Suppressor of cytokine signalling (SOCS) genes are expressed in the endometrium and regulated by conceptus signals during early pregnancy in the ewe

Abstract

It is established that the conceptus-endometrium dialogue involves cytokines, growth factors and hormones. Given the crucial functions of the suppressor of cytokine signaling (SOCS) family proteins in cytokine signalling, we analyzed the expression and the regulation of CIS and SOCSs 1-3 transcripts during early pregnancy in the ovine endometrium. An overall stimulation of the SOCS transcripts was described in the pregnant ewes with two specific patterns. Unilaterally pregnant ewes confirmed the conceptus-produced factors as regulators of the SOCSs 1-3 expression at day 16 of pregnancy. Intrauterine injection of recombinant ovine interferon (IFN ) in cyclic ewes stimulated the expression of the SOCS mRNA with various potencies, therefore suggesting that the SOCS could take part in the negative regulation of the IFN signalling pathway.

Genes involved in conceptus–endometrial interactions in ruminants: insights from reductionism and thoughts on holistic approaches

“…Since expression of ISGs increases in a stage-specific manner within endometria of diverse species, including domestic animals, laboratory rodents, primates, and humans during early pregnancy, they may be universally important in establishment of uterine receptivity to conceptus implantation (Li et al 2001, Austin et al 2003, Cheon et al 2003, Bany & Cross 2006, Hess et al 2007, Kashiwagi et al 2007. A number of transcriptional profiling experiments conducted with human cells, ovine endometrium, and bovine endometrium have elucidated genes regulated by IFNT during pregnancy (Kim et al 2003, Sandra et al 2005, Chen et al 2006, Gray et al 2006, Klein et al 2006; see Supplementary Table 1 and Figs 1 and 2 for summary and interpretation).…”

“…In fact, all components of the ISGF3 transcription factor complex (STAT1, STAT2, and IRF9) and other classical ISGs (B2M, GBP2, IFI27, IFIT1, ISG15, MIC, and OAS) contain one or more ISREs in their promoters. Further, suppressor of cytokine signaling (SOCS1-3) are also upregulated in endometria by pregnancy and IFNT (Sandra et al 2005). Depending on their cell-specific expression in the uterus, SOCS1-3 may be involved in negative regulation of the JAK-STAT pathway activated by IFNT (Kile et al 2002).…”

SOCS genes expression during physiological and perturbed implantation in bovine endometrium

“…Although the contribution/function of various endometrial factors (ligands, receptors and effectors) in the control of implantation has been unveiled based on descriptive and functional studies, few publications have focused on the regulation of SOCS genes and their biological functions in the uterus (Sandra et al 2005, Oliveira et al 2012. In order to provide new insights into the involvement of SOCS in endometrial physiology, a comprehensive analysis of known SOCS (CISH, SOCS1-7) gene expression profiles was carried out in bovine endometrium in order to i) establish mRNA expression patterns of the SOCS gene family during the oestrous cycle and early pregnancy, ii) determine the cellular localisation of SOCS3 and SOCS6 protein during the oestrous cycle and early pregnancy, iii) define the contribution of IFNT and of P 4 in the regulation of the SOCS genes and iv) determine if endometrial SOCS mRNA levels are altered in a model of compromised pregnancy using bovine SCNT concepti.…”

“…At day 14 after oestrus, recombinant ovine IFNT (roIFNT; 200 mg/ml, 25 ml/horn; Sandra et al 2005) or control solution (saline buffer) was infused into the uterine lumen, as previously reported (Forde et al 2011a, Eozenou et al 2012. The cows were slaughtered 2 h after the intra-uterine infusion and the endometrium of five IFNT-infused and five control cows was collected, dissected and stored as described in Experiment 2.…”

“…The members of the SOCS family have been identified in numerous vertebrate and some invertebrate species (DelgadoOrtega et al 2013) and are involved in the control of many biological processes and physiological functions including pregnancy (Yoshimura et al 2007, Fitzgerald et al 2009). In the context of the uterus, SOCS1 and SOCS3 have been shown to contribute to decidualisation and uterine receptivity in the human (Dimitriadis et al 2006, Aghajanova et al 2009) and in the sheep, the endometrial expression of CISH, SOCS1, SOCS2 and SOCS3 transcripts has been reported to be affected by the presence of the conceptus (Sandra et al 2005). Nevertheless, these data are scattered and fail to provide a comprehensive view of how SOCS factors take part in the regulation of endometrial physiology in mammals.…”