The effects of human amnion membrane-derived mesenchymal stem cells conditioned medium on ionizing radiation-induced premature ovarian failure and endoplasmic reticulum stress-related apoptosis mechanism.

OBJECTIVES: Premature ovarian failure (POF) is defined as the cessation of menstrual periods for at least 4-6 months before the age of 40 years, accompanied by FSH values measuring over 40 IU/L for a month. Radiation therapy, one of the cancer treatment methods, is known to accelerate ovarian aging by reducing and eliminating the number of primordial follicles in the ovarian follicle pool. Ionizing radiation has been reported to cause POF. The objective of this study is to investigate the impact of mesenchymal stem cell conditioned medium (hAMSCs-CM), which is isolated from the amniotic membrane of human placenta, on premature ovarian failure (POF) caused by whole-body irradiation. The study will focus on the ER stress and apoptosis mechanisms in the process. STUDY DISAYN: A POF model was created by exposing rats to 7 Gy of whole-body irradiation. Serum-free hAMSCs-CM were then administered via the tail vein. Follicle count was performed on the ovaries, and immunohistochemistry was used to determine the expressions of GRP78, CHOP, IRE-1, caspase-12, caspase-9, caspase-3. TUNEL was also carried out, and levels of serum FSH, LH, E2, AMH, and oxidative stress marker 8-OHdG were measured. RESULTS AND CONCLUSION: The application of hAMSCs-CM has been found to have a positive impact on follicles affected by radiation. After treatment, the number of primordial, primary, secondary, and graafian follicles, which had previously decreased due to radiation, showed an increase. Furthermore, the number of atretic follicles, which had been increasing due to radiation, showed a decrease. ER is one of the targets affected by ionizing radiation. After ionizing radiation, the expressions of ER stress-related markers and apoptosis markers increased in the ovary. After hAMSCs-CM administration, the expressions of these markers and number of TUNEL-positive cells decreased. Following irradiation, anti-mullerian hormone (AMH) and estradiol (E2) levels decreased, while follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels increased. After administration of hAMSCs-CM, AMH and E2 levels increased, while FSH and LH levels decreased. Amnion membrane-derived mesenchymal stem cell conditioned medium can play a therapeutic role in ionizing radiation-induced premature ovarian failure by reducing endoplasmic reticulum stress and apoptosis.

Human Amnion Membrane-Derived Mesenchymal Stem Cells and Conditioned Medium Can Ameliorate X-Irradiation-Induced Testicular Injury by Reducing Endoplasmic Reticulum Stress and Apoptosis.

Today, infertility affects 15% of couples and half of this rate is due to reproductive problems in men. Radiation-induced damage to the testicles causes sterility depending on the dose. Radiation causes endoplasmic reticulum (ER) stress and ER stress induces apoptosis. In this study, the effect of human amniotic membrane-derived mesenchymal stem cells (hAMSCs) and conditioned medium (hAMSCs-CM) on testicular damage induced by ionizing radiation is aimed to be elucidated through ER stress and apoptosis mechanisms. Six gray scrotal irradiation was used to create a testicular injury model. hAMSCs isolated and characterized with immunofluorescence and flow cytometry, while 2.5 × 105 hAMSCs were transplanted into testis and hAMSCs-CM was applied. Fertility assessment was performed. Expressions of ER stress markers GRP78, Ire1, Chop and Caspase-12, and Caspase-3 were determined. TUNEL was performed. Serum FSH, LH, and testosterone were measured. After hAMSC transplantation and administration of hAMSCs-CM, offsprings were obtained. Seminiferous tubule diameter and seminiferous epithelial height increased. The expression of GRP78, IRE1α, CHOP, Caspase-12, and Caspase-3 decreased. Percentages of tunel positive cells decreased. While FSH and LH levels decreased, testosterone increased. After irradiation, both hAMSCs transplantation and paracrine activity of hAMSCs may have a role in reducing ER stress by suppressing the UPR response. Decrease in FSH and LH and increase in testosterone level after MSCs transplantation may have contributed to the improvement of spermatogenesis. Thus, it can be said that MSCs derived from human amniotic membrane can improve ionized radiation-induced testicular damage by reducing ER stress and apoptosis.

