McElhinney Kathryn L, Rowell Erin E, Laronda Monica M
Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Bioengineering (Basel). 2024 Jul 19;11(7):734. doi: 10.3390/bioengineering11070734.
The only fertility preservation and subsequent restoration option for many patients facing gonadotoxic treatments is ovarian tissue cryopreservation and transplantation. While this process is successful for some, there is significant room for improvement to extend the life of the transplant and to make it safe for patients that may have metastatic disease within their ovarian tissue. We need a deeper understanding of how the physical properties of the ovarian microenvironment may affect folliculogenesis to engineer an environment that supports isolated follicles and maintains primordial follicle quiescence. Bovine ovaries were used here as a monovulatory model of folliculogenesis to examine the effects of primordial follicle activation and growth under different physical conditions. We found that there were no differences in activation, growth or survival when primordial follicles were cultured in isolation or in situ (remaining in the tissue) under two significantly differently rigid alginate gels. To determine if the extra rigid environment did not affect activation in isolated follicles due to an immediate activation event, we used 5-ethynyl-2'-deoxyuridine (EdU) to track follicle activation during the isolation process. We identified EdU incorporation in granulosa cells after primordial follicles were isolated from the surrounding extracellular matrix (ECM). These findings support that isolation of primordial follicles from the ECM is an activating event and that the differentially rigid environments assessed here had no effect on follicle growth. Further work is needed to suppress activation in primordial follicles to maintain the ovarian reserve and extend the life of an ovarian tissue transplant.
对于许多面临性腺毒性治疗的患者来说，唯一的生育力保存及后续恢复选择是卵巢组织冷冻保存和移植。虽然这一过程对一些患者是成功的，但在延长移植组织寿命以及确保卵巢组织中可能存在转移性疾病的患者安全方面仍有很大的改进空间。我们需要更深入地了解卵巢微环境的物理特性如何影响卵泡发生，从而构建一个支持孤立卵泡并维持原始卵泡静止状态的环境。在此，我们使用牛卵巢作为卵泡发生的单排卵模型，以研究不同物理条件下原始卵泡激活和生长的影响。我们发现，在两种硬度差异显著的藻酸盐凝胶中，将原始卵泡单独培养或原位培养（留在组织中）时，其激活、生长或存活情况没有差异。为了确定由于立即激活事件，额外的刚性环境是否不会影响孤立卵泡的激活，我们使用5-乙炔基-2'-脱氧尿苷（EdU）来追踪分离过程中的卵泡激活情况。我们在原始卵泡从周围细胞外基质（ECM）分离后，在颗粒细胞中鉴定到了EdU掺入。这些发现支持从ECM中分离原始卵泡是一个激活事件，并且这里评估的不同刚性环境对卵泡生长没有影响。需要进一步开展工作来抑制原始卵泡的激活，以维持卵巢储备并延长卵巢组织移植的寿命。
