Saunders Diane C, Laronda Monica M
Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA; Department of Pediatrics, Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA; Department of Pediatrics, Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Best Pract Res Clin Obstet Gynaecol. 2025 Jul 17;102:102641. doi: 10.1016/j.bpobgyn.2025.102641.
Many individuals with ovaries that utilize fertility preservation because of their progressive disease or gonadotoxic treatment must use ovarian tissue cryopreservation (OTC). Currently, the only option for fertility and hormone restoration after OTC is ovarian tissue transplantation (OTT), or autologous grafting of ovarian tissue. Individuals with disease in their ovaries do not have options to produce a biological child or restore their full ovarian hormone milieu. The goal of developing a bioprosthetic ovary would support full fertility and hormone restoration long-term as a safer and ideally more efficient option than current OTT techniques. In order to develop a bioprosthetic ovary, the field must understand how to control the rate of primordial follicle activation and support the follicle growth through development and maturation into a good quality egg. The follicular microenvironment changes across the lifespan and the growing oocyte is surrounded by a different microenvironment as it is localized in different compartments within the ovary over folliculogenesis. The human ovarian interstitial cells, scaffold proteins and the juxtracrine, paracrine and endocrine signals that influence folliculogenesis are just being realized with the increased data generated by mapping technologies. Recent research has utilized bioengineering tools to interrogate these follicular microenvironment components and better understand the components that are necessary and sufficient to sustain folliculogenesis and produce good quality eggs. However, there are several biological, scalability and regulatory hurdles to overcome in order to realize a bioprosthetic ovary, including the ability to isolate sufficient primordial follicles from their dense stroma while maintaining their quiescence and subsequent transplant longevity. This chapter reviews these components and encourages researchers to continue on these research quests to increase the foundational understanding of human folliculogenesis and develop near-future solutions for infertility on the way to developing the ideal bioprosthetic ovary.
许多因疾病进展或性腺毒性治疗而需要保留生育功能的卵巢功能正常个体，必须采用卵巢组织冷冻保存（OTC）。目前，OTC后恢复生育能力和激素水平的唯一选择是卵巢组织移植（OTT），即自体移植卵巢组织。卵巢患病的个体无法生育亲生子女或恢复完整的卵巢激素环境。开发生物人工卵巢的目标是长期支持完全的生育能力和激素恢复，作为一种比当前OTT技术更安全且理想情况下更有效的选择。为了开发生物人工卵巢，该领域必须了解如何控制原始卵泡激活的速率，并支持卵泡通过发育和成熟成长为优质卵子。卵泡微环境在整个生命周期中会发生变化，随着卵泡发生过程中生长中的卵母细胞位于卵巢内不同隔室，它被不同的微环境所包围。随着绘图技术产生的数据增加，人们才刚刚认识到影响卵泡发生的人类卵巢间质细胞、支架蛋白以及旁分泌、自分泌和内分泌信号。最近的研究利用生物工程工具来探究这些卵泡微环境成分，并更好地了解维持卵泡发生和产生优质卵子所必需和充分的成分。然而，为了实现生物人工卵巢，还需要克服几个生物学、可扩展性和监管方面的障碍，包括从致密基质中分离出足够数量的原始卵泡同时保持其静止状态以及随后移植后的长期存活能力。本章将对这些成分进行综述，并鼓励研究人员继续这些研究探索，以增进对人类卵泡发生的基础理解，并在开发理想的生物人工卵巢的道路上为不孕症开发近期解决方案。
