Elucidating Gene Regulatory Mechanisms for Sperm Function Through the Integration of Classical and Systems Approaches in C. elegans

Abstract

From worms to mammals, successful spermatogenesis depends on a gene expression profile that balances activating and repressive mechanisms. Besides developmental control of specific spermatogenic genes, male fertility requires temporal shifts in global gene expression and dramatic changes in chromatin structure and condensation. Recent studies are beginning to elucidate the molecular processes that both drive these temporal changes in gene expression and underlie fertility. In this review, we provide an overview of relevant C. elegans studies that have laid the groundwork for modern approaches. Next, we highlight recent studies that investigate how gene expression in C. elegans is modulated during spermatogenesis. These studies use large-scale genomic profiling in combination with bioinformatics, genetics, biochemistry, and in vitro methods to target specific stages or processes during sperm formation. Such studies are beginning to elucidate the multiple layers of gene regulation required during spermatogenesis, i.e., transcriptional, post-transcriptional, and epigenetic. Moreover, knowledge of how C. elegans coordinately regulates gene expression during spermatogenesis promises to provide key insights into parallel processes in mammals that are vital for fertility.

Gonad morphogenesis defects drive hybrid male sterility in asymmetric hybrid breakdown of Caenorhabditis nematodes

“…latens . Recent evidence suggests spermatogenesis genes in C. elegans are regulated by small RNA based mechanisms, several of which are transmitted maternally and are critical for maintenance of male fertility (Batista et al ; Wang and Reinke ; Conine et al ; Wu et al ; Johnson and Spence ). Drosophila also shows misregulation of small RNAs in hybrids (Kelleher et al ).…”

“…Any or all of the above explanations could contribute to the reciprocal cross asymmetry in hybrid sterility and inviability in hybrids of C. remanei and C. latens. Recent evidence suggests spermatogenesis genes in C. elegans are regulated by small RNA based mechanisms, several of which are transmitted maternally and are critical for maintenance of male fertility (Batista et al 2008;Wang and Reinke 2008;Conine et al 2009;Wu et al 2010;Johnson and Spence 2011). Drosophila also shows misregulation of small RNAs in hybrids (Kelleher et al 2012).…”

The Genetics and Cell Biology of Fertilization

“…Although some investigators are beginning to include both residual body formation and initial events of spermatid maturation as part of “spermiogenesis” (Wu, Nera et al 2010), within the C. elegans literature, spermiogenesis is most frequently defined as the subsequent dramatic morphogenesis of spherical, sessile spermatids into amoeboid, motile, fertilization-competent spermatozoa (Shakes and Ward 1989). Cellular changes include plasma membrane flow to the site of the newly developing pseudopod, fusion of caveolae-like membranous organelles (MO) to the cell body plasma membrane, and the formation of a dynamic MSP pseudopod cytoskeleton.…”