ovaries. RESULTS: Decreased fertility, ovarian/body weights were observed under galactosemic conditions, together with decreased follicle number and increased atresia. Improved postnatal development, primordial follicle recruitment and follicular growth were observed after DHEA treatment. After DHEA treatment, the expression of Ki67 protein was found to be increased; elevated expression of cleaved-caspase-3 under galactosemia was found to be reduced. CONCLUSIONS: Our data suggests that DHEA treatment may be a potentially useful clinical therapy to improve ovarian ageing in women with POI-induced by galactosemia.

Spontaneous Idiopathic Cerebrospinal Fluid Rhinorrhea.

Cerebrospinal fluid rhinorrhea is described as cerebrospinal fluid flow through the nose due to the abnormal connection of the subarachnoid space and sinonasal cavity. Spontaneous idiopathic rhinorrhea is a rarely seen disease. Besides the patient's clinical presentation detailed radiological evaluation and other invasive procedures must be carried out to confirm the diagnosis. Its treatment is compelling due to high recurrence rates. In the treatment algorithm when conservative treatment modalities had been proven inadequate, surgical repair must follow in order. In this paper the authors present the details of 2 cases of spontaneous rhinorrhoea patients.

Comparative Analysis of the Healing Effects of the Transplanted Cell Sheets to the Experimentally Injured Maxillary Sinuses.

BACKGROUND: In our study, the authors aimed to obtain a live and functional sinus epithelium with mesenchymal stem cells and nasal mucosa epithelial cells from rabbits which are cultured in temperature-responsive culture plates to get a single-layer. METHODOLOGY/PRINCIPAL: Twenty-two female New Zealand rabbits were included in the study. Two of them were used to obtain mesenchymal stem cells. A total of 40 maxillary sinuses were randomly divided into 5 groups: 1) control group which is used to investigate normal rabbit maxillary mucosa, 2) secondary healing group, 3) mesenchymal stem cell graft group, 4) differentiated mesenchymal stem cell group, and 5) nasal mucosal graft group. The animals were sacrificed at the 28th day after the surgery.Scanning electron microscopy, transmission electron microscopy, and immunohistochemical investigations were performed. RESULTS: With these investigations, it was shown that; all graft groups were histologically better than secondary healing group and when the authors compared the graft groups, differentiated mesenchymal stem cell group were the best. CONCLUSION: Our study results showed that endoscopic sinus surgery and treatment with cell sheets, which were generated in temperature-responsive culture dishes, had more functional respiratory epithelium.

Superovulation alters embryonic poly(A)-binding protein (Epab) and poly(A)-binding protein, cytoplasmic 1 (Pabpc1) gene expression in mouse oocytes and early embryos.

Embryonic poly(A)-binding protein (EPAB) and poly(A)-binding protein, cytoplasmic 1 (PABPC1) play critical roles in translational regulation of stored maternal mRNAs required for proper oocyte maturation and early embryo development in mammals. Superovulation is a commonly used technique to obtain a great number of oocytes in the same developmental stages in assisted reproductive technology (ART) and in clinical or experimental animal studies. Previous studies have convincingly indicated that superovulation alone can cause impaired oocyte maturation, delayed embryo development, decreased implantation rate and increased postimplantation loss. Although how superovulation results in these disturbances has not been clearly addressed yet, putative changes in genes related to oocyte and early embryo development seem to be potential risk factors. Thus, the aim of the present study was to determine the effect of superovulation on Epab and Pabpc1 gene expression. To this end, low- (5IU) and high-dose (10IU) pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotrophin (hCG) were administered to female mice to induce superovulation, with naturally cycling female mice serving as controls. Epab and Pabpc1 gene expression in germinal vesicle (GV) stage oocytes, MII oocytes and 1- and 2-cell embryos collected from each group were quantified using quantitative reverse transcription-polymerase chain reaction. Superovulation with low or high doses of gonadotropins significantly altered Epab and Pabpc1 mRNA levels in GV oocytes, MII oocytes and 1- and 2-cell embryos compared with their respective controls (P<0.05). These changes most likely lead to variations in expression of EPAB- and PABPC1-regulated genes, which may adversely influence the quality of oocytes and early embryos retrieved using superovulation.

