Search

Background Doxorubicin (DOX), is a chemotherapeutic agent, which evokes oxidative stress and cell apoptosis in testicular tissue. It is known that the activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP), leading to apoptosis induced by DOX. The aim of the present study is to investigate whether PARP pathway has a role in DOX-induced testicular damage and infertility utilizing pharmacological PARP-1 inhibitor, PJ34, and PARP-1 knockout mice model. Methods Firstly, we assessed the activation of PARP pathway after DOX-induction at various hours by immunohistochemistry and western blot analysis. Secondly, we evaluated the role of PARP pathway in DOX-induced testicular damage, sperm motility, and fertility with pharmacological inhibition of PARP by using PJ34. Finally, we aimed to correlate a functional relationship between PARP-1 and DOX using PARP-1 knockout mice in DOX-induced testicular damage. Doxorubicin levels in plasma and testis tissue were also assessed. Results In DOX-induced group; PARP-1, PAR and apoptotic pathway protein expressions, increased significantly. In DOX + PJ34 group; PAR, cytochrome c, and AIF levels decreased significantly. Testicular weights, sperm motility, and mean the number of pups per litter decreased in DOX-induced group after 28 days, however they were similar to the control group in DOX-PJ34 group. In PARP-1 KO group, seminiferous tubule morphology was impaired significantly after 28 days of DOX-administration. Conclusions Our study indicates that DOX-induced testicular damage may be related to over-activation of PARP-1. PJ34 application was effective in preventing severe testicular damage caused by DOX-injection and may be considered for fertility protection against DOX-induced testicular damage.

Usta, Akın (Balikesir Author), The effects of metformin on a testicular torsion injury in adolescent rat testis after I/R were evaluated in the present study. Forty adolescent rats were divided into five groups with eight rats per group: a control group; a sham-operated group; an ischaemia group, where torsion was applied for 4 hr and testis was examined immediately after detorsion; an I/R group, where torsion was applied for 4 hr and the testis was examined 4 hr after detorsion; and an I/R + M group, where the metformin (300 mg/kg) administration was added to the identical procedures used for the I/R group. Spermatogenesis, basal membrane integrity and cleaved caspase-3 expression were assessed. The I/R + M group had a significantly higher Johnsen score than the I/R group (7.9 +/- 0.1 vs. 7.5 +/- 0.2; p F-value = 14.2). Failure of basal membrane integrity was highest in the ischaemia group (45 +/- 5) compared to the other groups (control group, 20 +/- 5; sham-operated group, 16.6 +/- 2.8), but not different between the I/R + M (31.6 +/- 12.5) and the I/R groups (25 +/- 3.5). Cleaved caspase-3 expression was highest in the ischaemia group (73.5 +/- 0.7), and significantly lower in the I/R + M group (33.4 +/- 0.9) than the I/R group (58.5 +/- 0.2; p F-value = 7.6). Metformin decreases testicular damage by exerting protection against the harmful effects of I/R on spermatogenesis and alleviating apoptosis in adolescent rat testis.

Usta, Akın (Balikesir Author), Introduction: Poor semen quality is the main cause of male factor. The aim of this study was to evaluate the effect of sperm source on the outcome of intracytoplasmic sperm injection-embryo transfer cycles (ICSI-ET) in normoresponder women.Methods: A total of 884 normoresponder women, underwent first ICSI cycles were evaluated. Fertilization, cleavage, embryo morphology, clinical pregnancy, miscarriage and live birth rates were compared. Ejaculated semen samples were collected by masturbation. Sperm retrieval from the testis was performed percutaneously by microdissection testicular sperm extraction (m-TESE) under local anesthesia.Results: Patients were divided four group according to source of sperm and sperm parameters. Testicular spermatozoa obtained from men with azoospermia (group 1, n=43), severe oligoasthenoteratozoospermia (sOAT), (group 2, n=93), oligoasthenoteratozoospermia (OAT) (group 3, n=209) and normal semen analysis (group 4, n=539). The most reduced fertilization rate was observed with testicular spermatozoa and the fertilization rate increased as semen quality increased from Group 2 to 4. Our results indicated that semen quality can affect the fertilization process. We observed that the cleavage and high-quality embryo rates were highest in group I (88.4% and 93%, respectively) compared to other groups. Clinical outcomes of ICSI did not show statistically significant differences in the rates of clinical pregnancy, miscarriage and live birth rate.Conclusion: Neither sperm parameters nor the source of spermatozoa affects live birth rate in normoresponder women when motile/morphologically normal spermatozoa is present.

Usta, Akın (Balikesir Author), "Objectives: To compare the live birth rates and moderate/severe ovarian hyperstimulation syndrome (OHSS) rates of 2 different approaches using gonadotropin-releasing hormone (GnRH) agonist triggering in high responder women. Methods: A retrospective cohort study was performed to evaluate intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) outcomes in high responder women who underwent ovulation induction with a GnRH antagonist protocol between April 2011 and March 2015. In group 1 (n=74), GnRH agonist was used for ovulation triggering with the concomitant use of 1500 IU of urinary human chorionic gonadotropin (hCG) immediately after oocyte retrieval followed by fresh ET and standard luteal support. In group 2 (n=48), GnRH agonist was used for triggering after freezing all embryos and subsequent frozen/thawed embryo transfer (FET); this approach is considered the ""freeze-all"" approach. Results: Baseline characteristics were similar between the groups. The clinical pregnancy rates for group 1 was 45.9% and group 2 was 43.8% (p=0.812, chi-squared test) and live birth rates for group 1 was 40.5% and for group 2 41.7% (p=0.902, chi-squared test) were comparable between groups. In group 1, late-onset OHSS was observed (one severe case and one moderate case) in 2 patients (2.7%). In group 2, none of the patients experienced moderate/severe OHSS. Conclusion: The live birth rate with GnRH agonist triggering and concomitant use of 1500 IU of hCG immediately after oocyte retrieval was similar to that obtained with the freeze-all approach and FET in a subsequent cycle. The administration of a low dose of hCG in GnRH agonist trigger cycles caused moderate/severe OHSS in 2.7% of the patients."