Progesterone-Regulated Changes in Endometrial Gene Expression Contribute to Advanced Conceptus Development in Cattle

Progesterone-Regulated Changes in Endometrial Gene Expression Contribute to Advanced Conceptus Development in Cattle
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DOI:
10.1095/biolreprod.108.074336
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发表时间:
2009-10-01
影响因子:
3.6
通讯作者:
Roche, J. F.
Roche, J. F.
中科院分区:
生物学2区
文献类型:
--
作者:
Forde, N.;Carter, F.;Roche, J. F.

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排卵后循环孕酮(P4)浓度升高与肉牛和奶牛妊娠成功率增加有关。我们的研究目的是确定P4升高如何改变子宫内膜基因表达以促进妊娠发展。同步母牛进行人工授精(第0天),随机分为妊娠P4高组和妊娠P4正常组。所有高P4组在人工授精后第3天使用阴道内释放P4装置,P4浓度升高至第7天(P < 0.05)。在妊娠第5、7、13或16天收集组织,使用牛Affymetrix (Santa Clara, CA)微阵列分析子宫内膜基因表达。微阵列分析表明,P4调控基因数量最多的日子恰好是P4基因谱差异最长的日子。倍数变化增加最大的基因(如DGAT2和MSTN[也称为GDF8])与甘油三酯合成和葡萄糖运输有关,可作为胚胎发育的能量来源。时间变化发生在妊娠早期的不同阶段,最大的差异发生在分离良好的妊娠发展阶段。通过实时荧光定量PCR对多个基因的验证表明,P4的补充通过改变与组织细胞组成有关的基因表达模式的时间(FABP、DGAT2和MSTN)或持续时间(CRYGS)来促进子宫内膜基因的表达。
The postovulatory rise in circulating progesterone (P4) concentrations is associated with increased pregnancy success in beef and dairy cattle. Our study objective was to determine how elevated P4 alters endometrial gene expression to advance conceptus development. Synchronized heifers were inseminated (Day 0) and randomly assigned to pregnant high P4 or to pregnant normal P4. All high P4 groups received a P4-release intravaginal device on Day 3 after insemination that increased P4 concentrations up to Day 7 (P < 0.05). Tissue was collected on Day 5, 7, 13, or 16 of pregnancy, and endometrial gene expression was analyzed using the bovine Affymetrix (Santa Clara, CA) microarrays. Microarray analyses demonstrated that the largest number of P4-regulated genes coincided with the day when the P4 profiles were different for the longest period. Genes with the largest fold change increase (such as DGAT2 and MSTN [also known as GDF8]) were associated with triglyceride synthesis and glucose transport, which can be utilized as an energy source for the developing embryo. Temporal changes occurred at different stages of early pregnancy, with the greatest difference occurring between well-separated stages of conceptus development. Validation of a number of genes by quantitative real-time PCR indicated that P4 supplementation advances endometrial gene expression by altering the time (FABP, DGAT2, and MSTN) or duration (CRYGS) of expression pattern for genes that contribute to the composition of histotroph.