Effect of exogenous GnRH at the time of artificial insemination on reproductive performance of awassi ewes synchronized with progestagen-PMSG-PGF2α combination

This study was carried out to investigate the efficacy of PGF2a for oestrus synchronization (ES) in Awassi ewes to which were administered the progestagen–PMSG combination, and to evaluate the effect of the exogenous GnRH administration immediately after the artificial insemination (AI) on their pregnancy rate and lambing performance during the breeding season. The ewes (n ¼ 33) were treated with an intravaginal sponge impregnated with 30 mg fluorogestane acetate for 12 days and were injected with 500 IU PMSG at the time of removal of the sponge. The ewes were then divided into three equal groups of 11 ewes each. One millilitre of physiological saline (0.9% NaCl; placebo) was administered to each ewe in Group 1 at the time of second AI. Approximately 4 lg GnRH (busereline) was injected to each ewe in Group 2 immediately after second AI. A total of 150 lg PGF2a (cloprostenole) was injected at the time of sponge removal on day 12 and 4 lg GnRH immediately after the second AI was also treated to each ewe in Group 3. Intracervical AI with diluted fresh semen was performed twice at 12 and 24 h following the onset of oestrus. The injection-oestrus onset and injection-oestrus-end interval in Group 3 was significantly (p < 0.001) shorter than both Groups 1 and 2. Although the pregnancy rates of Groups 2 and 3 (81.8%; 9/11) were numerically higher than of Group 1 (63.6%; 7/11), the difference among the groups was statistically insignificant. The multiple birth rate of Group 3 was found higher than Groups 1 and 2. However, the number of single lambs of Group 1 was also higher than Groups 2 and 3 (p < 0.05). Despite the litter sizes of Groups 2 (1.27; 14/11) and 3 (1.55; 17/11) being numerically higher than Group 1 (0.73; 8/11), the differences among all the groups were statistically insignificant. In conclusion, the administration of PGF2a at the time of removal of the sponge shortens the injection oestrus-onset and oestrus-end interval in Awassi ewes treated with progestagen–PMSG. Additionally, exogenous GnRH treatment immediately after the AI increases the multiple birth rate of Awassi ewes synchronized with progestagen– PMSG–PGF2a combination

Effect of pregnancy and foetal number on diameter of corpus luteum, maternal progesterone concentration and oxidant/antioxidant balance in ewes

The aim of this study was to determine the changes in diameter of corpus luteum (CL), maternal progesterone (P) concentration, lipid peroxidation and non-enzymatic antioxidant levels along with enzymatic antioxidant activities in pregnant ewes bearing single and twin foetuses. The ewes were selected from healthy animals that were brought to the abattoir for slaughtering. The ewes were divided into three groups: Group 1 (non-pregnant, non-oestrous, n = 30), Group 2 (pregnant bearing a single foetus, n = 30) and Group 3 (pregnant bearing twin foetuses, n = 12) after they were slaughtered. Pregnant ewes were in the first half of the pregnancy. The diameter of CL and P concentration of pregnant ewes bearing a single foetus or twin foetuses were found higher than that found in non-pregnant ewes. Similarly, the P concentration of pregnant ewes bearing twin foetuses was higher than that found in pregnant ewes bearing a single foetus. Malondialdehyde (MDA) level in pregnant ewes bearing twin foetuses was higher than that found in both non-pregnant and pregnant ewes bearing a single foetus. The serum glutathione (GSH) level and glutathione-peroxidase (GSH-Px) activity of pregnant ewes bearing twin foetuses were found lower than that found in non-pregnant ewes. Additionally, the GSH-Px activity of pregnant ewes bearing twin foetuses was found lower than that found in pregnant ewes bearing a single foetus. No significant difference was found between pregnant ewes bearing female and male foetus with respect to diameter of CL, P concentration and oxidative stress parameters. There were significant positive correlations between foetal number (0, 1, 2) and diameter of CL, P concentration, MDA level, and between P concentration and diameter of CL, MDA level. However, significant negative correlations were found between foetal number (0, 1, 2) and GSH level, GSH-Px activity, and between P concentration and GSH-Px activity. In conclusion, the diameter of CL enlarges, P production increases and oxidant ⁄ antioxidant balance impairs because of the gestation stress in ewes during pregnancy

Can taraxacum officinale (dandelion) extract be an alternative of paracetamol in inflammatory and painful cases? an evaluation with regard to biochemical and reproductive parameters

