Chen Jiyu, Liu Chang, Yu Yongqin, Ye Xiaoying, Liu Lin, Zhu Zhengmao
Department of Genetics and Cell Biology, College of Life Science, Nankai University, Tianjin 300071, China.
State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, China.
Life Med. 2025 Feb 24;4(3):lnaf007. doi: 10.1093/lifemedi/lnaf007. eCollection 2025 Jun.
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 culture of the gonads at 37°C. Subsequently, the 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.
从化疗或放疗前的患者身上分离出的成人卵巢组织或活检样本,在腹部或皮下移植时可恢复卵巢功能。皮下移植避免了侵入性手术以及与内部手术相关的潜在风险。我们在小鼠模型中研究了早期E12.5胎儿性腺能否在皮下发育出功能正常的卵巢而不进入减数分裂。出乎意料的是,皮下移植的胎儿性腺在受体小鼠中未能发生卵泡生成。移植的性腺出现减数分裂缺陷,在DNA修复和重组方面表现出明显缺陷,细胞凋亡水平增加。皮下移植物中的减数分裂缺陷部分归因于温度和氧气浓度的变化。然而,通过在37°C培养性腺有效地完成了减数分裂前期I。随后,培养后的E12.5性腺在皮下移植后能够进行卵泡生成,恢复内分泌功能。这一发现可能对利用多能干细胞技术使胎儿性腺样细胞的类卵巢恢复活力以及增强内分泌恢复和健康寿命具有启示意义。