Vascular effect of levonorgestrel intrauterine system on heavy menstrual bleeding: is it associated with hemodynamic changes in uterine, radial, and spiral arteries?

The aim of this study was to evaluate the clinical and blood flow changes associated with the use of a levonorgestrel-releasing intrauterine device (LNG-IUD) in patients with idiopathic heavy menstrual bleeding (HMB). LNG-IUD was inserted into a total of 91 patients (39.5 ± 5.4 years) who were diagnosed with HMB. Uterine volume, ovarian volume, uterine, radial and spiral artery blood flow, Pictorial Blood Loss Assessment Chart (PBAC) scores, and other clinical and laboratory parameters were evaluated before and 12 months after insertion of LNG-IUD. Compared to pre-insertion values, LNG-IUD dramatically improved haemoglobin, PBAC scores, and endometrial thickness. Mean resistance indices of radial and spiral arteries significantly increased 12 months after insertion. Our study results suggest that a significant increase in the resistance indices of the intra-myometrial arteries in LNG-IUD users one year after insertion may be due to its local progestational effects, indicating a possible mechanism of LNG-IUD in reducing menstrual blood flow.Impact StatementsWhat is already known on this subject? The mechanisms of action of LNG-IUD on heavy menstrual bleeding include atrophy, decidualization and vascular changes of in the endometrium, resulting endometrial suppression. However, the exact mechanism to stop bleeding is not clear.What do the results of this study add? The present study suggests that one of the effects of the LNG-IUD on heavy menstrual bleeding is its ability to increase the resistance indexes of the intra-myometrial arteries.What are the implications of these findings for clinical practice and/or further research? These results will foster further studies on the effects of LNG-IUD on intra-myometrial arteries and will further assure clinicians on the vascular effect of LNG-IUD during management of heavy menstrual bleeding which includes hysterectomy as a final step.

Evaluation of uterine artery recanalization and doppler parameters after bilateral uterine artery ligation in women with postpartum hemorrhage.

AIM: The evaluation of the uterine artery recanalization rate and color Doppler parameters during follow-up after bilateral uterine artery ligation (BUAL) for postpartum hemorrhage (PPH) related to uterine atony. MATERIAL AND METHOD: A total of 40 female patients who underwent BUAL for PPH related to uterine atony and 96 females who gave birth without complication at Hatay Obstetrics and Gynecology Hospital between January 2009 and December 2012 (48 months) were included in the study. The patients' uterine artery recanalization rate and all subjects' color Doppler ultrasonographic parameters (PI, RI, PSV and EDV) were evaluated at the 6th and 12(th) months. RESULT: No statistically significant difference was found between the age, obstetric history (gravida and parity), BMI, type of delivery, birth weight and gestational age when the demographic data of the groups were evaluated. The patient group UtA recanalization rate was 32.5% and 37.5% for the left and right UtA respectively at the 12-month follow-up. No statistically significant difference was found in the comparison of 6- and 12-month right and left uterine artery diameters and color doppler parameters of the patient group (UtA diameters P=0.322 and P=0.787, RI index P=0.390 and P=0.094, PI index P=0.949 and P=0.374, PSV P=0.335 and P=0.085, EDV P=0.173 and P=0.418, respectively). However, right and left ovarian volume was found to significantly increase during follow-up in patient group (P<0.001 for both right and left ovary). On the other hand, a statistically significant difference was found between the patient group and the control group in the comparison of the 6- and 12-month right and left uterine artery values (6th month; P<0.001 for both UtA diameters, RI, PI, PSV, EDV; 12(th) month; P<0.001 for right UtA diameter, RI, PI, PSV, EDV and P=0.002 for left UtA diameter). A statistically significant difference was found only in right ovary volume in the 6th month evaluation of the patient and control group ovary volumes (P=0.011). DISCUSSION: The recanalization rate and isolated uterine blood supply during low-term follow-up are low following the BUAL technique. The evaluation of future fertility results will be helpful in determining the reliability of this procedure in a definite manner.

Can the ductus venosus doppler predict the hemoglobinopathies?

