Molecular Effects of Polymorphism in the 3'UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins.

• Main Authors: Mayumi Sugimoto, Yusaku Gotoh, Takayoshi Kawahara, Yoshikazu Sugimoto
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2015-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC4493121?pdf=render

Conception rates among dairy cows in Japan have declined in recent decades. To enhance our understanding of the genes involved in conception rates, we conducted a genome-wide association study (GWAS) using 822 Holsteins and identified a single-nucleotide polymorphism (SNP) associated with conception rate: A+169G in the 3' untranslated region (UTR) of unc-5 homolog C (UNC5C). Cows with higher conception rates carried the A polymorphism in the UNC5C 3'UTR. Luciferase assays and quantitative analysis of allele ratios revealed that UNC5C transcripts with the A polymorphism were expressed at higher levels than those carrying the G polymorphism. UNC5C transmits either pro- or anti-apoptotic signals depending on the availability of its ligand, Netrin-1. UNC5C expression is negatively regulated by reproductive homeobox X-linked 5 (Rhox5), and the Rhox5 locus is methylated by G9a methyltransferase. G9a-knockout mice have previously been demonstrated to be subfertile, and we found that UNC5C, G9a, and Netrin-1 expression levels increased from the 4-cell stage to the blastocyst stage in fertilized murine embryos, whereas Rhox5 expression decreased. Repression of UNC5C, G9a, or Netrin-1 or forced expression of Rhox5 in the anterior nucleus stage inhibited development to the blastocyst stage, suggesting that cows carrying the G polymorphism in UNC5C might have lower conception rates because of the poor development of preimplantation embryos. This study provides novel insights into the role of UNC5C during embryonic development.