Pentoxifylline Alleviates Early Brain Injury in a Rat Model of Subarachnoid Hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe cerebrovascular disease frequently caused by ruptured aneurysms. Early brain injury (EBI) is the primary cause of morbidity and mortality in patients diagnosed with SAH and is associated with increased intracranial pressure, decreased cerebral blood flow and cerebral ischemia. Pentoxifylline (PTX) is a methylxanthine derivative clinically proven to improve perfusion in the peripheral microcirculation and has been shown to have neuroprotective effects in brain trauma and global cerebral ischemia in experimental animal models. This study aimed to determine the effect of PTX in experimental SAH, which has not been investigated yet. METHODS: An experimental SAH model was induced in male Wistar rats by autologous blood injection into the prechiasmatic cistern, and PTX was injected intraperitoneally immediately after SAH. The effects of PTX were evaluated 24 h after SAH via assessing the cerebral ultrastructure via transmission electron microscopy (TEM). Brain edema, blood-brain barrier (BBB) permeability, red blood cell deformability, tumor necrosis factor-alpha (TNF-alpha), nitrite-nitrate levels and apoptotic neuron death were also determined 24 h after SAH. The BBB permeability was measured by Evans blue (EB) extravasation, erythrocyte deformability was determined by filtration technique, and TNF-alpha and reactive nitrogen metobolites were analyzed in brain tissue by ELISA and spectral analysis, respectively. Apoptotic neurons were determined in brain sections by cleaved caspase-3 immunohistochemical analysis, and expression intensity was quantified using image J software. RESULTS: Cerebral ultrastructure in SAH group animals revealed intense perivascular edema and distortion in the astrocyte foot processes. PTX treatment attenuated structural deterioration due to SAH. Brain water content, BBB permeability, TNF-alpha, nitrite-nitrate levels and apoptotic neuronal death were significantly increased 24 h after SAH and were significantly alleviated by PTX treatment. There was no significant change in red cell deformability after SAH. CONCLUSIONS: Our results show that PTX reduces brain edema, BBB permeability, TNF-alpha expression, reactive nitrogen metobolites and apopotosis in experimental SAH. Based on our findings we suggest that PTX exerts neuroprotection against SAH-induced EBI, which might be associated with the inhibition of inflammation and apoptotic neuronal cell death.

Differential expression pattern of Twist1 in mouse preimplantation embryos suggests its multiple roles during early development.

PURPOSE: The purpose of the present study is to understand Twist-related protein 1 (Twist1) spatiotemporal expression patterns and functions during early embryo development. METHODS: We performed whole-mount double immunofluorescence staining and reverse transcription (RT)-PCR analysis of the Twist1 protein and gene throughout the preimplantation development in mice. RESULTS: We determined that after compaction, the expression of Twist1 becomes developmentally differentiated and targeted in the inner cells of embryos. In blastocysts at E4.5, uniform staining of the inner cell mass was apparent, and it had been gradually translocated to the nucleus of hatched embryonic cells at E4.75. Furthermore, the effect of potential regulators of Twist on its expression level during blastocyst development was also sought. Accordingly, Twist1 expression appeared to be upregulated in both mRNA and protein level following culture of embryos in the presence of high glucose. CONCLUSIONS: Our study revealed the dynamic Twist localization within the early stage of embryo. The results are discussed in terms of potential roles of Twist1 in the processes of lineage segregation, hatching, and implantation in post-compaction embryos and in blastocysts.

The poly(A)-binding protein genes, EPAB, PABPC1, and PABPC3 are differentially expressed in infertile men with non-obstructive azoospermia.

