Genetic variants related to gap junctions and hormone secretion influence conception rates in cows

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Abstract

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 junctionrelated 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 folliclestimulating 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.

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Sugimoto, M., Sasaki, S., Gotoh, Y., Nakamura, Y., Aoyagi, Y., Kawahara, T., & Sugimoto, Y. (2013). Genetic variants related to gap junctions and hormone secretion influence conception rates in cows. Proceedings of the National Academy of Sciences of the United States of America, 110(48), 19495–19500. https://doi.org/10.1073/pnas.1309307110

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