Follicular cells acquire sertoli cell characteristics after oocyte loss
Follicular cells acquire sertoli cell characteristics after oocyte loss
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DOI：
10.1210/en.2005-0045
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发表时间：
2005-07-01
期刊：
影响因子：
4.8
通讯作者：
Magre, S
中科院分区：
文献类型：
--
作者：
Guigon, CJ;Coudouel, N;Magre, S
尽管有人提出在哺乳动物中雌性生殖细胞的缺失可能会诱导卵巢区室的雄性化，但至今尚无确凿的证据。为了直接解决这个问题，本研究旨在确定卵母细胞缺失后卵泡细胞的命运。我们利用γ射线照射选择性地去除雌性大鼠非生长卵泡中的卵母细胞，结果表明卵母细胞缺失的卵泡中的卵泡细胞能够存活、增殖，并随后获得支持细胞的形态特征：细胞质伸长、细胞核位于基底部以及特定的支持细胞连接——胞质特化结构。然而，这些类支持细胞表达雌性特异性标志物FOXL2（叉头框L2），而不表达雄性特异性标志物SOX - 9（Sry型高迁移率族盒转录因子 - 9），这表明颗粒细胞的分子特征得以维持。在转分化为类支持细胞之前，卵母细胞缺失的卵泡的卵泡细胞开始表达抗苗勒管激素和抑制素α亚单位，这些物质通常在卵泡生长开始时由颗粒细胞合成。对受照射雌性动物内分泌平衡的实验性调整表明，血浆促卵泡激素水平与类支持细胞的出现密切相关。除了为卵母细胞在维持颗粒细胞表型中的关键作用提供实验证据外，这些结果还强调颗粒细胞向支持细胞的转分化是以多步骤的方式发生的，需要颗粒细胞成熟且依赖于内分泌环境。
Although it has been suggested that in mammals the loss of female germ cells may induce the masculinization of the ovarian compartment, there has been as yet no conclusive demonstration. To directly address that question, the present study has been designed to determine the fate of follicular cells after oocyte loss. Using gamma-irradiation to selectively deplete oocytes in nongrowing follicles in female rats, we show that follicular cells in oocyte-depleted follicles survive, proliferate, and subsequently acquire morphological characteristics of Sertoli cells: elongated cytoplasm, basal location of the nucleus, and specific Sertoli cell junctions, the ectoplasmic specializations. These Sertoli-like cells express, however, the female-specific marker FOXL2 ( Forkhead L2) but not the male sex-specific marker SOX-9 (Sry-type high-mobility-group box transcription factor-9) underlying the maintenance of molecular characteristics of granulosa cells. Before transdifferentiating into Sertoli-like cells, follicular cells of oocyte-depleted follicles initiate the expression of anti-Mullerian hormone and inhibin alpha-subunit that are typically synthesized by granulosa cells from the onset of follicular growth. Experimental modifications of the endocrine balance of the irradiated females show that there is a close relationship between plasma FSH levels and the occurrence of Sertoli-like cells. In addition to providing experimental evidence for the crucial role of the oocyte in granulosa cell phenotype maintenance, these results emphasize that the transdifferentiation of granulosa cells into Sertoli cells occurs in a multistep fashion, requiring the maturation of granulosa cells and depending on the endocrine milieu.