Differential expression of T helper cytokines in the liver during early pregnancy in sheep

Yang, Ling; Bai, Jiachen; Zhao, Zimo; Li, Ning; Wang, Yujiao; Zhang, Leying

doi:10.21451/1984-3143-ar2018-0141

Cited by 14 publications

(14 citation statements)

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“…The conceptus and other endocrine mediators, including progesterone, actively shape the maternal immune response during early pregnancy to facilitate growth and development of a functional placenta (Ott et al., 2014). In sheep and cattle, the conceptus produces cytokines and chemokines that modulate the maternal immune system (Hansen, 2011; Yang et al., 2019). By influence of the conceptus and progesterone, there is shift of cytokine‐production profile from T helper 1 (Th1) to Th2 in maternal endometrium in ruminants (Hansen, 2011; Zhang et al., 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Th1 cytokines are implicated in the cellular immune process, proinflammatory responses and autoimmune responses. Th2 cytokines , such as IL‐4, IL‐5, IL‐6 and IL‐10, are essential for antibody‐mediated immune response (Ott & Gifford, 2010; Yang et al., 2019). The implication of miRNA, possibly exchanged by EVs, on maternal immunological status is yet to be determinate.…”

Section: Discussionmentioning

confidence: 99%

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Proteomic profile of pre‐implantational ovine embryos produced in vivo

Sanchez

Vasconcelos

Teles-Filho

et al. 2021

Reprod Domestic Animals

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The present study was conducted to decipher the proteome of in vivo‐produced pre‐implantation ovine embryos. Ten locally adapted Morana Nova ewes received hormonal treatment and were inseminated 12 hr after ovulation. Six days later, 54 embryos (morula and blastocyst developmental state) were recovered from eight ewes and pooled to obtain sufficient protein for proteomic analysis. Extracted embryo proteins were analysed by LC‐MS/MS, followed by identification based on four database searches (PEAKS, Proteome Discoverer software, SearchGUI software, PepExplorer). Identified proteins were analysed for gene ontology terms, protein clusters and interactions. Genes associated with the ovine embryo proteome were screened for miRNA targets using data sets of TargetScan (http://www.targetscan.org) and mIRBase (http://www.mirbase.org) servers. There were 667 proteins identified in the ovine embryos. Biological processes of such proteins were mainly related to cellular process and regulation, and molecular functions, to binding and catalytic activity. Analysis of the embryo proteins revealed 49 enriched functional clusters, linked to energy metabolism (TCA cycle, pyruvate and glycolysis metabolism), zona pellucida (ZP), MAPK signalling pathway, tight junction, binding of sperm to ZP, translation, proteasome, cell cycle and calcium/phospholipid binding. Sixteen miRNAs were related to 25 pre‐implantation ovine embryo genes, all conserved in human, bovine and ovine species. The interaction network generated by miRNet showed four key miRNAs (hsa‐mir‐106b‐5p; hsa‐mir‐30‐5p; hsa‐mir‐103a‐5p and hsa‐mir‐106a‐5p) with potential interactions with embryo‐expressed genes. Functional analysis of the network indicated that miRNAs modulate genes related to cell cycle, regulation of stem cell and embryonic cell differentiation, among others. Retrieved miRNAs also modulate the expression of genes involved in cell signalling pathways, such as MAPK, Wnt, TGF‐beta, p53 and Toll‐like receptor. The current study describes the first major proteomic profile of 6‐day‐old ovine embryos produced in vivo, setting a comprehensive foundation for our understanding of embryo physiology in the ovine species.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteomic profile of pre‐implantational ovine embryos produced in vivo

Sanchez

Vasconcelos

Teles-Filho

et al. 2021

Reprod Domestic Animals

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“…TLRs are implicated in immune regulation at the maternal-fetal interface during early pregnancy in ewes (Kaya et al 2017), and early pregnancy modulates the expression of TLRs in the CL and thymus in ewes (Atli et al 2018;Li et al 2020). It has been reported that there are changes in the expression of progesterone receptor, T helper cytokines, PG synthases, ISGs, melatonin receptor 1, cluster of differentiation 4, and gonadotropin releasing hormone and its receptor in the liver during early pregnancy in sheep (Zhang et al 2019;Yang et al 2019a;Bai et al 2020;Cao et al 2021). In this study, our results showed for the first time that early pregnancy modulates TLR signaling in the maternal liver.…”

