Genetic variants related to gap junctions and hormone secretion influence conception rates in cows.
The recent decline in fertility is a serious problem in the dairy industry. To overcome this problem, we performed a genome-wide association study using 384 Holsteins and identified four loci associated with conception rates. Two of them contained gap junction-related genes: PKP2 and CTTNBP2NL. Further analysis confirmed that PKP2 increased connexin 43, a gap junction protein, whereas CTTNBP2NL dephosphorylated connexin 43. Knockdown of PKP2 or overexpression of CTTNBP2NL inhibited embryo implantation in mice. The other two loci contained neuroendocrine-related genes: SETD6 and CACNB2. Additional experiments indicated that SETD6 is involved in the transcriptional regulation of gonadotropin-releasing hormone, whereas CACNB2 controlled the secretion of follicle-stimulating hormone in cattle. The total allele substitution effect of these genes on conception rate was 3.5%. Our findings reveal important roles for gap junction communication and the neuroendocrine system in conception and suggest unique selection methods to improve reproductive performance in the livestock industry.
National Livestock Breeding Center, Odakura, Nishigo, Fukushima 961-8511, Japan.
Mayumi
M
Sugimoto
Shinji
S
Sasaki
Yusaku
Y
Gotoh
Yuuki
Y
Nakamura
Yoshito
Y
Aoyagi
Takayoshi
T
Kawahara
Yoshikazu
Y
Sugimoto
D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics; D002417:Cattle / Q000235:genetics*; D018031:Connexin 43 / Q000378:metabolism; D005260:Female; D005306:Fertilization / Q000235:genetics*; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D008156:Luciferases; D051379:Mice; D051191:Plakophilins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011496:Protein Methyltransferases / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
D020746:Calcium Channels, L-Type; D018031:Connexin 43; D051191:Plakophilins; D005640:Follicle Stimulating Hormone; D008156:Luciferases; D011496:Protein Methyltransferases