PURPOSE: Azoospermia is one of the major causes of male infertility and is basically classified into obstructive (OA) and non-obstructive azoospermia (NOA). The molecular background of NOA still largely remains elusive. It has been shown that the poly(A)-binding proteins (PABPs) essentially play critical roles in stabilization and translational control of the mRNAs during spermatogenesis. METHODS: In the present study, we aim to evaluate expression levels of the PABP genes, EPAB, PABPC1, and PABPC3, in the testicular biopsy samples and in the isolated spermatocyte (SC) and round spermatid (RS) fractions obtained from men with various types of NOA including hypospermatogenesis (hyposperm), RS arrest, SC arrest, and Sertoli cell-only syndrome (SCO). RESULTS: In the testicular biopsy samples, both PABPC1 and PABPC3 mRNA expressions were gradually decreased from hyposperm to SCO groups (P < 0.05), whereas there was no remarkable difference for the EPAB expression among groups. The expression levels of cytoplasmically localized PABPC1 and PABPC3 proteins dramatically reduced from hyposperm to SCO groups (P < 0.05). In the isolated SC and RS fractions, the EPAB, PABPC1, and PABPC3 mRNA expressions were gradually decreased from hyposperm to SC arrest groups (P < 0.05). Similarly, both PABPC1 and PABPC3 proteins were expressed at higher levels in the SC and RS fractions from hyposperm group when compared to the SC and RS fractions from either RS arrest or SC arrest group (P < 0.05). CONCLUSION: Our findings suggest that observed significant alterations in the PABPs expression may have an implication for development of different NOA forms.

Cell fate regulation during preimplantation development: a view of adhesion-linked molecular interactions.

In the developmental process of the early mammalian embryo, it is crucial to understand how the identical cells in the early embryo later develop different fates. Along with existing models, many recently discovered molecular, cellular and developmental factors play roles in cell position, cell polarity and transcriptional networks in cell fate regulation during preimplantation. A structuring process known as compaction provides the "start signal" for cells to differentiate and orchestrates the developmental cascade. The proper intercellular junctional complexes assembled between blastomeres act as a conducting mechanism governing cellular diversification. Here, we provide an overview of the diversification process during preimplantation development as it relates to intercellular junctional complexes. We also evaluate transcriptional differences between embryonic lineages according to cell- cell adhesion and the contributions of adhesion to lineage commitment. These series of processes indicate that proper cell fate specification in the early mammalian embryo depends on junctional interactions and communication, which play essential roles during early morphogenesis.

Activation of neuroimmune pathways increases therapeutic effects of radiotherapy on poorly differentiated breast carcinoma.

Recent studies document the importance of neuronal dysfunction in cancer development and metastasis. We reported previously that both depletion of neuropeptides in capsaicin-sensitive sensory nerve endings and vagotomy increases metastasis of triple negative breast carcinoma. Of the sensory neuropeptides, Substance P (SP) is distributed widely for regulation of immune functions. We therefore examined the affects of continuous exposure to low doses of SP on brain metastatic cells of the mouse breast carcinoma (4TBM) in the presence of radiotherapy (RT) thought to increase antigenicity of cancer cells. 4TBM cells have a cancer stem cell phenotype and induce extensive visceral metastasis after orthotopic inoculation into the mammary pad. Results demonstrated that SP treatment decreases the number of tumor-infiltrating myeloid-derived suppressor cells as well as the TNF-α response to LPS challenge. SP also increased CD4+Cd25(bright) cells in draining lymph nodes of tumor-bearing animals and IFN-γ secretion from leukocyte culture prepared from lymph nodes and spleens of tumor-bearing animals. SP also prevented tumor-induced degeneration of sensory nerve endings and altered release of angiogenic factors from cancer-associated fibroblasts (CAF) and tumor explants. In accordance with these observed immunological effects, combination treatment of continuous SP with a single dose of RT induced complete tumor regression and significantly reduced or prevented metastasis in 50% of the animals while suppressing primary tumor growth and metastasis in the remaining mice. These original findings demonstrate that SP through neuroimmune modulation can prevent formation of immune suppression in the tumor microenvironment, enhance cytotoxic immunity in the presence of RT and prevent metastatic growth.

