Loss of the nuclear receptor corepressor SLIRP compromises male fertility

Shane M Colley, Larissa Wintle, Richelle Searles, Victoria Russell, Renee C Firman, Stephanie Jay Smith, Kathleen Debra DeBoer, Donna Jo Merriner, Ben Genevieve, Jacqueline M Bentel, Bronwyn Stuckey, Michael R Phillips, Leigh Simmons, David Morritz de Kretser, Moira Kathleen O'Bryan, Peter Leedman

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13 Citations (Scopus)

Abstract

Nuclear receptors (NRs) and their coregulators play fundamental roles in initiating and directing gene expression influencing mammalian reproduction, development and metabolism. SRA stem Loop Interacting RNA-binding Protein (SLIRP) is a Steroid receptor RNA Activator (SRA) RNA-binding protein that is a potent repressor of NR activity. SLIRP is present in complexes associated with NR target genes in the nucleus; however, it is also abundant in mitochondria where it affects mitochondrial mRNA transcription and energy turnover. In further characterisation studies, we observed SLIRP protein in the testis where its localization pattern changes from mitochondrial in diploid cells to peri-acrosomal and the tail in mature sperm. To investigate the in vivo effects of SLIRP, we generated a SLIRP knockout (KO) mouse. This animal is viable, but sub-fertile. Specifically, when homozygous KO males are crossed with wild type (WT) females the resultant average litter size is reduced by approximately one third compared with those produced by WT males and females. Further, SLIRP KO mice produced significantly fewer progressively motile sperm than WT animals. Electron microscopy identified disruption of the mid-piece/annulus junction in homozygous KO sperm and altered mitochondrial morphology. In sum, our data implicates SLIRP in regulating male fertility, wherein its loss results in asthenozoospermia associated with compromised sperm structure and mitochondrial morphology.
Original languageEnglish
Pages (from-to)1 - 8
Number of pages8
JournalPLoS ONE
Volume8
Issue number8 (Art. ID: e70700)
DOIs
Publication statusPublished - 2013

Cite this

Colley, S. M., Wintle, L., Searles, R., Russell, V., Firman, R. C., Smith, S. J., DeBoer, K. D., Merriner, D. J., Genevieve, B., Bentel, J. M., Stuckey, B., Phillips, M. R., Simmons, L., de Kretser, D. M., O'Bryan, M. K., & Leedman, P. (2013). Loss of the nuclear receptor corepressor SLIRP compromises male fertility. PLoS ONE, 8(8 (Art. ID: e70700)), 1 - 8. https://doi.org/10.1371/journal.pone.0070700