SOCS genes expression during physiological and perturbed implantation in bovine endometrium

Abstract

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.Free French abstract A French translation of this abstract is freely available at

Signal transducer and activator of transcription-3 licenses Toll-like receptor 4-dependent interleukin (IL)-6 and IL-8 production via IL-6 receptor-positive feedback in endometrial cells

“… 35 In cattle, SOCS3 expression increases during implantation, around day 20 of pregnancy, and is induced by interferon-τ, an important signaling cytokine during embryo recognition. 39 , 40 Therefore, balanced activation of the STAT/SOCS signaling pathway is essential for fertility. However, during uterine infection, TLR4 cross-talk with the IL6R pathway may perturb this balance and these concepts need to be explored further.…”

Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality

“…It harbors 5 miRNAs: Has-miR-550a-3p, Has-miR-335-3p, Has-miR-571, Has-miR-377-3p, Has-miR-105-5p. Interestingly, a huge literature argues that several mRNA targets work in important phases of embryo development: SOCS and FOX targets are spatio-temporally regulated in the endometrium, reflecting the acquisition of receptivity, maternal recognition of pregnancy and implantation [288,289]; YY2 is one of the major regulators of mouse embryonic stem cell self-renewal and lineage commitment [290] as well as the RNA methyltransferases NSUN4 is enriched in mouse tissues during embryo development [291]. Interestingly, NANOS1 has an essential role in the central nervous system development [292].…”

Maternal metabolism affects endometrial expression of oxidative stress and FOXL2 genes in cattle

“…In the ovine and bovine species, expression patterns of endometrial genes have been intensively investigated by our laboratory and others using in vitro and in vivo experimental models associated with high-throughput analyses and candidate gene approaches. Determining variations in gene expression during estrous cycle and early pregnancy allow a classification of endometrial genes in three major categories namely (i) conceptus regulated gene expression that involves IFNT, making these genes members of classical and non-classical interferon-regulated genes such as the STAT1-SOCS pathway thought to play critical functions during implantation in cattle [ 19 , 20 ], (ii) conceptus regulated and IFNT-independent expression that is modified by still unknown or already identified conceptus-produced factors (e. g. cortisol, prostaglandins [ 21 ]) such as SOCS6 [ 22 ] and PLET1 [ 23 ], two genes highly expressed in the luminal epithelial cells when apposition initiates, and (iii) expression that is not affected by the presence of the conceptus but is variable across the estrous cycle (e. g. under the influence of female hormones including ovarian steroids [ 16 , 24 , 25 ] such as the scavenger receptor SCARA5 [ 23 ], the key enzyme in prostaglandin biosynthesis PTGS2 [ 26 , 27 ], and FOXL2 , a key transcription factor of the ovary and recently characterized in the bovine endometrium [ 28 ]. These three categories of regulated genes contribute to endometrial receptivity, conceptus elongation and implantation and their perturbed expression may lead to detrimental effects on establishment, progression and outcome of pregnancy [ 13 ].…”

“…Caruncular endometrium is represented by small sparse aglandular structures, whereas intercaruncular endometrium contains endometrial glands the secretions of which are critical for conceptus elongation [ 35 ]. High-throughput data have highlighted that endometrial CAR and ICAR areas exhibit a site-specific response to the presence of the implanting conceptus in normal or perturbed pregnancies [ 22 , 23 , 28 , 36 – 38 ]. In this study, we used a novel model of age-matched pregnant primiparous postpartum lactating or non-lactating dairy cows combined with embryo transfer [ 39 ].…”