Christensen Alice P, Patel Saloni H, Grasa Patricia, Christian Helen C, Williams Suzannah A
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women׳s Centre, Level 3, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Dev Biol. 2015 May 15;401(2):287-98. doi: 10.1016/j.ydbio.2014.12.024. Epub 2014 Dec 31.
Maintaining follicle integrity during development, whereby each follicle is a functional unit containing a single oocyte, is essential for the generation of healthy oocytes. However, the mechanisms that regulate this critical function have not been determined. In this paper we investigate the role of the oocyte in maintaining follicle development. To investigate this role, we use a mouse model with oocyte-specific deletion of C1galt1 which is required for the generation of core 1-derived O-glycans. The loss of oocyte-generated O-glycans results in the joining of follicles and the generation of Multiple-Oocyte Follicles (MOFs). The aim was to determine how Mutant follicle development is modified thus enabling follicles to join. Extracellular matrix and follicle permeability were studied using histology, immunohistochemistry and electron microscopy (EM). In ovaries containing Mutant Oocytes, the Follicle basal lamina (FBL) is altered both functionally and structurally from the primary stage onwards with Mutant follicles possessing unexpectedly thicker FBL. In Mutant ovaries, the theca cell layer is also modified with intermingling of theca between adjacent follicles. MOF function was analysed but despite increased numbers of preantral MOFs in Mutants, these do not reach the preovulatory stage after gonadotrophin stimulation. We propose a model describing how oocyte initiated changes in FBL and theca cells result in follicles joining. These data reveal new and important roles for the oocyte in follicle development and follicle integrity.
在卵泡发育过程中维持卵泡完整性至关重要，每个卵泡都是一个包含单个卵母细胞的功能单位，这对于产生健康的卵母细胞是必不可少的。然而，调节这一关键功能的机制尚未确定。在本文中，我们研究了卵母细胞在维持卵泡发育中的作用。为了研究这一作用，我们使用了一种小鼠模型，该模型中卵母细胞特异性缺失C1galt1，而C1galt1是生成核心1衍生的O-聚糖所必需的。卵母细胞生成的O-聚糖的缺失导致卵泡融合并产生多卵母细胞卵泡（MOF）。目的是确定突变卵泡的发育如何被改变从而使卵泡能够融合。使用组织学、免疫组织化学和电子显微镜（EM）研究细胞外基质和卵泡通透性。在含有突变卵母细胞的卵巢中，从初级阶段开始，卵泡基底层（FBL）在功能和结构上都发生了改变，突变卵泡的FBL意外地更厚。在突变卵巢中，卵泡膜细胞层也发生了改变，相邻卵泡之间的卵泡膜相互交织。对MOF功能进行了分析，但尽管突变体中窦前MOF数量增加，但在促性腺激素刺激后它们并未达到排卵前阶段。我们提出了一个模型，描述卵母细胞如何引发FBL和卵泡膜细胞的变化从而导致卵泡融合。这些数据揭示了卵母细胞在卵泡发育和卵泡完整性中的新的重要作用。
