BMP4 Cooperates with Retinoic Acid to Induce the Expression of Differentiation Markers in Cultured Mouse Spermatogonia.
BMP4 Cooperates with Retinoic Acid to Induce the Expression of Differentiation Markers in Cultured Mouse Spermatogonia.
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BMP4 与视黄酸配合诱导培养的小鼠精原细胞中分化标志物的表达。
DOI：
10.1155/2016/9536192
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发表时间：
2016
影响因子：
4.3
通讯作者：
Han C
中科院分区：
文献类型：
--
作者：
Yang Y;Feng Y;Feng X;Liao S;Wang X;Gan H;Wang L;Lin X;Han C
精子发生是由精原干细胞（SSCs）的增殖和分化维持的。然而，控制这些过程的分子在很大程度上仍然未知。本研究建立了一种简化的高浓度含血清培养体系，用于培养小鼠精原干细胞。精原干细胞标记和移植结果分析表明，培养的精原细胞在体外长期增殖后仍保持干细胞特性。利用该培养体系，探讨骨形态发生蛋白4（BMP 4）的表达及功能。免疫组化显示BMP 4主要在生殖细胞中表达，其水平随着精子发生的进展而增加。BMP 4受体BMPR 1A和BMPRII存在于精原细胞、精母细胞和圆形精子细胞中。此外，尽管这两个基因的mRNA存在于小鼠Sertoli细胞，只有BMPRII被检测到通过使用蛋白质印迹分析。外源性BMP 4本身不能诱导精原细胞分化标志基因Stra 8和c-Kit的表达，而BMP 4与维甲酸（RA）有明显的协同作用。用BMP 4拮抗剂Noggin预处理培养的精原细胞可以抑制RA诱导的这两个标记基因的表达。结论：BMP-4可能通过自分泌作用与RA协同诱导精原细胞分化。
Spermatogenesis is sustained by the proliferation and differentiation of spermatogonial stem cells (SSCs). However, the molecules controlling these processes remain largely unknown. Here, we developed a simplified high concentration serum-containing system for the culture of mouse SSCs. Analysis of SSCs markers and transplantation results revealed that the cultured spermatogonia retained stem cell characteristics after long-term in vitro propagation. Using this culture system, the expression and function of bone morphogenetic protein 4 (BMP4) were explored. Immunostaining showed that BMP4 was predominantly expressed in germ cells and that its level increased as spermatogenesis progresses. BMP4 receptors BMPR1A and BMPRII were present in spermatogonia, spermatocytes, and round spermatids. Moreover, despite the mRNAs of these two genes being present in mouse Sertoli cells, only BMPRII was detected by using Western blotting assays. While exogenous BMP4 by itself did not induce the expression of Stra8 and c-Kit, two marker genes of differentiating spermatogonia, a significant cooperative effect of BMP4 and retinoic acid (RA) was observed. Moreover, pretreatment of cultured spermatogonia with the BMP4 antagonist Noggin could inhibit RA-induced expression of these two marker genes. In conclusion, BMP4 may exert autocrine effects and act cooperatively with RA to induce the differentiation of spermatogonia in vivo.
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影响因子：
5.2
作者：
He, Zuping;Jiang, Jiji;Kokkinaki, Maria;Dym, Martin
通讯作者：
Dym, Martin
DOI：
10.1073/pnas.241508898
发表时间：
2001-11-20
影响因子：
11.1
作者：
Fujiwara, T;Dunn, NR;Hogan, BLM
通讯作者：
Hogan, BLM
影响因子：
56.9
作者：
Bowles, J;Knight, D;Koopman, P
通讯作者：
Koopman, P
影响因子：
2.5
作者：
Itman, Catherine;Loveland, Kate Lakoski
通讯作者：
Loveland, Kate Lakoski
DOI：
10.1073/pnas.0807297105
发表时间：
2008-09-30
影响因子：
11.1
作者：
Anderson, Ericka L.;Baltus, Andrew E.;Page, David C.
通讯作者：
Page, David C.