Effects of Low Progesterone on the Endometrial Transcriptome in Cattle
Effects of Low Progesterone on the Endometrial Transcriptome in Cattle
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DOI：
10.1095/biolreprod.112.103424
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发表时间：
2012-11-01
影响因子：
3.6
通讯作者：
Lonergan, Pat
中科院分区：
文献类型：
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作者：
Forde, Niamh;Mehta, Jai P.;Lonergan, Pat
本研究的目的是确定低孕酮（P4）如何影响子宫内膜转录组，特别强调那些可能影响妊娠延长的变化。在进行发情同步和检测（发情=第0天，n = 40）后，将母牛随机分为对照组（n = 12）和低P4组（n = 28）。低P4组犊牛P4浓度持续低于对照组（P < 0.05）。子宫内膜基因表达的微阵列分析显示，低P4在第7天改变了498个差异表达基因（deg， 215个上调，283个下调）的表达，在第13天改变了351个差异表达基因（272个上调，79个下调）的表达。两组在第7天和第13天之间发生的时间变化数量相似（P4正常的母牛为2212，而P4低的母牛为2247）；其中1278个基因为两组共有。受高或低P4影响的deg数量在天内几乎没有重叠。将正常发情周期进程（即从第7天到第13天）与P4改变影响的时间变化进行比较，发现P4升高（4157）和降低（809）单独调节了大量基因。通过实时荧光定量PCR和原位杂交对所选基因进行分析发现，与第7天相比，MEP1B、NID2和PRSS23的表达在第13天有所增加（P < 0.05），而低P4的母牛的表达量与对照组相比显著降低。MEP1B主要定位于浅腺上皮和深腺上皮（GE）， NID2定位于深腺上皮，而PRSS23仅定位于管腔上皮。总之，我们利用一种独特的动物模型，确定了体内黄体P4输出减少所诱导的子宫内膜转录组的全局变化。将这些数据与排卵后P4补充或升高的先前数据结合起来，我们已经确定了一组基因，这些基因在子宫内膜中通过体内循环P4浓度进行真正的调节，并可能影响受孕延长。
The objective of the present study was to determine how low progesterone (P4) affects the endometrial transcriptome, with specific emphasis on those changes that may impact conceptus elongation. Following estrous synchronization and detection (estrus = Day 0, n = 40), heifers were randomly assigned to a control group (n = 12) or a low P4 group (n = 28). Heifers in the low P4 group had consistently lower P4 concentrations compared to controls (P < 0.05). Microarray analysis of endometrial gene expression revealed low P4 altered the expression of 498 differentially expressed genes (DEGs; 215 up-and 283 down-regulated) on Day 7 and 351 DEGs (272 up- and 79 down-regulated) on Day 13. A similar number of temporal changes occurred between Day 7 and Day 13 in both groups (2212 in heifers with normal P4 compared with 2247 in heifers with low P4); of these DEGs, 1278 were common to both groups. Little overlap in the number of DEGs affected by high or low P4 was observed across days. Comparison of the temporal changes that occur during normal estrous cycle progression (i.e., from Day 7 to Day 13) to those affected by altered P4 found significant numbers of genes were modulated by elevated (4157) and decreased (809) P4 alone. Analysis of selected genes by quantitative real-time PCR and in situ hybridization revealed that expression of MEP1B, NID2, and PRSS23 increased on Day 13 compared to Day 7 (P < 0.05) and that the magnitude of increase was significantly diminished in heifers with low P4 compared to controls. MEP1B predominantly localized to the both the superficial and deep glandular epithelium (GE), NID2 localized to the deep GE, whereas PRSS23 localized only to the luminal epithelium. In conclusion, we have determined the global changes in the endometrial transcriptome induced by decreasing the output of P4 from the corpus luteum in vivo using a unique animal model. Placing these data into context with previous data in which P4 was supplemented or elevated after ovulation, we have identified a panel of genes that are truly regulated in the endometrium by circulating concentrations of P4 in vivo and that likely impact conceptus elongation.