The aim of this study was to investigate the usage of Taraxacum officinale extract (TOE) in inflammatory and painful cases as an alternative to paracetamol (PRC) through the assessment of biochemical and reproductive parameters. Totally, 30 male Sprague Dawley rats aged eight weeks old, were used in this study. The animals were obtained from Atatürk University Experimental Research and Application Centre and kept under standard laboratory conditions. Commercial pellet chow and fresh drinking water were available ad libitum. Rats were divided into five groups: Group I (n= 6); referred as control. Group II (n=6); referred as TOE150 (150 mg/kg). Group III (n=6); referred as TOE200 (200 mg/kg). Group IV (n=6); referred as TOE250 (250 mg/kg). Group V (n=6); referred as Paracetamol (PRC) (2 g/kg). The treatment was performed for consecutive 8 days. The animals were tranquilized and sacrificed on 9th day of study. Blood samples, cauda epididymal semen samples and testes tissues were collected. Routine semen examinations were performed and oxidative stress levels of testicular tissues were assayed. Reproductive organ weights [total testes weight (TTW) and total cauda epididymal weights (TCEW)] were recorded. Motility in TOE250 group was significantly higher when compared to the other groups (P<0.05). Velocity of sperm cells in PRC group was significantly lower when compared to the other groups (P<0.05). Dead sperm rate in control group was significantly higher when compared to the other groups (P<0.001). On the other hand, the lowest TCEW was in TOE150 group (P<0.05). There were no differences in terms of TTW among all groups. Malondialdehyde (MDA) level of PRC group was significantly higher than the treatment groups (P<0.05). Besides, glutathione peroxidase (GPx) levels of PRC group were lower than the other groups (P<0.001). Superoxide dismutase (SOD) level of PRC group was significantly lower than the treatment groups (P<0.001). The lowest catalase (CAT) level was in PRC group and the highest glutathione (GSH) level was in T200 group (P<0.001). In conclusion, it was observed that TOE could use as alternative of PRC and hence can be avoided from negative effects of PRC on biochemical and reproductive parameters

Effects of pomegranate juice consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level in male rats

Background & aim: Pomegranate fruit is inescapably linked with fertility, birth and eternal life because of its many seeds. The aim of this study was to investigate the effects of pomegranate juice (PJ) consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level of male healthy rats. Methods: Twenty-eight healthy adult male Wistar rats were divided into four groups; each group containing seven rats. One milliliter distilled water, 0.25 mL PJ plus 0.75 mL distilled water, 0.50 mL PJ plus 0.50 mL distilled water and 1 mL PJ were given daily for seven weeks by gavage to rats in the first, second, third and fourth groups, respectively. Body and reproductive organ weights, spermatogenic cell density, sperm characteristics, levels of antioxidant vitamins, testosterone, and lipid peroxidation and, antioxidant enzyme activities were investigated. All analyses were done only once at the end of the seven week study period. Data were compared by analysis of variance (ANOVA) and the degree of significance was set at P < 0.05. Results: A significant decrease in malondialdehyde (MDA) level and marked increases in glutathione (GSH), glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and vitamin C level were observed in rats treated with different doses of PJ. PJ consumption provided an increase in epididymal sperm concentration, sperm motility, spermatogenic cell density and diameter of seminiferous tubules and germinal cell layer thickness, and it decreased abnormal sperm rate when compared to the control group. Conclusion: The results suggest that PJ consumption improves sperm quality and antioxidant activity of rats

PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma

Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma; DIPG), are uniformly fatal brain tumors that lack effective treatment. Analysis of CRISPR/Cas9 loss-of-function gene deletion screens identified PIK3CA and MTOR as targetable molecular dependencies across patient derived models of DIPG, highlighting the therapeutic potential of the blood-brain barrier–penetrant PI3K/Akt/mTOR inhibitor, paxalisib. At the human-equivalent maximum tolerated dose, mice treated with paxalisib experienced systemic glucose feedback and increased insulin levels commensurate with patients using PI3K inhibitors. To exploit genetic dependence and overcome resistance while maintaining compliance and therapeutic benefit, we combined paxalisib with the antihyperglycemic drug metformin. Metformin restored glucose homeostasis and decreased phosphorylation of the insulin receptor in vivo, a common mechanism of PI3K-inhibitor resistance, extending survival of orthotopic models. DIPG models treated with paxalisib increased calcium-activated PKC signaling. The brain penetrant PKC inhibitor enzastaurin, in combination with paxalisib, synergistically extended the survival of multiple orthotopic patient-derived and immunocompetent syngeneic allograft models; benefits potentiated in combination with metformin and standard-of-care radiotherapy. Therapeutic adaptation was assessed using spatial transcriptomics and ATAC-Seq, identifying changes in myelination and tumor immune microenvironment crosstalk. Collectively, this study has identified what we believe to be a clinically relevant DIPG therapeutic combinational strategy

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

Spermatozoon DNA'sı hasarı (DNA Damage of Sperm)

Sperm DNA damages have occured in the sperm DNA at different levels due to various in vivo and in vitro reasons. The damage of sperm DNA has been observed in human and many species of animals such as mice, horse, porcine and fish. These damages occured in sperm DNA are some structural damages such as degradation of chromatin structure, oxidation of DNA bases, false conjugation, obstruction of tubulin polimerisation, changing of bases chemically, abnormalities in the chromatin structure, cracking of DNA chain, crossing of DNA-DNA and DNA-protein, mutations in DNA. Simple cell gel electroforesis, tunel, the measurement of structure of sperm chromatin and 8-hydroxy 2-deoxyguanosine are used to determine these damages occured in sperm DNA. The damage in sperm DNA causes occuring of abnormal embriyonic development and infertility. Different in vivo and in vitro methods to prevent these damages were established. In this review the data regarding the structure of sperm DNA, biological situations leading to damage of sperm DNA, determination methods of certain abnormalities and different preventive methods are discussed