scholarly journals Progesterone and interferon tau-regulated genes in the ovine uterine endometrium: identification of periostin as a potential mediator of conceptus elongation

Reproduction ◽  
2009 ◽  
Vol 138 (5) ◽  
pp. 813-825 ◽  
Author(s):  
Hyo Won Ahn ◽  
Jennifer L Farmer ◽  
Fuller W Bazer ◽  
Thomas E Spencer
Keyword(s):  
Early Pregnancy ◽  
Calcium Binding ◽  
Collagen Type ◽  
Cdna Array ◽  
Interferon Tau ◽  
Uterine Endometrium ◽  
S100 Calcium Binding Protein ◽  
Trophectoderm Cells ◽  
Conceptus Development

During early pregnancy in ruminants, progesterone (P4) and interferon tau (IFNT) act on the endometrium to regulate genes hypothesized to be important for conceptus development and implantation. The present study was conducted to verify several candidate genes (actin α-2, smooth muscle, aorta (ACTA2), collagen, type III, α-1 (COL3A1), periostin (POSTN), secreted protein acidic cysteine-rich (SPARC), S100 calcium-binding protein A2 (S100A2),STAT5Aand transgelin (TAGLN)) regulated by pregnancy, P4, and/or IFNT in the endometrium determined using a custom ovine cDNA array.S100A2mRNA was detected primarily in endometrial epithelia and conceptuses.S100A2mRNA increased in endometrial epithelia from days 10 to 16 in cyclic ewes and from days 10 to 14 in pregnant ewes and declined thereafter. The abundance ofS100A2mRNA was less in endometrial luminal epithelium of IFNT-infused ewes receiving P4. Expression ofCOL3A1, SPARC, ACTA2, andTAGLNwas independent of pregnancy, P4, or IFNT.POSTNmRNA was detected primarily in compact stroma of intercaruncular and caruncular endometria, but not in the conceptus. EndometrialPOSTNmRNA increased between days 12 and 14 in pregnant but not cyclic ewes, andPOSTNmRNA was more abundant in uterine stroma of ewes treated with P4. POSTN protein was detected in uterine flushings of pregnant ewes and found to mediate attachment and stimulate migration of ovine trophectoderm cellsin vitro. These results support the ideas that POSTN and S100A2 are regulated by P4and IFNT respectively, and that POSTN is involved in conceptus elongation during early pregnancy.

scholarly journals Several fibroblast growth factors are expressed during pre-attachment bovine conceptus development and regulate interferon-tau expression from trophectoderm

Reproduction ◽  
2009 ◽  
Vol 137 (2) ◽  
pp. 259-269 ◽  
Author(s):  
Flavia N T Cooke ◽  
Kathleen A Pennington ◽  
Qien Yang ◽  
Alan D Ealy
Keyword(s):  
Growth Factors ◽  
Fibroblast Growth Factors ◽  
Mrna Levels ◽  
Fibroblast Growth ◽  
Blastocyst Development ◽  
Interferon Tau ◽  
Trophectoderm Cells ◽  
Conceptus Development

The trophectoderm-derived factor interferon tau (IFNT) maintains the uterus in a pregnancy-receptive state in cattle and sheep. Fibroblast growth factors (FGFs) are implicated in regulatingIFNTexpression and potentially other critical events associated with early conceptus development in cattle. The overall objectives of this work were to identify the variousFGFsand FGF receptors (FGFRs) expressed in elongating pre-attachment bovine conceptuses and determine if these FGFs regulate conceptus development and/or mediate IFNT production.In vitro-derived bovine blastocysts andin vivo-derived elongated conceptuses collected at day 17 of pregnancy express at least fourFGFRsubtypes (R1c,R2b,R3c,R4). In addition, transcripts forFGF1,2, and10but notFGF7are present in elongated bovine conceptuses. The expression pattern ofFGF10most closely resembled that ofIFNT, with both transcripts remaining low in day 8 and day 11 conceptuses and increasing substantially in day 14 and day 17 conceptuses. Supplementation with recombinant FGF1, 2 or 10 increasedIFNTmRNA levels in bovine trophectoderm cells and bovine blastocysts and increased IFNT protein concentrations in trophectoderm-conditioned medium. Blastocyst development was not affected by any of the FGFs. In summary, at least four FGFRs reside in pre- and peri-attachment bovine conceptuses. Moreover, conceptuses express at least three candidate FGFs during elongation, the time of peakIFNTexpression. These findings provide new insight for how conceptus-derived factors such as FGF1, 2, and 10 may controlIFNTexpression during early pregnancy in cattle.

