Pregnancy-induced changes in the transcriptome of the bovine corpus luteum during and after embryonic interferon-tau secretion

2021 ◽  
Author(s):  
Megan A Mezera ◽  
Wenli Li ◽  
Milo C Wiltbank
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Early Pregnancy ◽  
Practical Importance ◽  
Interferon Signaling ◽  
Interferon Tau ◽  
Interferon Stimulated Genes ◽  
Bovine Corpus Luteum ◽  
Major Alteration ◽  
Induced Changes

Abstract Understanding luteal maintenance during early pregnancy is of substantial biological and practical importance. Characterizing effects of early pregnancy, however, has historically been confounded by use of controls with potential exposure to early PGF pulses or differences in CL age. To avoid this, the present study utilized bihourly blood sampling to ensure control CL (n = 6) were of a similar age to CL from pregnant animals (n = 5), yet without exposure to PGF pulses. Additionally, CL from second month of pregnancy (n = 4) were analyzed to track fate of altered genes after cessation of embryonic interferon tau (IFNT) secretion. The major alteration in gene expression in first month of pregnancy occurred in interferon-stimulated genes (ISGs), with immune/interferon signaling pathways enriched in three independent over-representation analyses. Most ISGs decreased during second month of pregnancy, though, surprisingly, some ISGs remained elevated in the second month even after cessation of IFNT secretion. Investigation of luteolytic genes found few altered transcripts, in contrast to previous reports, likely due to removal of controls exposed to PGF pulses. An exception to this trend was decreased expression of transcription factor NR4A1. Beyond luteolytic genes and ISGs, over representation analyses highlighted the prevalence of altered genes within the extracellular matrix and regulation of IGF availability, confirming results of other studies independent of luteolytic genes. These results support the idea that CL maintenance in early pregnancy is related to lack of PGF exposure, although potential roles for CL expression of diverse ISGs and other pathways activated during early pregnancy remain undefined.

scholarly journals Expression of inter-alpha-trypsin inhibitor heavy chains in endometrium of cyclic and pregnant gilts

Reproduction ◽  
2003 ◽  
pp. 621-627 ◽  
Author(s):  
RD Geisert ◽  
MD Ashworth ◽  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Western Blot ◽  
Protease Inhibitor ◽  
Early Pregnancy ◽  
Trypsin Inhibitor ◽  
Serine Protease Inhibitor ◽  
Oestrous Cycle ◽  
Heavy Chains ◽  
Formation Of Complexes

Attachment of the placenta to the uterus in pigs involves extracellular interaction between the expanding trophoblastic membrane and the thick glycocalyx present on the uterine epithelial microvilli. Formation of complexes between members of inter-alpha-trypsin inhibitor family may function in the maintenance of the extracellular matrix. This study investigated the change in the inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3 and ITIH4) during the oestrous cycle and early pregnancy in pigs. Gene expression of ITIH1, ITIH2, ITIH3 and ITIH4 was detected in the endometrium of cyclic and pregnant gilts; however, gene expression of ITIH was not altered throughout the oestrous cycle or early pregnancy. Western blot analysis with an ITIH antiserum identified the possible linkage forms of ITIH with the serine protease inhibitor, bikunin. Pregnancy altered the release of the various inter-alpha-inhibitor forms from the endometrium during the period of trophoblastic attachment. The results from this study indicate that the inter-alpha-trypsin inhibitor family plays an important role in maintenance of the uterine surface glycocalyx during placental attachment in pigs.

scholarly journals Heat stress modulates polymorphonuclear cell response in early pregnancy cows: I. interferon pathway and oxidative stress

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257418
Author(s):  
Carolina dos Santos Amaral ◽  
Gabrielle Rebeca Everling Correa ◽  
Lady Katerine Serrano Mujica ◽  
Mariani Farias Fiorenza ◽  
Suzan Gonçalves Rosa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Heat Stress ◽  
Early Pregnancy ◽  
Interferon Tau ◽  
Altered Expression ◽  
Stress Group ◽  
Pathway Gene ◽  
Interferon Pathway ◽  
And Oxidative Stress

