SOCS genes expression during physiological and perturbed implantation in bovine endometrium

SOCS genes expression during physiological and perturbed implantation in bovine endometrium
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DOI:
10.1530/rep-14-0214
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发表时间:
2014-12-01
期刊:
影响因子:
3.8
通讯作者:
Sandra, O.
Sandra, O.
中科院分区:
生物学3区
文献类型:
--
作者:
Carvalho, A. Vitorino;Reinaud, P.;Sandra, O.

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在哺乳动物中,细胞因子信号传导抑制因子(CISH,SOCS 1至SOCS 7)控制着参与调节包括妊娠在内的许多生理过程的信号传导途径。为了获得对SOCS在子宫内膜中的生物学功能的新认识,在牛的泪阜(CAR)和泪阜间(ICAR)组织中进行了SOCS基因表达的综合分析,所述组织收集于i)在发情周期期间,ii)在母体识别妊娠时和在授精雌性的着床时,iii)在发情后第14天子宫干扰素-tau(IFNT)输注后,iv)在一段时间的受控阴道内孕酮释放之后,和v)在通过体细胞核移植(SCNT)移植胚胎之后。IFNT对体外培养的上皮细胞和基质细胞的调节作用也进行了研究。总之,我们的数据表明,CISH,SOCS 4,SOCS 5和SOCS 7 mRNA水平在黄体溶解和妊娠期间受到的影响很小。相反,SOCS 1、SOCS 2、SOCS 3和SOCS 6 mRNA水平在着床时(妊娠第20天)强烈上调。体外和体内实验表明,只有CISH,SOCS 1,SOCS 2和SOCS 3是IFN诱导的基因。免疫组化显示SOCS 3和SOCS 6在妊娠子宫内膜的腔上皮、腺上皮和间质细胞的核中呈强阳性表达。最后,SOCS 3表达在SCNT妊娠中显著增加,这与先前在这种受损植入模型中报道的免疫功能改变一致。总的来说,我们的数据表明,子宫内膜SOCS基因表达的时空变化反映了获得的容受性,母亲识别怀孕和种植。
In mammals, suppressor of cytokine signalling (CISH, SOCS1 to SOCS7) factors control signalling pathways involved in the regulation of numerous physiological processes including pregnancy. In order to gain new insights into the biological functions of SOCS in the endometrium, a comprehensive analysis of SOCS gene expression was carried out in bovine caruncular (CAR) and intercaruncular (ICAR) tissues collected i) during the oestrous cycle, ii) at the time of maternal recognition of pregnancy and at implantation in inseminated females, iii) following uterine interferon-tau (IFNT) infusion at day 14 post-oestrus, iv) following a period of controlled intravaginal progesterone release and v) following transfer of embryos by somatic-cell nuclear transfer (SCNT). The regulatory effects of IFNT on in vitro cultured epithelial and stromal cells were also examined. Altogether, our data showed that CISH, SOCS4, SOCS5 and SOCS7 mRNA levels were poorly affected during luteolysis and pregnancy. In contrast, SOCS1, SOCS2, SOCS3 and SOCS6 mRNA levels were strongly up-regulated at implantation (day 20 of pregnancy). Experimental in vitro and in vivo models demonstrated that only CISH, SOCS1, SOCS2 and SOCS3 were IFNT-induced genes. Immunohistochemistry showed an intense SOCS3 and SOCS6 staining in the nucleus of luminal and glandular epithelium and of stromal cells of pregnant endometrium. Finally, SOCS3 expression was significantly increased in SCNT pregnancies in keeping with the altered immune function previously reported in this model of compromised implantation. Collectively, our data suggest that spatio-temporal changes in endometrial SOCS gene expression reflect the acquisition of receptivity, maternal recognition of pregnancy and implantation.