scholarly journals The effect of pregnancy on the expression of uterine oxytocin, oestrogen and progesterone receptors during early pregnancy in the cow

1999 ◽  
Vol 160 (1) ◽  
pp. 21-33 ◽  
Author(s):  
RS Robinson ◽  
GE Mann ◽  
GE Lamming ◽  
DC Wathes
Keyword(s):  
Cross Sections ◽  
Early Pregnancy ◽  
In Situ Hybridisation ◽  
Progesterone Receptors ◽  
Prostaglandin F2alpha ◽  
Interferon Tau ◽  
Uterine Endometrium ◽  
Low Concentrations ◽  
Oxytocin Antagonist

The expression of oxytocin receptor (OTR) in the uterine endometrium plays an important role in the initiation of luteolysis. During early pregnancy, the conceptus secretes interferon tau (IFN|gt) which inhibits OTR up-regulation and luteolysis. In this study, uterine horn cross sections were collected on day 16 from 15 pregnant cows (PREG), 9 uninseminated controls and 5 inseminated cows with no embryo present. The latter two groups had similar results and were combined to form a single non-pregnant (NP) group. The animals were given an oxytocin challenge shortly before tissue collection to assess prostaglandin F2alpha (PGF2alpha) release through the measurement of the metabolite 13,14-dihydro-15-keto PGF2alpha (PGFM). The mRNAs for OTR, oestrogen receptor (ER) and progesterone receptor (PR) were localised by in situ hybridisation. The results were quantified by optical density (OD) measurements from autoradiographs using image analysis. OTR protein was measured by autoradiography with iodinated oxytocin antagonist and ER and PR protein was detected by immunocytochemistry. The release of PGFM after the oxytocin challenge was significantly higher in the 14 NP cows (187%+/-15%) compared with the PREG group (131%+/-11%) (P<0.01). Low concentrations of OTR mRNA were localised to the luminal epithelium (LE) in 6 out of the 14 NP cows, of which 2 also expressed OTR protein, while OTR mRNA and protein were undetectable in all the pregnant animals. These results indicated that the sampling time coincided with the onset of the luteolytic mechanism in the NP cows. On day 16 ER mRNA was detectable in both the LE and glands of both PREG and NP animals. There were no differences in either ER mRNA or protein between NP and PREG samples. PR mRNA was moderately expressed in the caruncular stroma, with lower levels in the dense caruncular-like stroma and glands. There were no differences between PREG and NP animals. The expression of PR mRNA and protein in the deep glands was variable between animals. These results suggested that, in cows, the presence of an embryo suppressed the expression of OTR, but had no effect on the expression of the transcriptionally regulated ER on day 16.

109 EFFECT OF SHORT TERM PROGESTERONE SUPPLEMENTATION ON CIRCULATING PROGESTERONE CONCENTRATION, CORPUS LUTEUM SIZE, AND EARLY EMBRYO DEVELOPMENT IN CATTLE

2013 ◽  
Vol 25 (1) ◽  
pp. 202
Author(s):  
L. O'Hara ◽  
N. Forde ◽  
D. Rizos ◽  
V. Maillo ◽  
A. D. Ealy ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Early Embryo ◽  
Negative Effects ◽  
Short Term ◽  
Concentration Data ◽  
Interferon Tau ◽  
Fluid Medium ◽  
Conceptus Development ◽  
Oviduct Fluid

