Sagar Chhabria1, Vaishnavi Takle1, Nripen Sharma1, Prashant Kharkar2,3, Kshama Pansare1, Anish Tripathi1, Ashish Tripathi1, Deepa Bhartiya4. 1. Epigeneres Biotech Pvt. Ltd., Sun Mill Compound, Ikon House, B-Block, Senapati Bapat Marg, Lower Parel, Mumbai, Maharashtra, 400013, India. 2. Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai, 400 019, India. 3. Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's NMIMS, Vile Parle (West), Mumbai, 400 056, India. 4. Epigeneres Biotech Pvt. Ltd., Sun Mill Compound, Ikon House, B-Block, Senapati Bapat Marg, Lower Parel, Mumbai, Maharashtra, 400013, India. deepa.bhartiya@epigeneres.com.
Abstract
BACKGROUND: Fertility preservation and restoration in cancer patients/survivors is the need of present times when increased numbers of patients get cured of cancer but face infertility as a serious side effect. Resveratrol has beneficial effects on chemoablated ovaries and testes in mice but has failed to enter the clinics because of extremely poor bioavailability. The present study was undertaken to evaluate the protective and curative effects of Extremely active Resveratrol (XAR™)- a nano-formulation of resveratrol with significantly improved bioavailability- on mouse ovary and testis after chemotherapy. Effects of XAR™ and FSH were compared on stimulation of follicle growth in adult mice ovaries. XAR™ (25 mg/kg) was administered for two days prior to chemotherapy to study the protective effects on the mouse gonads. XAR™ was also administered for 14 days post chemoablation to study the regenerative effects. Besides effect on numbers of primordial and growing follicles and spermatogenesis, the effect of XAR™ was also evaluated on the transcripts specific for ovarian/testicular stem/progenitor/germ cells, their proliferation, differentiation, meiosis, and the antioxidant indices. RESULTS: Similar to FSH, XAR™ increased the numbers of primordial follicles (PF) as well as growing follicles. It protected the gonads from the adverse effects of chemotherapy and showed the ability to regenerate non-functional, chemoablated gonads. Besides stimulating follicle growth in adult ovaries similar to FSH, XAR™ also protected the testes from the adverse effects of chemotherapy and improved spermatogenesis. This was accompanied by improved anti-oxidant indices. CONCLUSIONS: The results of the present study potentiate the use of XAR™ in pilot clinical studies to protect gonadal function during oncotherapy and also regenerate non-functional gonads in cancer survivors by improving antioxidant indices and stem cell-based tissue regeneration.
BACKGROUND: Fertility preservation and restoration in cancer patients/survivors is the need of present times when increased numbers of patients get cured of cancer but face infertility as a serious side effect. Resveratrol has beneficial effects on chemoablated ovaries and testes in mice but has failed to enter the clinics because of extremely poor bioavailability. The present study was undertaken to evaluate the protective and curative effects of Extremely active Resveratrol (XAR™)- a nano-formulation of resveratrol with significantly improved bioavailability- on mouse ovary and testis after chemotherapy. Effects of XAR™ and FSH were compared on stimulation of follicle growth in adult mice ovaries. XAR™ (25 mg/kg) was administered for two days prior to chemotherapy to study the protective effects on the mouse gonads. XAR™ was also administered for 14 days post chemoablation to study the regenerative effects. Besides effect on numbers of primordial and growing follicles and spermatogenesis, the effect of XAR™ was also evaluated on the transcripts specific for ovarian/testicular stem/progenitor/germ cells, their proliferation, differentiation, meiosis, and the antioxidant indices. RESULTS: Similar to FSH, XAR™ increased the numbers of primordial follicles (PF) as well as growing follicles. It protected the gonads from the adverse effects of chemotherapy and showed the ability to regenerate non-functional, chemoablated gonads. Besides stimulating follicle growth in adult ovaries similar to FSH, XAR™ also protected the testes from the adverse effects of chemotherapy and improved spermatogenesis. This was accompanied by improved anti-oxidant indices. CONCLUSIONS: The results of the present study potentiate the use of XAR™ in pilot clinical studies to protect gonadal function during oncotherapy and also regenerate non-functional gonads in cancer survivors by improving antioxidant indices and stem cell-based tissue regeneration.