Ye Min, Shan Yiran, Lu Bingchuan, Luo Hao, Li Binhan, Zhang Yanmei, Wang Zixuan, Guo Yuzhi, Ouyang Liliang, Gu Jin, Xiong Zhuo, Zhang Ting
Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.
Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, 100084, China.
Bioact Mater. 2023 Mar 7;26:216-230. doi: 10.1016/j.bioactmat.2023.02.029. eCollection 2023 Aug.
The bio-engineered ovary is an essential technology for treating female infertility. Especially the development of relevant models could be a critical step in a drug study. Herein, we develop a semi-opened culturing system (SOCS) strategy that maintains a 3D structure of follicles during the culture. Based on the SOCS, we further developed micro-cavity ovary (MCO) with mouse follicles by the microsphere-templated technique, where sacrificial gelatin microspheres were mixed with photo-crosslinkable gelatin methacryloyl (GelMA) to engineer a micro-cavity niche for follicle growth. The semi-opened MCO could support the follicle growing to the antral stage, secreting hormones, and ovulating cumulus-oocyte complex out of the MCO without extra manipulation. The MCO-ovulated oocyte exhibits a highly similar transcriptome to the counterpart (correlation of 0.97) and can be fertilized. Moreover, we found that a high ROS level could affect the cumulus expansion, which may result in anovulation disorder. The damage could be rescued by melatonin, but the end of cumulus expansion was 3h earlier than anticipation, validating that MCO has the potential for investigating ovarian toxic agents . We provide a novel approach for building an ovarian model to recapitulate ovarian functions and test chemical toxicity, suggesting it has the potential for clinical research in the future.
生物工程卵巢是治疗女性不孕症的一项关键技术。尤其是相关模型的开发可能是药物研究中的关键一步。在此，我们开发了一种半开放式培养系统（SOCS）策略，该策略在培养过程中维持卵泡的三维结构。基于SOCS，我们通过微球模板技术进一步构建了带有小鼠卵泡的微腔卵巢（MCO），其中将牺牲性明胶微球与可光交联的甲基丙烯酰化明胶（GelMA）混合，以构建用于卵泡生长的微腔龛。半开放式MCO能够支持卵泡生长至窦状卵泡阶段，分泌激素，并在无需额外操作的情况下使卵丘 - 卵母细胞复合体从MCO中排出并排卵。MCO排卵的卵母细胞表现出与对照卵母细胞高度相似的转录组（相关性为0.97），并且能够受精。此外，我们发现高活性氧水平会影响卵丘扩展，这可能导致排卵障碍。褪黑素可以挽救这种损伤，但卵丘扩展的结束时间比预期早3小时，这证实了MCO具有研究卵巢毒性药物的潜力。我们提供了一种构建卵巢模型以重现卵巢功能并测试化学毒性的新方法，表明其未来具有临床研究的潜力。
