F&S science · 2026
Follicle survival and oxidative stress in human ovarian tissue xenografts after oral antioxidant treatment: N-acetylcysteine and FERTILIX.
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Subiran Adrados Cristina, Olesen Hanna Ørnes, Olesen Sophie Vernimmen, Zeuthen Mette Christa, Pors Susanne Elisabeth, Pedersen Anette Tønnes, Kristensen Stine Gry
Аннотация
OBJECTIVE: To improve ovarian tissue transplantation effectiveness by limiting oxidative stress after transplantation, thus increasing follicle survival.
DESIGN: Experimental laboratory-controlled study. Immunodeficient mice were transplanted with frozen-thawed human ovarian cortex pieces, and received 7 days of oral treatment. The grafts were recovered 7 days and 4 weeks after transplantation.
SUBJECTS: A total of 2-4 ovarian tissue fragments per patient were donated by the patients (n = 26) undergoing ovarian tissue cryopreservation for fertility preservation and transplanted to immunodeficient mice.
EXPOSURE: Xenotransplanted mice received 7 days of oral treatment with either 150 mg/kg N-acetylcysteine (NAC) (NAC 150), 300 mg/kg NAC (NAC 300), FERTILIX, or Control (vehicle).
MAIN OUTCOME MEASURED: Follicle density 1 and 4 weeks after transplantation, malondialdehyde (MDA) immunohistochemistry assay and expression of antioxidant, mitochondrial, and apoptotic key genes.
RESULTS: After 7 days of transplantation, ovarian xenografts showed no significant differences in antioxidant genes (HMOX and CATALASE), mitochondrial stress genes (TFAM and HSP10), oxidative stress gene (ALDH3A2), BAX/BCL2 ratio, or malondialdehyde-positive areas (Control: 7.54% ± 2.23%; NAC 150: 4.99% ± 1.23%; NAC 300: 5.91% ± 1.19%; and FERTILIX: 10.30% ± 2.63%). However, follicle densities (follicles/mm3, mean ± SEM) showed a modest, nonsignificant increase in the NAC 150 (13.2 ± 2.85) and FERTILIX (20 ± 7.79) groups compared with controls (8.5 ± 2.85) after 4 weeks of grafting.
CONCLUSION: These findings suggest that orally administered FERTILIX and NAC have little to no efficacy in reducing oxidative stress or improving follicle survival in xenotransplanted human ovarian tissue.
DESIGN: Experimental laboratory-controlled study. Immunodeficient mice were transplanted with frozen-thawed human ovarian cortex pieces, and received 7 days of oral treatment. The grafts were recovered 7 days and 4 weeks after transplantation.
SUBJECTS: A total of 2-4 ovarian tissue fragments per patient were donated by the patients (n = 26) undergoing ovarian tissue cryopreservation for fertility preservation and transplanted to immunodeficient mice.
EXPOSURE: Xenotransplanted mice received 7 days of oral treatment with either 150 mg/kg N-acetylcysteine (NAC) (NAC 150), 300 mg/kg NAC (NAC 300), FERTILIX, or Control (vehicle).
MAIN OUTCOME MEASURED: Follicle density 1 and 4 weeks after transplantation, malondialdehyde (MDA) immunohistochemistry assay and expression of antioxidant, mitochondrial, and apoptotic key genes.
RESULTS: After 7 days of transplantation, ovarian xenografts showed no significant differences in antioxidant genes (HMOX and CATALASE), mitochondrial stress genes (TFAM and HSP10), oxidative stress gene (ALDH3A2), BAX/BCL2 ratio, or malondialdehyde-positive areas (Control: 7.54% ± 2.23%; NAC 150: 4.99% ± 1.23%; NAC 300: 5.91% ± 1.19%; and FERTILIX: 10.30% ± 2.63%). However, follicle densities (follicles/mm3, mean ± SEM) showed a modest, nonsignificant increase in the NAC 150 (13.2 ± 2.85) and FERTILIX (20 ± 7.79) groups compared with controls (8.5 ± 2.85) after 4 weeks of grafting.
CONCLUSION: These findings suggest that orally administered FERTILIX and NAC have little to no efficacy in reducing oxidative stress or improving follicle survival in xenotransplanted human ovarian tissue.