Estrogen Receptor β2 Oversees Germ Cell Maintenance and Gonadal Sex Differentiation in Medaka, Oryzias latipes
Estrogen Receptor β2 Oversees Germ Cell Maintenance and Gonadal Sex Differentiation in Medaka, Oryzias latipes
复制标题
DOI：
10.1016/j.stemcr.2019.07.013
复制
发表时间：
2019-08-13
影响因子：
5.9
通讯作者：
Nagahama, Yoshitaka
中科院分区：
文献类型：
--
作者：
Chakraborty, Tapas;Mohapatra, Sipra;Nagahama, Yoshitaka
在脊椎动物中，雌激素受体对于雌激素相关的早期性腺发育是必需的。我们以前的研究揭示了雌激素受体β 2（ER β 2）在青鳉胚胎发生过程中的性二态表达，在这里，我们研究了雌激素受体β 2在雌性性腺发育和维护中的功能重要性，使用跨代ER β 2敲低（ER β 2-KD）系和ER β 2无效突变体。我们发现ER β 2减少有利于男性偏好的基因转录，抑制女性反应基因表达，并影响SDF 1a和CXCR 4 b共同辅助的趋化性原始生殖细胞（PGC）迁移。SDF 1a和CXXR 4 b的共过表达恢复了ER β 2-KD/KO相关的PGC误迁移。进一步的分析证实，ER β 2的减少增加了细胞内Ca 2+浓度，破坏了细胞内和细胞外钙稳态，并引发了自噬生殖细胞降解和生殖细胞损失，在某些情况下，最终影响了XX女性的性发育。本研究有望提高我们对生殖细胞维持和性谱的理解，从而为生殖疾病的管理开辟新的途径。
In vertebrates, estrogen receptors are essential for estrogen-associated early gonadal sex development. Our previous studies revealed sexual dimorphic expression of estrogen receptor beta 2 (ER beta 2) during embryogenesis of medaka, and here we investigated the functional importance of ER beta 2 in female gonad development and maintenance using a transgenerational ER beta 2-knockdown (ER beta 2-KD) line and ER beta 2-null mutants. We found that ER beta 2 reduction favored male-biased gene transcription, suppressed female-responsive gene expression, and affected SDF1a and CXCR4b co-assisted chemotactic primordial germ cell (PGC) migration. Co-overexpression of SDF1a and CXXR4b restored the ER beta 2-KD/KO associated PGC mismigration. Further analysis confirmed that curtailment of ER beta 2 increased intracellular Ca2+ concentration, disrupted intra- and extracellular calcium homeostasis, and instigated autophagic germ cell degradation and germ cell loss, which in some cases ultimately affected the XX female sexual development. This study is expected improve our understanding of germ cell maintenance and sex spectrum, and hence open new avenues for reproductive disorder management.