Progesterone receptor-dependent regulation of genes in the oviducts of female mice
Progesterone receptor-dependent regulation of genes in the oviducts of female mice
复制标题
DOI：
10.1152/physiolgenomics.00044.2014
复制
发表时间：
2014-08-15
影响因子：
4.6
通讯作者：
Robker, Rebecca L.
中科院分区：
文献类型：
--
作者：
Akison, Lisa K.;Boden, Michael J.;Robker, Rebecca L.
输卵管在配子和胚胎运输以及支持早期胚胎发育中起关键作用。孕激素受体（PGR）是一种在输卵管细胞中高度表达的转录因子，而其激活配体孕酮在排卵临近时激增至峰值水平。已知孕酮在体外调节输卵管纤毛跳动和肌肉收缩，但对PGR如何在体内介导这一点知之甚少。我们使用PCR无效小鼠来鉴定在排卵期输卵管中可能受PCR调控的基因。组织学上，与正常同窝小鼠相比，PGR基因敲除小鼠的输卵管没有明显的结构或形态缺陷。然而，人类绒毛膜促性腺激素后8小时的输卵管微阵列分析显示> 1，000个PGR依赖基因。利用逆转录聚合酶链反应（RT-PCR），我们选择了10个基因进行验证的基础上，他们在卵母细胞/胚胎运输和支持的潜在作用。8个基因被证实是下调（Adamts1，Itga8，Edn3，Prlr，Ptgfr，Des，Myocd和Actg2）和一个上调（Agtr2）在PCR无效输卵管。这些基因的表达也进行了评估，在排卵和妊娠第1天和第4天的自然周期小鼠的输卵管。Adamts1，Itga8，Edn3，Prlr和Ptgfr在排卵/交配时在输卵管中显著上调。然而，大多数基因在其他时间表现出基础水平的表达。例外情况是Prlr和Ptgfr，在妊娠第1天和/或第4天呈脉冲性增加。这是第一个，全面的研究，以阐明推定的PGR调控基因在输卵管，并揭示了关键的下游目标可能介导卵母细胞和胚胎运输。
Oviducts play a critical role in gamete and embryo transport, as well as supporting early embryo development. Progesterone receptor (PGR) is a transcription factor highly expressed in oviductal cells, while its activating ligand, progesterone, surges to peak levels as ovulation approaches. Progesterone is known to regulate oviduct cilia beating and muscular contractions in vitro, but how PGR may mediate this in vivo is poorly understood. We used PGR null mice to identify genes potentially regulated by PGR in the oviducts during the periovulatory period. Histologically, oviducts from PGR null mice showed no gross structural or morphological defects compared with normal littermates. However, microarray analysis of oviducts at 8 h posthuman chorionic gonadotropin revealed > 1,000 PGR-dependent genes. Using reverse-transcription polymerase chain reaction (RT-PCR) we selected 10 genes for validation based on their potential roles in oocyte/embryo transport and support. Eight genes were confirmed to be downregulated (Adamts1, Itga8, Edn3, Prlr, Ptgfr, Des, Myocd, and Actg2) and one upregulated (Agtr2) in PGR null oviducts. Expression of these genes was also assessed in oviducts of naturally cycling mice during ovulation and day 1 and day 4 of pregnancy. Adamts1, Itga8, Edn3, Prlr, and Ptgfr were significantly upregulated in oviducts at ovulation/mating. However, most genes showed basal levels of expression at other times. The exceptions were Prlr and Ptgfr, which showed pulsatile increases on day 1 and/or day 4 of pregnancy. This is the first, comprehensive study to elucidate putative PGR-regulated genes in the oviduct and reveals key downstream targets potentially mediating oocyte and embryo transport.