OBJECTIVE: The aim of our study was to investigate the ductus venosus doppler between 11-13+6 (week-day) in pregnant women with hemoglobinopaties and its relation with fetal outcomes. MATERIAL AND METHODS: A total of 100 pregnant women with hemoglobinopathies and 100 healthy pregnant women were included in our study. Ultrasonography (USG) was performed to all pregnant women and the ductus venosus doppler (DVD) flows were evaluated. The results were statistically analyzed. RESULTS: The mean hemoglobin level was significantly lower in hemoglobinopathy group (9.7 ± 0.7) than control group (10.67 ± 0.82) (P<0.001). There was a significant relationship between Vmax, Vmin, S/D and reverse 'a' wave in fetuses with hemoglobinopathies. Vmax, Vmin and S/D parameters were higher in the group of hemoglobinopathies (respectively mean value, 31.3 ± 1.66, 8.90 ± 0.81, 2.97 ± 0.49). Reverse 'a' wave was detected especially in all fetuses with sickle cell anemia. There was no significantly relationship between the groups in terms of PI, RI and HR. In a logistic regression analyses, fetal hemoglobinopathy was independently associated with Vmin (ß = 1.07, P = 0.001), S/D (ß = 2.61, P = 0.001) and reverse 'a' wave (ß = 2.46, P = 0.004). CONCLUSION: Pregnant women with hemoglobinopathies had changed ductus venosus doppler values in compared to normal pregnant women. Maternal anemia may cause this doppler changes. Furthermore all fetuses with sickle cell anemia (n = 5) had abnormal ductus venosus doppler findings. Further studies are needed to investigate the relationship between abnormal ductus venosus doppler findings and fetuses diagnosed with sickle cell anemia.

Evaluation of Mean Platelet Volume values in lean women with polycystic ovary syndrome.

OBJECTIVE: Mean Platelet Volume (MPV) is an important indicator of platelet activation. It is known that MPV increases in patients with coronory artery disease, diabetes mellitus, atherosclerosis and Polycystic ovary syndrome (PCOS). Our aim was to measure the MPV in lean patients with polycystic ovary syndrome. METHODS: The present study was designed to examine the platelet function by measuring MPV in non-obese women with PCOS. A total of 50 outpatients with PCOS were included. The control group consisted of 50 healthy subjects. Serum platelet, MPV, and white blood cell (WBC) levels were compared and evaluated retrospectively in all participants. These values were compared by statistical analysis. RESULTS: There were no statistically significant difference in between groups regarding MPV (p═0.357), WBC (p═0,414) and platelet (p═0,666). CONCLUSION: There are studies implying MPV increase in PCOS patients, in our patients MPV levels did not correlate with PCOS except for patients with obesity. We think that PCOS itself has no effect on MPV levels and obesity changes MPV levels.

Complications and outcomes of repeat cesarean section in adolescent women.

AIM: The evaluation of the effect of repeat cesarean sections in adolescent pregnancies on the morbidity, obstetric and perinatal results. MATERIALS AND METHODS: We reviewed the patient file and hospital records of patients who underwent at least one cesarean section among adolescent age group pregnant women who gave birth at our clinic between January 2010 and May 2013. The patients were divided into two groups as the patients who underwent the second cesarean section (116 patients) and those who underwent the third cesarean section (36 patients). The demographic data, maternal data and obstetric and perinatal results of the patients were evaluated. RESULTS: A significant difference was present between the patients in the evaluation of the total number of examinations during pregnancy (P = 0.001), total maternal weight gain during pregnancy (P = 0.006), and the first examination gestational age (P = 0.006) and all values were less favorable in the third cesarean group. The gestational week at birth (P < 0.001), birth weight (P < 0.001), and APGAR score (P < 0.001) in the group with the third cesarean section were statistically significantly lower than the second cesarean section. The third cesarean cesarean was found to cause a significant risk increase for placenta accreta risk in adolescent pregnancies (P = 0.042). CONCLUSION: The increasing number of cesarean sections in the adolescent group is seen to be a significant risk factor for low gestational week of birth, low birth weight and related morbidities. The most important reason for the increased morbidity with increasing cesarean sections in the adolescent age has been defined as placenta accreta.