Modulation of the maternal immune system by the pre-implantation embryo

Walker, Caroline; Meier, S.; Littlejohn, Mathew D; Lehnert, Klaus; Roche, J.R.; Mitchell, Murray D.

doi:10.1186/1471-2164-11-474

Cited by 123 publications

(154 citation statements)

References 72 publications

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“…This suggests that the transcriptomic alterations that occur in the endometrium as time from estrous to the luteal phase progresses, occur in a similar manner irrespective of whether an embryo/conceptus is present. In addition, the majority of these genes are also involved in the classical Type I IFN response and are comparable to those identified by Walker et al [33] on Day 17 of pregnancy. Comparison of these DEGs with previous studies during the peri-implantation period of pregnancy revealed that 27 are differentially expressed on Day 16 as part of the early endometrial response to the conceptus (aconitase 2, mitochondrial; ACO2, beta-2-microglobulin; B2M, XIAP associated factor 1; BIRC4BP, C4A, C14orf10, CD81, C1R, CLDN4, eukaryotic translation initiation factor 4E; EIF4E, epithelial stromal interaction 1 (breast); EPSTI1, interferon, alphainducible protein 6; IFI6, GABA(A) receptor-associated protein like 1; GABARAPL1, ISG15, interferon regulatory factor 9; IRF9, RNA helicase LGP2; LGP2, LGALS9, LGALS3BP, MX2, MX1, OAS1, proteasome (prosome, macropain) inhibitor subunit 1 (PI31); PSMF1, receptor (chemosensory) transporter protein 4; RTP4, signal transducer and activator of transcription 1, 91kDa; STAT1, SCOTIN, UBE1L and tryptophanyl-tRNA synthetase; WARS [32]) and may represent early endometrial markers of a viable pre-implantation conceptus.…”

Section: Pregnancy Changessupporting

confidence: 64%

“…prior to pregnancy recognition [12,13]. The fact that little detectable differences can be determined between pregnant and cyclic endometria prior to Day 15 [33,34], means that alterations to cyclic endometria associated with different models of pregnancy outcome, can be exploited. One of the key factors that can modulate these temporal changes is circulating concentrations of progesterone.…”

Section: Cycle Related Changesmentioning

confidence: 99%

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Transcriptomic Analysis of the Bovine Endometrium: What is Required to Establish Uterine Receptivity to Implantation in Cattle ?

2012

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Abstract. In cattle, the majority of pregnancy loss can be attributed to early embryonic loss which occurs prior maternal recognition of pregnancy on Day 16 (Day 0 = ovulation). During this time, carefully orchestrated spatio-temporal alterations in the transcriptomic profile of the endometrium are required to drive conceptus elongation, via secretions from the endometrium (termed histotroph) and establish uterine receptivity to implantation. The two main modulators of these processed are progesterone (P4) and the pregnancy recognition signal interferon tau (IFNT). Altered concentrations of P4 in circulation mediate its effects via the endometrium and have been associated with different rates of conceptus elongation in cattle. Transcriptomic analysis of the endometrium has shown that modulation of circulating P4 alters endometrial expression of genes that can contribute to histotroph composition, which is beneficial (when P4 is supplemented) or detrimental (when P4 is reduced) to the developing conceptus. In addition, down-regulation of the progesterone receptor, required to establish uterine receptivity, is altered in the endometrium of heifers with altered P4 concentrations. IFNT, a type 1 interferon, also significantly impacts on the endometrial transcriptome. It induces the expression of a large number of classical interferon stimulated genes as early as Day 15 of pregnancy. In summary, the successful establishment of pregnancy in cattle requires a sequence of key events to ensure appropriate maternally derived secretions, establish uterine receptivity to implantation as well as an adequate endometrial response to IFNT production. Key words: Estrous cycle, Gene expression, Pregnancy, Progesterone (J. Reprod. Dev. 58: [189][190][191][192][193][194][195] 2012) I n cattle, as in other ungulate ruminants, the implantation process is characterized by a protracted period of elongation of the hatched blastocyst followed by apposition, attachment and adhesion of the trophectoderm to the uterine luminal epithelium (LE) [1,2]. Following successful fertilisation of an oocyte in the oviduct, the resulting embryo enters the uterus on approximately day 4 of pregnancy where it undergoes a number of cell divisions to form the morula which, after further differentiation, forms a blastocyst consisting of the inner cells mass (which will eventually give rise to the embryo/foetus) and an outer cell mass consisting of trophectoderm cells which ultimately give rise to the placenta. Up to the blastocyst stage of development, the embryo is relatively autonomous i.e. contact with the maternal uterine environment is not strictly required, as evidenced by the fact it is possible to culture embryos in vitro up to the blastocyst stage of development. However, once the embryo hatches from the zona pellucida (approximately day 9-10), significant morphological changes occur in the conceptus of domestic animals, including cattle, that differentiate the early pregnancy events from those of rodents, humans and non-human primates. The hatch...