One of the major causes of early pregnancy loss is heat stress. In ruminants, interferon tau (IFNT) is the embryo signal to the mother. Once the interferon signaling pathway is activated, it drives gene expression for interferon-stimulated genes (ISGs) and alters neutrophils responses. The aim of the present study was to evaluate interferon (IFN) pathway, ISGs and gene expression in polymorphonuclear leukocytes (PMN) and oxidative stress in dairy cows under heat stress. Pregnant cows had their estrous cycle synchronized and randomly assigned to a comfort or heat stress group. Blood samples were collected at artificial insemination (AI) and on Days 10, 14 and 18 following AI. Pregnant cows were pregnancy checked by ultrasound on Day 30 and confirmed on Day 60 post-AI. Results are presented as mean ± SEM. The corpus luteum (CL) diameter was not different between groups of pregnant cows; concentration of progesterone of pregnant cows on Day 18 following AI was greater in comfort group compared to heat stressed group. Comfort pregnant cows had higher expression of all analyzed genes from interferon pathway, except for IFNAR1, on both Days 14 and 18. Conversely, heat stressed cows did not show altered expression of IFNT pathway genes and ISGs between Days 10, 14, and 18 after AI. The oxidative stress, determined as malondialdehyde (MDA) levels, was greater in heat stress group on Days 10, 14 and 18, independent of pregnancy status. Heat stress negatively influences expression of ISGs, IFN pathway gene expression in neutrophils, and oxidative stress. Our data suggest that lower conception rates in cows under heat stress are multifactorial, with the association of interferon pathway activation and the unbalanced oxidative stress being main contributing factors.

scholarly journals Global transcriptomic response of bovine endometrium to blastocyst-stage embryos

Reproduction ◽  
2019 ◽  
Vol 158 (3) ◽  
pp. 223-235 ◽  
Author(s):  
C Passaro ◽  
D Tutt ◽  
S Bagés-Arnal ◽  
C Maicas ◽  
R Laguna-Barraza ◽  
...  
Keyword(s):  
Rna Extraction ◽  
Transcript Abundance ◽  
Blastocyst Stage ◽  
Subsequent Pregnancy ◽  
Rna Seq ◽  
Interferon Tau ◽  
Transcriptomic Response ◽  
Interferon Stimulated Genes ◽  
Induced Changes

The aims of this study were (i) to investigate changes in the global transcriptome of bovine endometrial explants induced by exposure to blastocysts, (ii) to investigate if male and female blastocysts elicit a differential response in the endometrial transcriptome in vitro and (iii) to determine whether bovine endometrium responds to the presence of murine embryos. In Experiment 1, endometrial explants from the same uterus were cultured for 6 h with or without 20 in vitro-produced bovine blastocysts. In Experiment 2, endometrial explants were cultured with male or female bovine blastocysts produced in vitro by IVF either using sex-sorted semen or conventional unsorted semen followed by embryo sexing based on a biopsy. In Experiment 3, endometrial explants were cultured alone or in the presence of bovine blastocysts (n = 25) or murine blastocysts (n = 25). Following culture, explants were snap frozen and stored at −80°C until RNA extraction, qPCR or RNA-Seq. Culture with bovine blastocysts increased endometrial expression of 40 transcripts, all of which were interferon-tau induced. Culture with male or female bovine blastocysts increased transcript abundance of five classic interferon-stimulated genes (MX1, MX2, ISG15, OASY1, RSAD2) in explants; however, there was no difference in abundance of transcripts previously reported to be related to embryonic sex (IFNAR1, IFNAR2, CTGF, ARTN, SLC2A1, SLC2A5). Exposure to murine blastocysts did not elicit any detectable change in transcript abundance. These findings, coupled with our previous data, indicate that very local, interferon-tau-induced changes in endometrial gene expression occur in response to blastocysts; whether such changes play any role in subsequent pregnancy recognition remains to be established.

scholarly journals Interferon-tau promotes luteal endothelial cell survival and inhibits specific luteolytic genes in bovine corpus luteum

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. 559-568 ◽  
Author(s):  
Raghavendra Basavaraja ◽  
Emilia Przygrodzka ◽  
Bartosz Pawlinski ◽  
Zdzislaw Gajewski ◽  
Monika M Kaczmarek ◽  
...  
Keyword(s):  
Life Span ◽  
Cell Survival ◽  
Corpus Luteum ◽  
Luteal Cell ◽  
Interferon Tau ◽  
Interferon Stimulated Genes ◽  
Proliferative Effect ◽  
Domestic Ruminants ◽  
Prostaglandin F2a ◽  
Bovine Corpus Luteum