The aim of this study was to investigate the effect of short term progesterone (P4) supplementation on circulating P4 concentrations, corpus luteum (CL) size, and conceptus development in cattle. The oestrous cycles of crossbred beef heifers were synchronised using a 7-day PRID® Delta (1.55 g P4) treatment with administration of a PGF2α analog (Enzaprost®) the day before PRID® Delta removal. Only those recorded in standing oestrus (Day 0) were used. In Experiment 1, heifers were randomly assigned to 1 of 5 groups: (1) control: no treatment, (2) placebo: insertion of a blank device (no P4) from Day 3 to 7, (3) insertion of a PRID® Delta from Day 3 to 7, (4) insertion of a PRID® Delta from Day 3 to 5, or (v5) insertion of a PRID® Delta from Day 5 to 7. In vitro produced blastocysts were transferred to each heifer on Day 7 (10 blastocysts per heifer) and conceptuses were recovered at slaughter on Day 14. In Experiment 2 heifers were artificially inseminated at oestrus and randomly assigned to 1 of 3 treatment groups (1) placebo, (2) PRID® Delta from Day 3 to 5, or (3) PRID® Delta from Day 3 to 7. All heifers were slaughtered on Day 16, and recovered conceptuses were incubated in synthetic oviduct fluid medium for 24 h; spent media and uterine flushes were analysed for interferon-tau (IFNT). In both experiments, daily blood samples were taken to measure serum P4 concentration. Data were analysed using the PROC MIXED procedure of SAS (SAS Institute Inc., Cary, NC, USA). Insertion of a PRID® Delta resulted in an increase (P < 0.05) in serum P4, which declined following removal. In Experiment 1, serum P4 concentration was significantly lower from Day 9 to 14 (P < 0.05) and Day 14 CL weight was lower in the PRID® Delta Day 3 to 7 group than the placebo or control groups. P4 supplementation from Day 3 to 5 (17.0 ± 1.4 mm) or Day 3 to 7 (11.3 ± 2.3 mm) increased conceptus length compared to the placebo (2.1 ± 1.8 mm). In Experiment 2, serum P4 was significantly lower in the two supplemented groups following PRID® Delta removal compared with the placebo (P < 0.05) and was associated with a lower CL weight in the Day 3 to 7 group. Supplementation from Day 3 to 5 (94.0 ± 18.8 mm) or Day 3 to 7 (143.6 ± 20.6 mm) increased conceptus length on Day 16 compared to the placebo (50.3 ± 17.4 mm). Conceptus length was strongly correlated with the concentration of IFNT in the uterine flush (r = 0.58; P = 0.011) and spent culture medium (r = 0.68; P < 0.002). These findings highlight the somewhat paradoxical effects of P4 supplementation when given in the early metoestrus period in terms of its positive effect on conceptus development and its potentially negative effects on CL lifespan. Supported by CEVA Sante Animale and Science Foundation Ireland (07/SRC/B1156).

scholarly journals Cortisol and Interferon Tau Regulation of Endometrial Function and Conceptus Development in Female Sheep

Endocrinology ◽  
2012 ◽  
Vol 154 (2) ◽  
pp. 931-941 ◽  
Author(s):  
Piotr Dorniak ◽  
Thomas H. Welsh ◽  
Fuller W. Bazer ◽  
Thomas E. Spencer
Keyword(s):  
Early Pregnancy ◽  
Reductase Activity ◽  
In Utero ◽  
Selective Inhibitor ◽  
Biological Role ◽  
Interferon Tau ◽  
Uterine Lumen ◽  
Conceptus Development ◽  
Female Sheep ◽  
Expression And Activity

During early pregnancy in sheep, the elongating conceptus secretes interferon-τ (IFNT) and the conceptus as well as endometrial epithelia produce prostaglandins (PG) via PG synthase 2 (PTGS2) and cortisol via hydroxysteroid (11-β) dehydrogenase 1 (HSD11B1). Ovarian progesterone induces and PG and IFNT stimulates endometrial HSD11B1 expression and keto-reductase activity as well as many epithelial genes that govern trophectoderm proliferation, migration, and attachment during elongation. The primary aim of these studies was to test the hypothesis that HSD11B1-derived cortisol has a biological role in endometrial function and conceptus development during early pregnancy in sheep. In study 1, cyclic ewes received vehicle, cortisol, PF 915275 (PF; a selective inhibitor of HSD11B1), cortisol and PF, meloxicam (a selective inhibitor of PTGS2), cortisol and meloxicam, recombinant ovine IFNT, or IFNT and PF into the uterus from day 10 to day14 after estrus. Cortisol and IFNT stimulated endometrial HSD11B1 expression and activity, increased endometrial PTGS2 activity and the amount of PG in the uterine lumen, and up-regulated many conceptus elongation-related genes in the endometrium. Some effects of cortisol and IFNT were mediated by PTGS2-derived PG. In study 2, bred ewes received PF 915275 or recombinant ovine IFNT and into the uterus from day 10 to day 14 after mating. Inhibition of HSD11B1 activity in utero prevented conceptus elongation, whereas IFNT rescued conceptus elongation in PF-infused ewes. These results suggest that HSD11B1-derived cortisol mediates, in part, actions of ovarian progesterone and the conceptus on endometrial function and support the hypothesis that IFNT, PG, and cortisol coordinately regulate endometrial functions important for conceptus elongation and implantation during early pregnancy in sheep.

scholarly journals Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow

Reproduction ◽  
2011 ◽  
Vol 142 (6) ◽  
pp. 879-892 ◽  
Author(s):  
Akane Nitta ◽  
Koumei Shirasuna ◽  
Shingo Haneda ◽  
Motozumi Matsui ◽  
Takashi Shimizu ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Corpus Luteum ◽  
Early Pregnancy ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cell ◽  
Circulation System ◽  
Interferon Tau ◽  
Factor C