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Section: Pregnancy Changessupporting

confidence: 64%

Section: Cycle Related Changesmentioning

confidence: 99%

Transcriptomic Analysis of the Bovine Endometrium: What is Required to Establish Uterine Receptivity to Implantation in Cattle ?

2012

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“…Moreover, SOCS1 and SOCS3 transcript levels rose specifically at the time of implantation. This regulation of endometrial SOCS mRNA expression by the conceptus is consistent with microarray studies that listed several differentially expressed SOCS genes in the bovine pregnant endometrium compared with cyclic tissue collected at day 17 (SOCS1, Walker et al 2010), day 18 (SOCS1, SOCS3, SOCS4, SOCS6, Bauersachs et al 2012) and day 20 (SOCS6, Mansouri-Attia et al 2009a) after oestrus. Interestingly, the expression patterns of CISH, SOCS1, SOCS2 and SOCS3 mRNA reported in this study are similar to the changes observed in the ovine endometrium (Sandra et al 2005).…”

Section: Luminal Epitheliumsupporting

confidence: 65%

“…ICAR areas contain endometrial glands whose presence is critical for conceptus elongation (Gray et al 2001(Gray et al , 2002. Recent high-throughput data have highlighted specific molecular pathways and genes that account for the biological functions related with each endometrial area (Mansouri-Attia et al 2009a, Walker et al 2010.…”

mentioning

confidence: 99%

SOCS genes expression during physiological and perturbed implantation in bovine endometrium

Carvalho¹,

Reinaud²,

Forde³

et al. 2014

Reproduction

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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

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“…Similarly, WARS mRNA expression increases 2.4-fold in the endometrium of pregnant cows on day 17 compared with the matching stage of the oestrous cycle (Walker et al 2010). Up-regulation of WARS protein expression observed in sheep endometrium at conceptus implantation had not been reported previously.…”

Section: Protein Synthesis and Degradationmentioning

confidence: 66%

Proteomic analysis of the sheep caruncular and intercaruncular endometrium reveals changes in functional proteins crucial for the establishment of pregnancy

Al-Gubory¹,

Arianmanesh²,

Garrel³

et al. 2014

Reproduction

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The expression and regulation of endometrial proteins are crucial for conceptus implantation and development. However, little is known about site-specific proteome profiles of the mammalian endometrium during the peri-implantation period. We utilised a two-dimensional gel electrophoresis/mass spectrometry-based proteomics approach to compare and identify differentially expressed proteins in sheep endometrium. Caruncular and intercaruncular endometrium were collected on days 12 (C12) and 16 (C16) of the oestrous cycle and at three stages of pregnancy corresponding to conceptus pre-attachment (P12), implantation (P16) and post-implantation (P20). Abundance and localisation changes in differentially expressed proteins were determined by western blot and immunohistochemistry. In caruncular endometrium, 45 protein spots (5% of total spots) altered between day 12 of pregnancy (P12) and P16 while 85 protein spots (10% of total spots) were differentially expressed between P16 and C16. In intercaruncular endometrium, 31 protein spots (2% of total spots) were different between P12 and P16 while 44 protein spots (4% of total spots) showed differential expression between C12 and C16. The pattern of protein changes between caruncle and intercaruncle sites was markedly different. Among the protein spots with implantation-related changes in volume, 11 proteins in the caruncular endometrium and six proteins in the intercaruncular endometrium, with different functions such as protein synthesis and degradation, antioxidant defence, cell structural integrity, adhesion and signal transduction, were identified. Our findings highlight the different but important roles of the caruncular and intercaruncular proteins during early pregnancy.

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Modulation of the maternal immune system by the pre-implantation embryo

Cited by 123 publications

References 72 publications

Transcriptomic Analysis of the Bovine Endometrium: What is Required to Establish Uterine Receptivity to Implantation in Cattle ?

Transcriptomic Analysis of the Bovine Endometrium: What is Required to Establish Uterine Receptivity to Implantation in Cattle ?

SOCS genes expression during physiological and perturbed implantation in bovine endometrium

Proteomic analysis of the sheep caruncular and intercaruncular endometrium reveals changes in functional proteins crucial for the establishment of pregnancy

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