Neupane Mahesh, Geary Thomas W, Kiser Jennifer N, Burns Gregory W, Hansen Peter J, Spencer Thomas E, Neibergs Holly L
Department Animal Sciences, Washington State University, Pullman, Washington, United States of America.
USDA-ARS, Fort Keogh Livestock and Range Research Laboratory, Miles City, Montana, United States of America.
PLoS One. 2017 Dec 11;12(12):e0188997. doi: 10.1371/journal.pone.0188997. eCollection 2017.
Infertility and subfertility negatively impact the economics and reproductive performance of cattle. Of note, significant pregnancy loss occurs in cattle during the first month of pregnancy, yet little is known about the genetic loci influencing pregnancy success and loss in cattle. To identify quantitative trait loci (QTL) with large effects associated with early pregnancy loss, Angus crossbred heifers were classified based on day 28 pregnancy outcomes to serial embryo transfer. A genome wide association analysis (GWAA) was conducted comparing 30 high fertility heifers with 100% success in establishing pregnancy to 55 subfertile heifers with 25% or less success. A gene set enrichment analysis SNP (GSEA-SNP) was performed to identify gene sets and leading edge genes influencing pregnancy loss. The GWAA identified 22 QTL (p < 1 x 10-5), and GSEA-SNP identified 9 gene sets (normalized enrichment score > 3.0) with 253 leading edge genes. Network analysis identified TNF (tumor necrosis factor), estrogen, and TP53 (tumor protein 53) as the top of 671 upstream regulators (p < 0.001), whereas the SOX2 (SRY [sex determining region Y]-box 2) and OCT4 (octamer-binding transcription factor 4) complex was the top master regulator out of 773 master regulators associated with fertility (p < 0.001). Identification of QTL and genes in pathways that improve early pregnancy success provides critical information for genomic selection to increase fertility in cattle. The identified genes and regulators also provide insight into the complex biological mechanisms underlying pregnancy establishment in cattle.
不育和亚生育能力对奶牛的经济效益和繁殖性能产生负面影响。值得注意的是，奶牛在怀孕的第一个月会出现显著的妊娠丢失，但对于影响奶牛妊娠成功和丢失的基因位点却知之甚少。为了鉴定与早期妊娠丢失相关的具有重大影响的数量性状位点（QTL），将安格斯杂交小母牛根据第28天的妊娠结局进行分类，用于连续胚胎移植。进行了全基因组关联分析（GWAA），比较了30头高生育力且妊娠成功率达100%的小母牛和55头亚生育力且妊娠成功率为25%或更低的小母牛。进行了基因集富集分析SNP（GSEA-SNP），以鉴定影响妊娠丢失的基因集和前沿基因。GWAA鉴定出22个QTL（p < 1 x 10-5），GSEA-SNP鉴定出9个基因集（标准化富集分数> 3.0）以及253个前沿基因。网络分析确定肿瘤坏死因子（TNF）、雌激素和肿瘤蛋白53（TP53）为671个上游调节因子中的前几位（p < 0.001），而SRY（性别决定区Y）-盒2（SOX2）和八聚体结合转录因子4（OCT4）复合体是与生育力相关的773个主要调节因子中的首要调节因子（p < 0.001）。鉴定出改善早期妊娠成功途径中的QTL和基因，为通过基因组选择提高奶牛生育力提供了关键信息。所鉴定的基因和调节因子也为奶牛妊娠建立的复杂生物学机制提供了见解。