The corpus luteum (CL), which secretes large amounts of progesterone and is thus essential for establishing pregnancy, contains various types of immune cells that may play essential roles in CL function by generating immune responses. The lymphatic system is the second circulation system and is necessary for immune function, but the lymphatic system of the bovine CL has not been characterized in detail. We collected bovine CLs on days 12 and 16 of the estrous cycle (C12 and C16) and days 16 and 40 of early pregnancy (P16 and P40). Lymphatic endothelial hyaluronan receptor 1 (LYVE1) protein was detected in the CL by immunohistochemistry and western blotting and increased at P40 compared with C16. The mRNA expression levels of lymphangiogenic factors, such as vascular endothelial growth factor-C (VEGFC),VEGFD, and their common receptorVEGFR3, as well as the lymphatic endothelial cell (LyEC) marker podoplanin, increased in P16 and P40 CLs. Thus, it is suggested that the lymphatic system of the bovine CL reconstitutes during early pregnancy. Interferon tau (IFNT) from the conceptus in the uterus is a candidate for activating luteal lymphangiogenesis during the maternal recognition period (MRP). We found that treatment of LyECs isolated from internal iliac lymphatic vessels with IFNT stimulated LyEC proliferation and significantly increased mRNA expression ofVEGFCand IFN-stimulated gene 15. Moreover, both IFNT and VEGFC induced LyECs to form capillary-like tubesin vitro. In conclusion, it is suggested that new lymphangiogenesis in the bovine CL begins during the MRP and that IFNT may mediate this novel phenomenon.

Role of progesterone in embryo development in cattle

2016 ◽  
Vol 28 (2) ◽  
pp. 66 ◽  
Author(s):  
Pat Lonergan ◽  
Niamh Forde ◽  
Thomas Spencer
Keyword(s):  
Corpus Luteum ◽  
Embryo Development ◽  
Early Pregnancy ◽  
Pregnancy Rates ◽  
In Vitro Experiments ◽  
Conceptus Development

Progesterone (P4) from the corpus luteum is critical for the establishment and maintenance of pregnancy and plays a major role in regulating endometrial secretions essential for stimulating and mediating changes in conceptus growth and differentiation throughout early pregnancy in ruminants. Numerous studies have demonstrated an association between elevated systemic P4 and acceleration in conceptus elongation. A combination of in vivo and in vitro experiments found that the effects of P4 on conceptus elongation are indirect and mediated through P4-induced effects in the endometrium. Despite effects on elongation, data on the effects of post-insemination supplementation with P4 on pregnancy rates are conflicting. This review highlights the effects of P4 on conceptus development and examines strategies that have been undertaken to manipulate P4 concentrations to increase fertility.

scholarly journals Feeder Cell Type Affects the Growth of In Vitro Cultured Bovine Trophoblast Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Islam M. Saadeldin ◽  
Ahmed Abdelfattah-Hassan ◽  
Ayman Abdel-Aziz Swelum
Keyword(s):  
Granulosa Cells ◽  
Current Approach ◽  
Embryonic Cells ◽  
Interferon Tau ◽  
Porcine Granulosa Cells ◽  
Trophectoderm Cells ◽  
Homeobox Protein ◽  
First Time

Trophectoderm cells are the foremost embryonic cells to differentiate with prospective stem-cell properties. In the current study, we aimed at improving the current approach for trophoblast culture by using granulosa cells as feeders. Porcine granulosa cells (PGCs) compared to the conventional mouse embryonic fibroblasts (MEFs) were used to grow trophectoderm cells from hatched bovine blastocysts. Isolated trophectoderm cells were monitored and displayed characteristic epithelial/cuboidal morphology. The isolated trophectoderm cells expressed mRNA of homeobox protein (CDX2), cytokeratin-8 (KRT8), and interferon tau (IFNT). The expression level was higher on PGCs compared to MEFs throughout the study. In addition, primary trophectoderm cell colonies grew faster on PGCs, with a doubling time of approximately 48 hrs, compared to MEFs. PGCs feeders produced a fair amount of 17β-estradiol and progesterone. We speculated that the supplementation of sex steroids and still-unknown factors during the trophoblasts coculture on PGCs have helped to have better trophectoderm cell’s growth than on MEFs. This is the first time to use PGCs as feeders to culture trophectoderm cells and it proved superior to MEFs. We propose PGCs as alternative feeders for long-term culture of bovine trophectoderm cells. This model will potentially benefit studies on the early trophoblast and embryonic development in bovines.

