Celik, Onder; Ak, Mehmet; Sahin, Erdem; Senturk, Senol; Ugur, Kader; Celik, Sudenaz; Celik, Nilufer; Cengiz, Ferhat; Muderris, Iptisam Ipek; Capar, Metin

The specialized resident-stem cells in gonads are tasked with restorating damaged ovarian cells following injury to maintain sequential reproductive events. When we talk about premature ovarian insufficiency (POI) we accept the existence of decreased stem cell and their regenerative abilities. The present study was to explain how restorating damaged ovarian cells following injury to maintain sequential reproductive events in evidence-based medicine indexed in PubMed and Web of Science. The exact mechanism is unclear stem cells transfer may improve compromised ovarian function and fertility outcome in women with POI. Soluble factors secreted by stem cell may rescue impaired mitochondrial function in oogonial stem cells, enhance metabolic capacity of resident stem cells, induce local neovascularization in the ovary, and activate gene shifting between transferred stem cells and germ cell precursors. This review may provide insight into how stem cells show some of their beneficial effects on compromised ovarian microenvironment and germ cell niche and paves the way for clinical trials for improving ovarian function of women with POI. We also had the opportunity to share our hypothesis about the design and development of induced oogonial stem cell (iOSC) and its use in POI.

Celik, Onder; Celik, Nilufer; Ugur, Kader; Hatirnaz, Safak; Celik, Sudenaz; Muderris, Iptisam Ipek; Yavuzkir, Seyda; Sahin, İbrahim; Yardim, Meltem; Aydin, Suleyman

The follicle must fulfill the following criteria if it is to survive the period between early embryonic life and the luteinizing hormone (LH) peak. It should (i) be surrounded by pregranulosa cells; (ii) complete the first meiotic division and become dormant; and (iii) continue metabolism during the dormant stage. Interaction between the natriuretic peptide precursor type C (Nppc) and its receptor, natriuretic peptide receptor 2 (Npr2), affects female fertility through the production of oocytes with developmental capacity and maintain oocyte meiotic arrest. While Nppc is expressed in mural cells, cumulus cells express Npr2. Nppc/ Npr2 system exerts its biological function on developing follicles by increasing the production of intracellular cyclic guanosine monophosphate (cGMP). This pathway not only contributes to the development of ovary and the uterus, but aids the formation of healthy eggs in terms of their morphological and genetic aspects. A defect in this pathway leads to asmall ovarian size, string-like uterine horns, and thin endometrium and myometrium. Disorganized chromosomes, abnormal cumulus expansion and early meiotic resumption occur in animals with defective Nppc/Npr2 signaling. The types and number of oocytes also decrease when there is incompetent Nppc/Npr2 signaling. This paper extends on most recent and relevant experimental evidence regarding Nppc/Npr2/cGMP signaling with regard to its crucial role in maintaining oocyte meiotic arrest and the production of oocytes with developmental capacity. We further discuss whether the agonist or antagonist forms of the members of this exciting pathway can be usedfor triggering final oocyte maturation.

Celik, Nilufer; Aydin, Suleyman; Ugur, Kader; Yardim, Meltem; Acet, Mustafa; Yavuzkir, Seyda; Sahin, İbrahim; Celik, Onder

This study was planned to test whether follicular fluid (FF) levels of patatin-like phospholipase domain containing 3-gene (PNPLA3:adiponutrin), preptin, kisspeptin, and amylin change in polycystic ovarian syndrome (PCOS). A total of 40 infertile volunteers undergoing IVF/ICSI were included in the study. They were divided into two groups as PCOS (n=20) and control group without PCOS (n=20). The controls were recruited from subjects with a poor ovarian response. The PCOS and control participants were matched according to their body mass index (BMI). Each group of participants underwent ovarian stimulation with GnRH antagonist protocol. Blood and FF samples of one dominant follicle were obtained from each subject during the oocyte pick-up. FF and serum levels of PNPLA3, preptin, kisspeptin and amylin were measured through ELISA. Amylin and adiponutrin median values were not different according to study groups (p>0.05). FF-preptin median values in the control group were similar to the serum preptin values of control and PCOS groups (Z=0.970, p=1.000 and Z=2.631, p=0.051, respectively). Medians of the serum preptin in control and PCOS groups were the same (Z=1.649; p=0.595). FF-preptin median values of PCOS group were significantly lower than the preptin median values of the control group. Serum preptin levels were positively correlated with HOMA-IR, but not with pregnancy rates and the number of retrieved oocytes. Serum kisspeptin levels were negatively correlated with the number of retrieved oocytes and pregnancy rates. While amylin and adiponutrin have no role in the folliculogenesis, kisspeptin and preptin work together for regulating follicle developmental capacity in PCOS.

Yalcin, Alper; Yumrutas, Onder; Kuloglu, Tuncay; Elibol, Ebru; Parlar, Ali; Yilmaz, Ismet; Pehlivan, Mustafa; Dogukan, Mevlut; Uckardes, Fatih; Aydin, Hasan

The present study was designed to determine the possible hepatoprotective effects of Salvia cryptantha (black weed) plant extract against carbon tetrachloride (CCl4)-induced hepatic injury in rats. Animals were grouped as follows: control group (Group I), CCl4 group (Group II), olive oil group (Group III), CCl4 + S. cryphantha 200 mg/kg group (Group IV), and CCl4 + S. cryptantha 400mg/kg group (Group V). Rats were injected intraperitoneally with CCl4 diluted in olive oil (50% v/v) at a dose of 1ml/kg body weight. Bax and Caspase3 were determined by immunohistochemical staining, while apoptotic index was evaluated using TUNEL assay. Total mRNA was isolated from liver tissues, and the levels of BCL2, Caspase3, SOD, CAT, and glutathione peroxidase (GPx) were determined by using PCR, while MDA level were determined using a colorimetric assay. The antioxidant and anti-apoptotic gene transcripts were decreased in all of the control and treatment groups, while Caspase3 levels were not statistically different. The S. cryptantha plant extract treatment was also found to improve SOD, GPx, and catalase levels, while reducing the serum levels of MDA. The extract of S. cryptantha supplementation had a protective effect against CCl4-induced liver damage. S. cryptantha extract as a supplement may be useful as a hepato-protective agent to combat the toxic effects caused by CCl4 and other chemicals.