title: Estrogen related receptor is required for the testicular development and for the normal sperm axoneme/mitochondrial derivatives in Drosophila males.
abstract: 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.
authors.affiliation: 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.
authors.forename: Snigdha
authors.initials: S
authors.lastname: Misra
authors.affiliation: Embryotoxicology Laboratory, Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), MG Marg, Lucknow, Uttar Pradesh, 226001, India.
authors.forename: Anuj Kumar
authors.initials: AK
authors.lastname: Pandey
authors.affiliation: 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.
authors.forename: Snigdha
authors.initials: S
authors.lastname: Gupta
authors.affiliation: 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.
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Embryotoxicology Laboratory, Environmental Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), MG Marg, Lucknow, Uttar Pradesh, 226001, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Khanna
authors.affiliation: Electron Microscopy Facility, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), MG Marg, Lucknow, Uttar Pradesh, 226001, India.
authors.forename: Jai
authors.initials: J
authors.lastname: Shankar
authors.affiliation: 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.
authors.forename: Kristipati
authors.initials: K
authors.lastname: Ravi Ram
mesh_terms: D000818:Animals; D054468:Axoneme / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D005298:Fertility; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000378:metabolism; D012669:Seminal Vesicles / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000002:abnormalities / Q000254:growth & development* / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C475538:ERR protein, Drosophila; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D055758:SOX9 Transcription Factor; C477648:Sox100B protein, Drosophila