Epab and Pabpc1 are differentially expressed in the postnatal mouse ovaries.

PURPOSE: Embryonic poly(A)-binding protein (EPAB) and poly(A)-binding protein, cytoplasmic 1 (PABPC1) bind poly(A) tails of mRNAs and mediate their translational regulation in germ cells and early preimplantation embryos. Although expression patterns and possible functions of the Epab and Pabpc1 genes have been examined in vertebrate germ cells and early embryos, their expression levels and cellular localizations in the postnatal mouse ovaries remained elusive. METHODS: In the present study, we first aimed to characterize expression levels of the Epab and Pabpc1 genes in the prepubertal (1-, 2-, and 3-week old), pubertal (4-, 5-, and 6-week old), postpubertal (16-week and 18-week old), and aged (52-, 60-, and 72-week old) mouse ovaries by using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Epab mRNA was predominantly expressed in the prepubertal ovaries when compared to later developmental periods. However, Pabpc1 transcript was highly generated in the prepubertal and pubertal mouse ovaries except for 1-week old ovary than those of other developmental terms. In the prepubertal mouse ovaries, RNA in situ hybridization localized both Epab and Pabpc1 transcripts in the cytoplasm of oocytes and granulosa cells of all follicular stages. Consistently, Epab and Pabpc1 gene expression were detected in the cumulus cells and MII oocytes obtained from cumulus oocyte complexes (COCs). Ovarian follicle counting in the postnatal ovaries revealed that total number of follicles was higher in the prepubertal ovaries in comparison with later stages of development. CONCLUSION: As a result, Epab and Pabpc1 expression exhibit differences at postnatal ovary development stages and both genes are transcribed in the granulosa cells and oocytes. These findings suggest that EPAB may predominantly play roles in translational regulation of the mRNAs during early oogenesis and folliculogenesis, but PABPC1 most likely perform these roles in the later terms of ovarian development along with EPAB protein.

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.

Hypertension alters phosphorylation of VASP in brain endothelial cells.

Hypertension impairs cerebral vascular function. Vasodilator-stimulated phosphoprotein (VASP) mediates active reorganization of the cytoskeleton via membrane ruffling, aggregation and tethering of actin filaments. VASP regulation of endothelial barrier function has been demonstrated by studies using VASP(-/-) animals under conditions associated with tissue hypoxia. We hypothesize that hypertension regulates VASP expression and/or phosphorylation in endothelial cells, thereby contributing to dysfunction in the cerebral vasculature. Because exercise has direct and indirect salutary effects on vascular systems that have been damaged by hypertension, we also investigated the effect of exercise on maintenance of VASP expression and/or phosphorylation. We used immunohistochemistry, Western blotting and immunocytochemistry to examine the effect of hypertension on VASP expression and phosphorylation in brain endothelial cells in normotensive [Wistar-Kyoto (WKY)] and spontaneously hypertensive (SH) rats under normal and exercise conditions. In addition, we analyzed VASP regulation in normoxia- and hypoxia-induced endothelial cells. Brain endothelial cells exhibited significantly lower VASP immunoreactivity and phosphorylation at the Ser157 residue in SHR versus WKY rats. Exercise reversed hypertension-induced alterations in VASP phosphorylation. Western blotting and immunocytochemistry indicated reduction in VASP phosphorylation in hypoxic versus normoxic endothelial cells. These results suggest that diminished VASP expression and/or Ser157 phosphorylation mediates endothelial changes associated with hypertension and exercise may normalize these changes, at least in part, by restoring VASP phosphorylation.