Interferon-tau (IFNT), a maternal recognition of pregnancy (MRP) signals in domestic ruminants, suppresses the release of luteolytic pulses of uterine prostaglandin F2a (PGF2a), thus extending the corpus luteum (CL) life span. We hypothesized that IFNT also exerts anti-luteolytic actions in bovine CL. To examine the direct effects of IFNT on bovine CL, luteal slices and enriched luteal endothelial cells (LECs) were utilized. We found that recombinant ovine IFNT (roIFNT) markedly elevates interferon-associated genes (STAT1, STAT2 and IRF9) and interferon-stimulated genes (ISGs: MX2, ISG15 and OAS1Y) in both models. Furthermore, IFNT time-dependently induced STAT1 phosphorylation in LECs without affecting total STAT1. roIFNT-stimulated viable LECs numbers and the knockdown of protein inhibitor of activated STAT1 (PIAS1) abolished this effect, suggesting that PIAS1 may mediate the proliferative effect of IFNT. IFNT significantly downregulated luteolytic genes such as TGFB1, thrombospondin-1 (THBS1), endothelin-1 (EDN1) and serpin family E member-1 (SERPINE1) in LECs. However, less robust effects were observed in luteal slices. Moreover, PGF2a alone induced THBS1, SERPINE1 and EDN1 mRNA in CL slices whereas in the presence of IFNT, THBS1 and SERPINE1 stimulation was abolished. Collectively, these results indicate that IFNT acts via STAT1- IRF9-dependent and independent pathways and affects diverse luteal functions. Most interestingly, this study suggests the existence of an anti-luteolytic effect of IFNT in bovine CL, namely, inhibiting key PGF2a-induced luteolytic genes. The proliferative effect of IFNT may constitute an additional mechanism that promotes luteal cell survival, thus, extending the luteal life span during early pregnancy in cows.

scholarly journals Early Pregnancy Induces Expression of STAT1, OAS1 and CXCL10 in Ovine Spleen

Animals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 882 ◽  
Author(s):  
Yujiao Wang ◽  
Xu Han ◽  
Leying Zhang ◽  
Nan Cao ◽  
Lidong Cao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Early Pregnancy ◽  
Oligoadenylate Synthetase ◽  
Interferon Tau ◽  
Interferon Stimulated Genes ◽  
Adaptive Immune ◽  
Ruminant Species ◽  
Immunohistochemistry Analysis ◽  
Stat1 Protein ◽  
Red Pulp

Interferon-tau is a maternal recognition factor in ruminant species, and spleen plays an essential role in regulating innate and adaptive immune responses. However, it is not fully understood that early pregnancy induces expression of interferon stimulated genes (ISGs) in the spleen during early pregnancy in ewes. In this study, spleens were collected from ewes at day 16 of the estrous cycle, and on days 13, 16, and 25 of gestation (n = 6 for each group), and RT-qPCR, western blot and immunohistochemistry analysis were used to detect the expression of signal transducer and activator of transcription 1 (STAT1), 2′,5′-oligoadenylate synthetase 1 (OAS1), myxovirusresistance protein 1 (Mx1) and C-X-C motif chemokine 10 (CXCL10). The results revealed that STAT1, OAS1 and CXCL10 mRNA and proteins were upregulated in the spleens during early pregnancy, and STAT1 protein was located in connective tissue cells in the capsule and trabeculae, and blood cells and lymphocytes in the red pulp. However, early pregnancy had no significant effects on expression of MX1 mRNA and protein. In conclusion, early pregnancy induces expression of STAT1, OAS1 and CXCL10 in maternal spleen, suggesting that maternal spleen is involved in immune regulation of pregnancy in sheep.

scholarly journals Blastocyst-induced changes in the bovine endometrial transcriptome

Reproduction ◽  
2018 ◽  
Vol 156 (3) ◽  
pp. 219-229 ◽  
Author(s):  
C Passaro ◽  
D Tutt ◽  
D J Mathew ◽  
J M Sanchez ◽  
J A Browne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Conditioned Medium ◽  
Direct Contact ◽  
Blastocyst Stage ◽  
Induced Responses ◽  
Interferon Stimulated Genes ◽  
Maternal Interaction ◽  
Induced Changes ◽  
Maximum Expression

