Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, Robinson Institute, University of Adelaide, SA, Australia.
PLoS One. 2013;8(2):e55578. doi: 10.1371/journal.pone.0055578. Epub 2013 Feb 7.
Ovarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells penetrate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 80) we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 26 markers for GREL and other cells and extracellular matrix we conducted immunohistochemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the gonadal ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are always separated from the stroma by a basal lamina. Around 130 days of gestation the stroma expands laterally below the outermost layers of GREL cells forming a sub-epithelial basal lamina and establishing an epithelial-stromal interface. It is at this stage that a mature surface epithelium develops from the GREL cells on the surface of the ovary primordium. Expansion of the stroma continues to partition the ovigerous cords into smaller groups of cells eventually forming follicles containing an oogonium/oocyte surrounded by GREL cells, which become granulosa cells, all enclosed by a basal lamina. Thus in contrast to the prevailing theory, the ovarian surface epithelial cells do not penetrate into the ovary to form the granulosa cells of follicles, instead ovarian surface epithelial cells and granulosa cells have a common precursor, the GREL cell.
卵巢滤泡颗粒细胞围绕并滋养卵母细胞,并产生性激素。人们认为,在发育过程中,卵巢表面上皮细胞穿透卵巢,并与卵原细胞结合形成卵泡时发育为颗粒细胞。我们使用牛胎儿卵巢(n = 80)鉴定了一种新型细胞类型,称为 Gonadal Ridge Epithelial-Like 的 GREL。使用 26 种 GREL 和其他细胞及细胞外基质的标志物,我们进行了免疫组织化学和电子显微镜检查,并按时间顺序追踪了发育过程中的所有体细胞类型。在妊娠 70 天之前,生殖嵴/卵巢原基由中肾表面上皮细胞的 GREL 细胞增殖形成。原始生殖细胞(PGC)迁移到卵巢原基中。妊娠 70 天后,来自下方中肾的基质开始穿透原基,将发育中的卵巢分隔成由 GREL 细胞和 PGC/卵原细胞组成的不规则形状的卵原细胞索。重要的是,我们发现这些索总是与基质由基膜隔开。妊娠 130 天左右,基质在 GREL 细胞的最外层下方横向扩展,形成上皮下基膜,并建立上皮-基质界面。正是在这个阶段,从卵巢原基表面的 GREL 细胞发育出成熟的表面上皮。基质的扩展继续将卵原细胞索分隔成更小的细胞群,最终形成包含卵原细胞/卵母细胞的卵泡,卵母细胞周围有 GREL 细胞,它们被基膜包围。因此,与流行的理论相反,卵巢表面上皮细胞不会穿透卵巢形成卵泡的颗粒细胞,相反,卵巢表面上皮细胞和颗粒细胞具有共同的前体细胞,即 GREL 细胞。