Application of fibrin-based biomaterial for human ovarian tissue encapsulation and cryopreservation as alternative approach for fertility preservation.

This study aimed to investigate the effects of fibrin-based hydrogel encapsulation, with or without vascular endothelial growth factor (VEGF), on follicle quality and cell survival signaling pathways after ovarian tissue cryopreservation. Ovarian cortex donated by seven patients (ages 44-47 years old) was divided into four groups: I) fresh control, II) ovarian tissue without encapsulation (non-FT), III) fibrin (10 mg/mL fibrinogen plus 50 IU/mL thrombin; 10FT) encapsulated tissue without VEGF, and IV) encapsulated tissue with 0.1 µg/mL VEGF (10FT-VEGF), followed by a slow freezing process. Evaluation criteria included normal follicle morphology, density, cell proliferation, apoptosis, and metabolism signaling pathways (BAX/BCL-2 ratio, CASPASE-3 and 9, ATP-6 genes, VEGF-A, and ERK-1/2 protein expression levels). Major outcomes revealed that the percentages of morphologically normal follicles and density were significantly decreased by cryopreservation. Ovarian tissue encapsulation using the 10FT formulation (with or without VEGF) could maintain the ERK-signaling cascade, which was comparable to the fresh control. Among the frozen-thawed cohorts, the BAX/BCL-2 ratio, CASPASE-3, CASPASE-9, and ATP-6 expression levels were unfavorable in the non-FT group. However, statistically different results, including VEGF-A expression levels, were not detected. Collectively, our present data demonstrated the first applicable biomaterial matrix for human ovarian tissue encapsulation which might create an optimal intra-ovarian cortex environment during cryopreservation. Further studies to optimize hydrogel polymerization should be expanded, given the potential benefits for cancer patients who wish to preserve fertility through ovarian tissue cryopreservation.

Alu hypomethylation in naturally and surgically postmenopausal women; a cross-sectional study.

Menopause, which may accelerate the hallmarks of the natural aging process, represents a point in time characterized by the permanent cessation of menstruation following the loss of ovarian estrogen production. Unlike natural menopause, which is characterized by a gradual decrease in estrogen production, when both ovaries are removed before the natural age of menopause, the onset of estrogen deprivation is abrupt. Further, a decrease in genome methylation frequently occurs in aging cells, and the major interspersed repetitive DNA elements in humans are Alu elements. In blood cells, Alu demethylation starts at an age of approximately 40 years, and increases with age. Here, we explored the Alu methylation levels corresponding to age-matched pre-menopausal, naturally postmenopausal, and surgically postmenopausal women aged 45-55 years (n = 60 in each group). Our results indicated that the body mass index (BMI), time-since-menopause, and Alu methylation levels corresponding to the three groups were significantly different. However, no correlations between Alu methylation level and BMI, time-since-menopause, or age were observed. Additionally, the Alu methylation level corresponding to the natural post-menopause group was significantly lower those corresponding to the pre-menopausal (p = 0.001) and surgical post-menopausal (p = 0.037) groups. In conclusion, Alu hypomethylation occurs in naturally postmenopausal women, implying that when women reach the age of natural menopause, the cell aging process may progress significantly with genome hypomethylation. These findings, notwithstanding, further studies are necessary to clarify whether bilateral oophorectomy before the age of menopause affects the cell aging process to a greater extent than natural menopause, and whether estrogen therapy or other interventions can delay cell aging in this regard.