Follicular development of fetal gonads under the skin of adult mice

Abstract

Adult ovarian tissues or biopsies isolated from patients prior to chemotherapy or irradiation can reconstitute ovarian functions when transplanted either in the abdomen or subcutaneously. Subcutaneously transplantation avoids invasive surgery and potential risks associated with internal procedures. We investigated whether functional ovaries could develop subcutaneously from early E12.5 fetal gonads without entering meiosis in mouse model. Unexpectedly, the subcutaneously transplanted fetal gonads failed to undergo folliculogenesis in the recipient mice. The transplanted gonads experienced meiotic deficiency and exhibited significant defects in DNA repair and recombination, increased apoptosis levels. Meiotic defects in the subcutaneous grafts were partly attributable to variations in temperature and oxygen concentration. However, completion of meiotic prophase I was effectively achieved through in vitro culture of the gonads at 37℃. Subsequently, the in vitro cultured E12.5 gonads, following subcutaneous transplantation, became competent in folliculogenesis, restoring endocrine functions. This finding may have implications for rejuvenating ovarioids from fetal gonad-like cells using pluripotent stem cell technologies, as well as for enhancing endocrine recovery and health span.

Keywords

follicle development / meiosis / gonad / ovary / subcutaneous transplantation

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The Author(s). Published by Oxford University Press on behalf of Higher Education Press.