Function and mechanism of germline small non-coding RNAs in sperm and embryos
Using mice as a model to investigate functions and mechanisms of small ncRNAs in spermatogenesis and embryogenesis
Male infertility is a disorder of complex origins encompassing a broad spectrum of clinical symptoms. Despite the established reference parameters for semen quality by the World Health Organization and advancement in diagnostic tests, the underlying causes of ~40% of all male infertility cases could not be identified. The implication goes beyond the affected individuals. In assisted reproductive technology, the reproductive health of the father plays an important role in embryo viability, calling for a deeper understanding of male reproduction and new diagnostic tools.
A broader biological role for sperm epigenetic molecules in multiple species. tRNA-derived small RNAs and microRNAs (miRNAs) have been proposed to mediate paternal contribution to the offspring
The need to better understand male reproduction grows also in light of transgenerational influences of sperm epigenetic molecules, which regulate the expression of genes without modifying their DNA sequences. Small non-coding RNAs (ncRNAs)—18–40nt RNAs that do not encode proteins—are such epigenetic molecules that have been proposed to transmit the consequences of paternal diet, metabolic status, chronic stress to the offspring.
Studying the function of pachytene piRNAs using CRISPR/Cas9, mouse genetics, and sequencing
We are interested in the paternal contribution of a class of ~30nt small ncRNAs called pachytene PIWI-interacting RNAs (piRNAs) to early embryogenesis. Specific to mammals, pachytene piRNAs are extraordinarily abundant in the adult male germline. Unlike the better-known transposon-derived piRNAs, most pachytene piRNAs harbor unique sequences produced by defined loci in the genome. Since their discovery in 2006, our and others’ work has established a vital role for pachytene piRNAs in male fertility. These small ncRNAs are indispensable for the formation and fertilizing capability of mature sperm. Furthermore, by directly deleting pachytene piRNAs in mice, we uncovered a role for paternal pachytene piRNAs in preimplantation embryogenesis.
Our lab aims to understand the mechanism underlying the transgenerational role of paternal pachytene piRNAs using a wide range of techniques, including CRISPR/Cas9-mediated mutant mouse generation, embryo manipulation, and high-throughput sequencing.