The Evaluation of Relationship Between Body Mass Index and Nasal Geometry Using Objective and Subjective Methods.

INTRODUCTION: It is known that obesity causes obstructive sleep apnea syndrome by increasing upper airway resistance. Also, obese patients are admitted to the ear, nose, and throat clinic very often because of nasal obstruction complaint. The aim of this study is to identify the change and relation among body mass index (BMI), nasal resistance, reduction in nasal ariflow, nasal anatomy, and patients' subjective complaints. MATERIAL AND METHOD: A total of 67 patients admitted to our clinic between August 2013 and January 2014 were included in the study.The study group comprised 33 patients who had a chief complaint-nasal obstruction and the other group consisted of 34 patients who had no complaint and nasal pathology. Both the groups were checked with acoustic rhinometry (AR), active anterior rhinomanometer, nasal obstruction symptom evaluation (NOSE), and visual analog study (VAS) questionnaire. RESULTS: There is a significant statistical correlation between the body mass increase and VAS and NOSE score increase (P < 0.05). But the authors did not find any statistically significant relation between BMI and total inspiratory and expiratory MR and MF measured by anterior active rhinomanometer and left and right nasal cavity MCA, and volume measured by acoustic rhinometery (P > 0.05). CONCLUSIONS: Contrary to belief, obesity does not change the nasal resistance, airflow, and anatomy but it can cause subjective nasal complaints.

Telomere length and telomerase activity during oocyte maturation and early embryo development in mammalian species.

Telomeres are located at the ends of all eukaryotic chromosomes and protect them from deleterious events such as inappropriate DNA repair, illegitimate recombination or improper segregation of the chromosomes during mitotic or meiotic divisions. However, telomeres gradually shorten primarily due to successive rounds of genomic DNA replication and also as the result of the adverse effects of oxidative stress, genotoxic agents, diseases related to ageing and environmental factors on the nuclear materials of dividing or non-dividing cells. Germline cells, proliferative granulosa cells, early embryos, stem cells, highly proliferative somatic cells and many cancer cells contain the enzyme telomerase so that they are capable of elongating the shortened telomeres. Although numerous studies have revealed the length of telomeres and telomerase activity in oocytes, granulosa cells and early embryos, only a few studies have analyzed and compared the work performed on distinct mammalian species. In this comprehensive review article, we compare and discuss telomere length and telomerase activity in oocytes, granulosa cells and early embryos in different mammalian species including mice, bovines and humans.

Temporal and spatial distribution of the aquaporin 1 in spinal cord and dorsal root ganglia after traumatic injuries of the sciatic nerve.

PURPOSE: The aquaporin family comprises a large family of integral membrane proteins that enable the movement of water and other small, neutral solutes across plasma membranes. Although function and mechanism of aquaporins in central nervous system injury have been reported, the pathophysiologic role of aquaporin 1 (AQP1) in peripheral nerve has not been extensively documented. In the present study, we aimed to study the temporal and spatial distribution of AQP1 in spinal cord and dorsal root ganglia after sciatic nerve injury. METHODS: Forty-eight adult female mice were randomly divided into four groups (intact controls, sham operated, cut injury, and crush injury). Animals receiving cut or crush injuries were sacrificed at the 2nd, 24th, and 48th postoperative hours. Spinal cord samples at the level of lumbosacral intumescences and corresponding dorsal root ganglia on the experimental and contralateral side were dissected free and proceeded to AQP1 immunohistochemistry. RESULTS: Our quantitative estimations revealed that a sharp increase in AQP1 immunoreactivity at the 24th postoperative hour was observed. This sharp increase was no more evident at 48 h after sciatic nerve injury. Identical peak was observed after both cut and crush injuries. CONCLUSIONS: We demonstrated that there was a temporal relationship with an increased expression of AQP1 following injury sustained to the sciatic nerve that was significantly observed in dorsal root ganglia and spinal cord. Those expressions were also subsided over time.