Activation of the Hedgehog pathway in the mouse fetal ovary leads to ectopic appearance of fetal Leydig cells and female pseudohermaphroditism.
Activation of the Hedgehog pathway in the mouse fetal ovary leads to ectopic appearance of fetal Leydig cells and female pseudohermaphroditism.
复制标题
DOI：
10.1016/j.ydbio.2009.02.025
复制
发表时间：
2009-05-01
影响因子：
2.7
通讯作者：
Yao, Humphrey H. -C.
中科院分区：
文献类型：
--
作者：
Barsoum, Ivraym B.;Bingham, Nathan C.;Parker, Keith L.;Jorgensen, Joan S.;Yao, Humphrey H. -C.
哺乳动物性腺中正确的细胞命运决定对于性别认同的建立至关重要。Hedgehog（Hh）通路与包括性腺在内的各种器官的细胞命运决定有关。Desert Hedgehog（Dhh）基因是哺乳动物的三个Hh基因之一，与其他基因一起参与了小鼠胚胎Leydig细胞的形成。为了研究单独的Hh是否足以诱导胎儿Leydig细胞分化，我们异位激活了类固醇生成因子1（SF1）阳性的胎儿卵巢体细胞前体中的Hh通路。Hh活化可将SF 1阳性的卵巢体细胞转化为功能性的胎儿Leydig细胞。这些异位胎儿间质细胞产生雄激素和胰岛素样生长因子3（INLS 3），导致女性胚胎的男性化和卵巢下降。然而，雌性生殖系统保持完整，这是一个典型的雌性假两性畸形的例子。胎儿间质细胞的出现是Hh激活的直接结果，这一点在受影响的卵巢中缺乏其他睾丸成分是显而易见的。这项研究不仅提供了深入了解性腺细胞谱系特化的机制，也是一个模型，以了解性分化的缺陷。
Proper cell fate determination in mammalian gonads is critical for the establishment of sexual identity. The Hedgehog (Hh) pathway has been implicated in cell fate decision for various organs, including gonads. Desert Hedgehog (Dhh), one of the three mammalian Hh genes, has been implicated with other genes in the establishment of mouse fetal Leydig cells. To investigate whether Hh alone is sufficient to induce fetal Leydig cell differentiation, we ectopically activated the Hh pathway in Steroidogenic factor 1 (SF1)-positive somatic cell precursors of fetal ovaries. Hh activation transformed SF1-positive somatic ovarian cells into functional fetal Leydig cells. These ectopic fetal Leydig cells produced androgens and insulin-like growth factor 3 (INLS3) that cause virilization of female embryos and ovarian descent. However, the female reproductive system remained intact, indicating a typical example of female pseudohermaphroditism. The appearance of fetal Leydig cells was a direct consequence of Hh activation as evident by the absence of other testicular components in the affected ovary. This study provides not only insights into mechanisms of cell lineage specification in gonads, but also a model to understand defects in sexual differentiation.
登录
查看更多内容
影响因子：
6.6
作者：
Kubota, Y;Nef, S;Hutson, JM
通讯作者：
Hutson, JM
影响因子：
8.2
作者：
Magoffin, Denis A
通讯作者：
Magoffin, Denis A
影响因子：
2.7
作者：
Karl, J;Capel, B
通讯作者：
Capel, B
影响因子：
9.2
作者：
Bitgood, MJ;Shen, LY;McMahon, AP
通讯作者：
McMahon, AP
影响因子：
64.8
作者：
HENRIQUE, D;ADAM, J;ISHHOROWICZ, D
通讯作者：
ISHHOROWICZ, D