Autonomous follicle growth and the production of mature human eggs in vitro: with or without the ovary?
Autonomous follicle growth and the production of mature human eggs in vitro: with or without the ovary?
复制标题
卵泡自主生长和体外成熟卵子的产生：有或没有卵巢？
DOI：
10.1093/humrep/deab052
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Duncan,FrancescaElizabeth
中科院分区：
文献类型：
--
作者：
Kristensen,StineGry;Duncan,FrancescaElizabeth
One of the most remarkable features of the ovarian follicle is its ability to support key aspects of oogenesis and folliculogenesis upon isolation from the ovary and growth ex vivo. Follicles grown in various culture systems have the capacity to survive and grow, support oocyte growth and granulosa cell proliferation and differentiation, produce and secrete hormones, respond to ovulatory cues, and produce mature gametes (Simon et al., 2020). Culture of ovarian follicles is an important model system for studying fundamental biology but also has potential application in clinical fertility preservation (Smitz et al., 2010). Follicle culture has successfully been performed in mice, larger mammals, and non-human primates (Eppig and O’Brien, 1996; reviewed in Simon et al., 2020). However, translation of follicle culture to humans has been difficult due to limited access of human ovarian tissue for research purposes. Moreover, it takes several months for human preantral follicles to reach their terminal diameters of 20 mm in vivo which poses inherent challenges in vitro of supporting such large structures over extended time. To date, there have been limited but pioneering studies focused on the growth of human ovarian follicles ex vivo. In 2009, isolated human ovarian secondary follicles, encapsulated them in alginate hydrogels, and grew them in culture for 30days (Xu et al., 2009). These follicles grew, produced characteristic patterns of peptide and steroid hormones, and formed antral cavities; however, the in vitro grown oocytes were not meiotically competent (Xu et al., 2009). Six years later, Xiao and colleagues developed a two-step culture system in which human preantral follicles were encapsulated in alginate hydrogels until antrum formation, and then removed from the hydrogel and grown for up to 40days (Xiao et al., 2015). The new culture system was designed to mimic the changing physical environment of the growing follicle as it transitions from the rigid cortex to the permissive perimedullary region. Importantly, this system produced the first mature human metaphase II arrested (MII) eggs grown from isolated preantral stage follicles at an incidence of 20%(4 of 20 follicles)(Xiao et al., 2015). The next major advance occurred in 2018 when McLaughlin and colleagues used a multi-step culture system to grow human follicles all the way from the unilaminar (primordial and primary) stage to the antral stage (McLaughlin et al., 2018). This system involved in situ culture of human ovarian cortical fragments, isolation and growth of individual preantral follicles, isolation and culture of oocyte-granulosa cells complexes, and finally in vitro maturation. This integrated follicle culture system generated MII eggs at an incidence of 28%(9 of 32 follicles)(McLaughlin et al., 2018). However, gamete morphology was clearly compromised as the eggs had abnormally large first polar bodies, demonstrating the need of further culture refinements. In an article published in this issue of Human Reproduction, Xu et al.(2021) report a multi-step matrix-free follicle culture system with stage-specific anti-Mullerian Hormone (AMH) modulation that results in the production of what appear to be more morphologically normal human MII eggs from unilaminar follicles. This milestone represents a significant achievement in the development of more optimized culture systems for human preantral follicles. Over the past decade, this group has developed and fine-tuned this approach in a non-human primate model (Xu et al., 2011, 2013, 2016, 2018). The system involved growth of primordial and intermediary stage follicles to the primary or secondary stage in ovarian cortex during 3weeks of culture …