The objectives of this study were (i) to determine whether blastocyst-induced responses in endometrial explants were detectable after 6- or 24-h co-culture in vitro; (ii) to test if direct contact is required between embryos and the endometrial surface in order to stimulate endometrial gene expression; (iii) to establish the number of blastocysts required to elicit a detectable endometrial response; (iv) to investigate if upregulation of five interferon-stimulated genes (ISGs) in the endometrium was specific to the blastocyst stage and (v) to test if alterations in endometrial gene expression can be induced by blastocyst-conditioned medium. Exposure of endometrial explants to Day 8 blastocysts in vitro for 6 or 24 h induced the expression of ISGs (MX1, MX2, OAS1, ISG15, RSAD2); expression of IFNAR1, IFNAR2, NFKB1, IL1B, STAT1, LGALS3BP, LGALS9, HPGD, PTGES, ITGB1, AKR1C4, AMD1 and AQP4 was not affected. Culture of explants in the presence of more than five blastocysts was sufficient to induce the effect, with maximum expression of ISGs occurring in the presence of 20 blastocysts. This effect was exclusive to blastocyst stage embryos; oocytes, 2-cell embryos or Day 5 morulae did not alter the relative abundance of any of the transcripts examined. Direct contact between blastocysts and the endometrial surface was not required in order to alter the abundance of these transcripts and blastocyst-conditioned medium alone was sufficient to stimulate a response. Results support the notion that local embryo–maternal interaction may occur as early as Day 8 of pregnancy in cattle.

scholarly journals Downregulated luteolytic pathways in the transcriptome of early pregnancy bovine corpus luteum are mimicked by interferon-tau in vitro

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Raghavendra Basavaraja ◽  
Jessica N. Drum ◽  
Jackson Sapuleni ◽  
Lonice Bibi ◽  
Gilgi Friedlander ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Sonic Hedgehog ◽  
Early Pregnancy ◽  
Interferon Tau ◽  
Bovine Corpus Luteum ◽  
Canonical Pathways ◽  
Transcriptomic Signature ◽  
Distinct Features

Abstract Background Maintenance of the corpus luteum (CL) beyond the time of luteolysis is essential for establishing pregnancy. Identifying the distinct features of early pregnancy CL remains unresolved, hence we analyzed here the transcriptome of CL on day 18 pregnant (P) and non-pregnant (NP) cows using RNA-Seq. CL of P cows expressed ISGs, verifying exposure to the pregnancy recognition signal, interferon-tau (IFNT), whereas the CL of NP cows had elevated luteal progesterone levels, implying that luteolysis had not yet commenced. Results The DEGs, IPA, and metascape canonical pathways, along with GSEA analysis, differed markedly in the CL of P cows from those of NP cows, at the same day of the cycle. Both metascape and IPA identified similar significantly enriched pathways such as interferon alpha/beta, sonic hedgehog pathway, TNFA, EDN1, TGFB1, and PDGF. However, type-1 interferon and sonic hedgehog pathways were positively enriched whereas most of the enriched pathways were downregulated in the P compared to NP samples. Thirty-four % of these pathways are known to be elevated by PGF2A during luteolysis. Notably, selective DEGs in luteinized granulosa cells were modulated by IFNT in vitro in a similar manner to their regulation in the CL of P cows. Conclusion This study unraveled the unique transcriptomic signature of the IFNT-exposed, early pregnancy CL, highlighting the abundance of downregulated pathways known to be otherwise induced during luteolysis. These and IFNT-regulated in vitro pregnancy-specific DEGs suggest that IFNT contributes to the characteristics and maintenance of early pregnancy CL.

Microarray reveals positive effects of green and black tea polyphenols on TNF[alpha]-induced changes of gene expression

2013 ◽  
Author(s):  
Husna Zulkipli ◽  
Norita Salim ◽  
Gabriele Anisah Froemming ◽  
Aletza Mohd Ismail ◽  
Hapizah Nawawi
Keyword(s):  
Gene Expression ◽  
Black Tea ◽  
Tea Polyphenols ◽  
Tnf Alpha ◽  
Positive Effects ◽  
Black Tea Polyphenols ◽  
Green And Black Tea ◽  
Induced Changes
Sign in / Sign up

Export Citation Format

Share Document