Section: Discussionmentioning

confidence: 99%

“…Maternal metabolic demands induce a conspicuous change in maternal liver growth and the gene expression profile during pregnancy in rats (Bustamante et al 2010). We recently reported that progesterone receptor, progesterone-induced blocking factor (Zhang et al 2019), cyclooxygenase-2, prostaglandin (PG) E synthase, PGF synthase (Yang et al 2020a), ISGs (Yang et al 2020b), interleukin (IL)-5 (Yang et al 2019a) and gonadotropin releasing hormone and receptor (Cao et al 2021) are upregulated in the ovine maternal liver during early pregnancy. Furthermore, the protein levels of melatonin receptor 1 and cluster of differentiation 4 are increased in the liver during early pregnancy in sheep (Bai et al 2020).…”

Section: Introductionmentioning

confidence: 99%

The early stage of pregnancy modulates toll-like receptor signaling in the ovine liver

Gao

Cai

Han

et al. 2021

Journal of Applied Animal Research

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Toll-like receptors (TLRs) participate in maternal immune regulation at multiple maternal-fetal interfaces. The liver is crucial for innate and adaptive immunity during pregnancy. The objective of this study was to measure the expression of genes and proteins related to TLR signaling. In this study, livers were obtained from ewes on day 16 of the estrous cycle, and on days 13, 16 and 25 of gestation, and RT-qPCR, western blot and immunohistochemistry were employed to measure the expression of genes and proteins related to TLR signaling, including TLR2, TLR3, TLR4, TLR5, TLR7, TLR9, myeloid differentiation primary-response protein 88 (MyD88), tumor necrosis factor receptor associated factor 6 (TRAF6) and interleukin-1receptor-associated kinase 1 (IRAK1). Our data showed that the expression levels of TLR2, TLR3, TLR5, TLR9 and TRAF6 were increased, but those of TLR4 and TLR7 were decreased in the liver during early pregnancy. In addition, the expression levels of MyD88 and IRAK1 were the highest on days 13 and 16 of pregnancy, respectively, and the MyD88 protein was located in endothelial cells of proper hepatic arteries and portal veins and in hepatocytes. In conclusion, early pregnancy modulates TLR signaling in the maternal liver in sheep, which may participate in maternal immune regulation.

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“…Extensive changes occur in gene expression of pregnant animals' cells, especially ISGs and immune response-related genes (Bauersachs et al, 2006;Walker et al, 2010). Pregnant ewes had a higher expression of ISGs in the thymus (Zhang et al, 2020), higher expression of IL5, and a lower expression of IFNG, IL2, IL4, IL6, and IL10 in the liver (Yang et al, 2019). The expression of anti-inflammatory factors, such as IL10 and transforming growth factor-beta (TGFB) and pro-inflammatory like TNFA, were reported in endometrial and immune cells in cows (Rashid et al, 2018;Shirasuna et al, 2012;Talukder et al, 2017).…”

Section: Immunological Changes During Maternal Recognition Of Pregnancymentioning

confidence: 99%

Possible impact of neutrophils on immune responses during early pregnancy in ruminants

et al. 2021

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The interaction between early embryo and maternal immune system for the establishment of pregnancy is the focus of several studies; however, it remains unclear. The maternal immune response needs to keep a balance between avoiding any damage to the conceptus and maintaining its function in combating microbes as well. When conceptus-maternal crosstalk cannot achieve this balance, pregnancy losses might occur. Intercommunication between mother and conceptus is fundamental during early pregnancy to dictate the outcome of pregnancy. In ruminants, the embryo reacts with the maternal system mainly via interferon tau (IFNT) release. IFNT can act locally on the embryo and endometrial cells and systemically in several tissues and cells to regulate their response via the expression of interferon-stimulated genes (ISGs). Also, IFNT can induce the expression of inflammatory-related genes in immune cells. Day 7 embryo induces a shift in the maternal immune response towards anti-inflammatory (Th2) immune responses. During maternal recognition of pregnancy, peripheral mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) express markers that configure an anti-inflammatory response. However, PMNs response is more sensitive to the effects of IFNT. PMNs are more likely to express interferon-stimulated genes (ISGs), transforming growth factor-beta (TGFB), interleukin 10 (IL10), and arginase-1 (ARG1), configuring one of the most rapid immune responses to early pregnancy. This review focus on the local and peripheral immune responses during early pregnancy in ruminants, mainly the PMNs function in the immune system.

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Differential expression of T helper cytokines in the liver during early pregnancy in sheep

Cited by 14 publications

References 53 publications

Proteomic profile of pre‐implantational ovine embryos produced in vivo

Proteomic profile of pre‐implantational ovine embryos produced in vivo

The early stage of pregnancy modulates toll-like receptor signaling in the ovine liver

Possible impact of neutrophils on immune responses during early pregnancy in ruminants

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