scholarly journals Interferon-Tau Exerts Direct Prosurvival and Antiapoptotic Actions in Luteinized Bovine Granulosa Cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Raghavendra Basavaraja ◽  
Senasige Thilina Madusanka ◽  
Jessica N. Drum ◽  
Ketan Shrestha ◽  
Svetlana Farberov ◽  
...  
Keyword(s):  
Cell Viability ◽  
Granulosa Cells ◽  
Early Pregnancy ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Interferon Tau ◽  
Cell Counts ◽  
Domestic Ruminants ◽  
Stat1 Protein

Abstract Interferon-tau (IFNT), serves as a signal to maintain the corpus luteum (CL) during early pregnancy in domestic ruminants. We investigated here whether IFNT directly affects the function of luteinized bovine granulosa cells (LGCs), a model for large-luteal cells. Recombinant ovine IFNT (roIFNT) induced the IFN-stimulated genes (ISGs; MX2, ISG15, and OAS1Y). IFNT induced a rapid and transient (15–45 min) phosphorylation of STAT1, while total STAT1 protein was higher only after 24 h. IFNT treatment elevated viable LGCs numbers and decreased dead/apoptotic cell counts. Consistent with these effects on cell viability, IFNT upregulated cell survival proteins (MCL1, BCL-xL, and XIAP) and reduced the levels of gamma-H2AX, cleaved caspase-3, and thrombospondin-2 (THBS2) implicated in apoptosis. Notably, IFNT reversed the actions of THBS1 on cell viability, XIAP, and cleaved caspase-3. Furthermore, roIFNT stimulated proangiogenic genes, including FGF2, PDGFB, and PDGFAR. Corroborating the in vitro observations, CL collected from day 18 pregnant cows comprised higher ISGs together with elevated FGF2, PDGFB, and XIAP, compared with CL derived from day 18 cyclic cows. This study reveals that IFNT activates diverse pathways in LGCs, promoting survival and blood vessel stabilization while suppressing cell death signals. These mechanisms might contribute to CL maintenance during early pregnancy.

scholarly journals Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

Reproduction ◽  
2015 ◽  
Vol 149 (4) ◽  
pp. 305-316 ◽  
Author(s):  
Irene Ruiz-González ◽  
Megan Minten ◽  
Xiaoqiu Wang ◽  
Kathrin A Dunlap ◽  
Fuller W Bazer
Keyword(s):  
Estrous Cycle ◽  
Antisense Oligonucleotides ◽  
Endogenous Retrovirus ◽  
Innate Immune ◽  
Reproductive Status ◽  
Loss Of Function ◽  
Interferon Tau ◽  
Trophectoderm Cells ◽  
Conceptus Development

Toll-like receptors (TLRs) belong to the innate immune system and regulate inflammatory events that affect mammalian reproduction. In Study 1, we demonstrated that abundance of ovine TLR1–TLR9 mRNAs in the uterus differs due to reproductive status (TLR2, TLR3, TLR7, and TLR8) and the day of the estrous cycle and pregnancy (TLR1–TLR3, TLR5–TLR7, and TLR9). Expression of TLR7 and TLR8 proteins was localized primarily to uterine epithelia and stroma and regulated in a temporal manner. In Study 2, we determined that ovine conceptuses express TLR7 and TLR8 on all days studied and that expression of the envelope protein of ovine endogenous retrovirus (enJSRV-Env) declined in conceptus trophectoderm from Day 13 to Day 16 of pregnancy. In Study 3, loss-of-function experiments were conducted in vivo using morpholino antisense oligonucleotides (MAOs) injected into the uterine lumen to block synthesis of TLR7 and TLR8 proteins, individually and jointly. Conceptuses were recovered on Day 16 to assess their morphology. MAO-treated conceptuses were developmentally retarded, produced less interferon tau (IFNT), and had fewer binucleate cells (BNCs) compared with MAO-Controls. Moreover, expression of enJSRV-Env mRNA in MAO-TLR7 conceptuses was greater than that for MAO-Control and MAO-TLR8 conceptuses, but similar to MAO-TLR7/TLR8 conceptuses. Results of this study indicated differences in TLR1–TLR9 expression due to reproductive status and the day of the estrous cycle and pregnancy. TLR7 and TLR8 also influence development, enJSRV-Env abundance, secretion of IFNT, and formation of BNCs by conceptuses. These findings corroborate our hypothesis that TLR7 and TLR8 mediate pathways whereby enJSRV-Env regulates key peri-implantation events in conceptus development and differentiated functions of trophectoderm cells.

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