Embryotoxicology Laboratory, Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), MG Marg, Lucknow, Uttar Pradesh, 226001, India.
Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR campus, Lucknow, Uttar Pradesh, 226001, India.
Sci Rep. 2017 Jan 17;7:40372. doi: 10.1038/srep40372.
Estrogen related receptors (ERRs), categorized as orphan nuclear receptors, are critical for energy homeostasis and somatic development. However, significance of ERRs in the development of reproductive organs/organelles/cells remain poorly understood, albeit their homology to estrogen receptors. In this context, here, we show that knockdown of ERR in the testes leads to improperly developed testes with mis-regulation of genes (aly, mia, bruce, bam, bgcn, fzo and eya) involved in spermatogenesis, resulting in reduced male fertility. The observed testicular deformity is consistent with the down-regulation of SOX-E group of gene (SOX100B) in Drosophila. We also show dispersion/disintegration of fusomes (microtubule based structures associated with endoplasmic reticulum derived vesicle, interconnecting spermatocytes) in ERR knockdown testes. A few ERR knockdown testes go through spermatogenesis but have significantly fewer sperm. Moreover, flagella of these sperm are defective with abnormal axoneme and severely reduced mitochondrial derivatives, suggesting a possible role for ERR in mitochondrial biogenesis, analogous to mammalian ERRα. Interestingly, similar knockdown of remaining seventeen nuclear receptors did not yield a detectable reproductive or developmental defect in Drosophila. These findings add newer dimensions to the functions envisaged for ERR and provide the foundation for deciphering the relevance of orphan nuclear receptors in ciliopathies and testicular dysgenesis.
雌激素相关受体（ERRs），归类为孤儿核受体，对于能量平衡和体细胞发育至关重要。然而，尽管它们与雌激素受体具有同源性，但 ERRs 在生殖器官/细胞器/细胞发育中的意义仍知之甚少。在这种情况下，我们在这里表明，睾丸中 ERR 的敲低导致睾丸发育异常，参与精子发生的基因（aly、mia、bruce、bam、bgcn、fzo 和 eya）失调，导致雄性生育能力降低。观察到的睾丸畸形与果蝇中 SOX-E 基因（SOX100B）的下调一致。我们还显示 ERR 敲低睾丸中的融合体（与内质网衍生小泡相关的微管为基础的结构，连接精母细胞）的分散/解体。少数 ERR 敲低睾丸经历精子发生，但精子数量明显减少。此外，这些精子的鞭毛有缺陷，轴突异常，线粒体衍生物严重减少，表明 ERR 在类似于哺乳动物 ERRα 的线粒体生物发生中可能发挥作用。有趣的是，在果蝇中，类似地敲低其余十七个核受体并没有导致可检测到的生殖或发育缺陷。这些发现为 ERR 的功能增添了新的维度，并为阐明孤儿核受体在纤毛病和睾丸发育不良中的相关性提供了基础。
