Implication of SLIT3-ROBO1/ROBO2 in granulosa cell proliferation, differentiation and follicle selection in the prehierarchical follicles of hen ovary
Implication of SLIT3-ROBO1/ROBO2 in granulosa cell proliferation, differentiation and follicle selection in the prehierarchical follicles of hen ovary
复制标题
SLIT3-ROBO1/ROBO2在母鸡卵巢分级前卵泡颗粒细胞增殖、分化和卵泡选择中的意义
DOI：
10.1002/cbin.11063
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发表时间：
2018
影响因子：
3.9
通讯作者：
Jinghua Zhao
中科院分区：
文献类型：
--
作者：
Rifu Xu;Ning Qin;Xiaoxing Xu;Xue Sun;Xiaoxia Chen;Jinghua Zhao
SLIT/ROBO信号通路通过卵泡内自分泌和/或旁分泌方式参与鸡卵巢前级卵泡的发育。SLIT 3是SLIT/ROBO家族的关键组分之一，作为一种配体，可能与四种受体ROBO 1、ROBO 2、ROBO 3和ROBO 4相互作用。但SLIT 3在鸡卵泡发育中的确切作用及其调控机制尚不清楚。本研究旨在探讨SLIT 3在鸡卵巢颗粒细胞（granulosa cell，GC）增殖、分化和卵泡选择中的作用及其分子调控。我们发现SLIT 3与四种ROBO受体发生物理相互作用，但ROBO 1和ROBO 2基因的表达比ROBO 3和ROBO 4基因的表达更容易受到SLIT 3配体的调控。此外，siRNA介导的滤泡GC中SLIT 3的敲低导致细胞增殖的显著增加。相反，SLIT 3的过度表达导致GC增殖显著减少。此外，过表达的SLIT 3显著降低了GC中促卵泡激素（FSHR）、生长和分化因子9（GDF 9）、类固醇生成急性调节蛋白（星星）和细胞色素P450 11 A1（CYP 11 A1）的mRNA和蛋白表达水平。这些结果表明，SLIT 3可能对GC增殖、分化和卵泡选择起抑制作用，并且SLIT 3在GC增殖中的这些抑制作用可以通过siRNA介导的ROBO 1和ROBO 2受体的敲低来抑制。本研究为进一步研究SLIT 3 ‐ ROBO 1/2信号通路调控鸡卵巢前级卵泡发育的分子机制奠定了基础。
The SLIT/ROBO pathway has been implicated in prehierarchical follicular development of hen ovary by an intrafollicular autocrine and/or paracrine fashion. SLIT3, one of the key components of the SLIT/ROBO family, serves as a ligand that potentially interacts with the four receptors, ROBO1, ROBO2, ROBO3 and ROBO4. But the exact roles and regulatory mechanism of SLIT3 in chicken ovarian follicle development remain largely unclear. The present study was conducted to investigate the potential roles and molecular regulation ofSLIT3in granulosa cell (GC) proliferation, differentiation and follicle selection within the prehierarchical follicles of hen ovary. We found that SLIT3 interacts physically with the four ROBO receptors, but the expression of the ROBO1 and ROBO2 genes are more susceptible to the regulation of SLIT3 ligand than that of the ROBO3 and ROBO4 genes. Moreover, the siRNA‐mediated knockdown ofSLIT3in the follicular GCs leads to a significant increase in cell proliferation. Conversely, overexpression ofSLIT3results in a remarkable reduction in GC proliferation. Furthermore, the overexpressed SLIT3 has notably decreased the mRNA and protein expression levels of follicle‐stimulating hormone (FSHR), growth and differentiation factor 9 (GDF9), steroidogenic acute regulatory protein (STAR) and cytochrome P450 11A1 (CYP11A1) in the GCs. These results indicated that SLIT3 may play an inhibitory effect on GC proliferation, differentiation and follicle selection, and these suppressive actions of SLIT3 in the GC proliferation can be prohibited by the siRNA‐mediated knockdown of ROBO1 and ROBO2 receptors. The current data provide a basis for further investigation of molecular mechanisms of SLIT3‐ROBO1/2 pathway in controlling the prehierarchical follicle development of the hen ovary.