N-acetylcysteine improves function and follicular survival in mice ovarian grafts through inhibition of oxidative stress.

The effect of N-acetylcysteine (NAC) on mouse ovary heterotopic autotransplantation was investigated. Mice (age 4-5 weeks) were divided into the following groups: control; autograft plus NAC (150 mg/kg daily intraperitoneal injection) and autograft plus saline (n = 6 per group). Groups were treated from 1 day before until 7 days after transplantation. After 28 days, ovary compartments were estimated stereologically. Plasma malondialdehyde, progesterone, oestradiol concentrations and the percentage of apoptotic follicles were measured to evaluate the rate of oxidative stress and ovarian graft function. The mean total volume of ovary, cortex and the number of follicles was significantly higher (all P < 0.001) in the autografts plus NAC group compared with the saline group. In the autografts plus NAC group, the mean percentage of apoptotic follicles (P < 0.001) and malondialdehyde concentration (P < 0.001 day 7; P < 0.05 day 28) were significantly lower, whereas oestradiol concentration was significantly higher (P < 0.05) compared with the saline group. Although NAC cannot compensate the above parameters to the control level, it considerably improves follicular survival and development and also the structure and function of transplanted ovaries, through reducing oxidative stress and apoptosis.

Effects of erythropoietin on ischemia, follicular survival, and ovarian function in ovarian grafts.

Ovarian tissue transplantation is performed to preserve fertility in patients undergoing chemotherapy and radiotherapy. However, ischemia/reperfusion (IR) injury and free radical production occurring during the revascularization of the transplanted tissue are the major limitations of this procedure. The aim of this study was to investigate the effect of erythropoietin (EPO) as an antioxidant on oxidative stress and ovary survival following transplantation. The Naval Medical Research Institute (NMRI) mice (4-5 weeks old) were divided into three groups (six mice per group): control; autograft+saline, and autograft+EPO (500  IU/kg i.p.). After 28 days, ovary compartments were estimated stereologically. DNA fragmentation and plasma malondialdehyde (MDA), progesterone, and estradiol (E2) concentrations were also evaluated. The results were analyzed using one-way ANOVA and Tukey's test, and the means were significantly different at P<0.05. The mean total volume of ovary, cortex, and medulla and the number of follicles increased significantly in the autograft+EPO group (P<0.01). Apoptosis rate in the autograft+EPO group was lower than that in the autograft+saline group. The concentration of MDA decreased significantly in the autografted EPO-treated group than in the autografted saline-treated group (P<0.01). The concentration of E2 increased significantly in the autograft+EPO group than in the autograft+saline group (P<0.01). EPO reduced IR injury, increasing follicle survival and function in grafted ovaries. Free Persian abstract A Persian (Farsi) translation of the abstract is freely available online at http://www.reproduction-online.org/content/147/5/733/suppl/DC1.

Heterotopic autotransplantation of vitrified mouse ovary.

Purpose: The aim of this study was to investigate the survival and development of premature follicles and oocytes from a vitrified-transplanted ovary in a murine experimental model. Methods: The 14-day-old mice were unilaterally ovariectomized and the separated ovaries were vitrified by cryotop. After 2 weeks the ovaries were warmed and autotransplanted into the gluteus superfiscialis muscle. After 3 weeks, these ovaries (vit-trans), the ovaries from the opposite side (OPP), and 7-week fresh mouse ovaries as sham and control group (7 week-fresh), were recovered and examined histologically and by TUNEL test. Results: All 4 vitrified-autotransplanted ovaries had developing follicles. Primordial, primary, preantral and antral follicles were found in all three groups (7 week-fresh, OPP and vit-trans). The rate of apoptosis by TUNEL test was similar in all groups and no significant difference was found between vitrified-transplanted ovarian tissue and controls. Conclusions: These data demonstrate successful autotransplantation of vitrified whole mouse ovaries, manifested by the presence of all stages of folliculogenesis. According to the results of this experiment, heterotopic autotransplantation of whole cryopreserved ovary provides the opportunity for follicle development at all stages. However, further experiments are required to improve the efficiency of autotransplantation of cryopreserved ovaries to obtain better results.