Possible role of interferon tau on the bovine corpus luteum and neutrophils during the early pregnancy

When pregnancy is established, interferon tau (IFNT), a well-known pregnancy recognition signal in ruminants, is secreted by embryonic trophoblast cells and acts within the uterus to prepare for pregnancy. IFNT acts as an endocrine factor on the corpus luteum (CL) to induce refractory ability against the luteolytic action of PGF2α. Hypothesising that IFNT may influence not only the uterine environment but also the CL in cows via local or peripheral circulation, we investigated qualitative changes in the CL of pregnant cows during the maternal recognition period (day 16) and the CL of non-pregnant cows. The CL of pregnant animals had a higher number of neutrophils, and the expression of interleukin 8 (IL8) mRNA and its protein was higher as well as compared with the CL of non-pregnant animals. Although IFNT did not affect progesterone (P4) secretion and neutrophil migration directly, it stimulated IL8 mRNA expression on luteal cells (LCs), influencing the neutrophils, resulting in the increased migration of IFNT-activated neutrophils. Moreover, both IFNT-activated neutrophils and IL8 increased P4 secretion from LCs in vitro. Our novel finding was the increase in neutrophils and IL8 within the CL of pregnant cows, suggesting the involvement of IFNT function within the CL toward establishment of pregnancy in cows. The present results suggest that IFNT upregulates neutrophil numbers and function via IL8 on LCs in the CL of early pregnant cows and that both neutrophils and IL8, stimulated by IFNT, are associated with an increase in P4 concentrations during the maternal recognition period in cows.

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

BMC Genomics ◽

10.1186/s12864-021-07747-3 ◽

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.

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Lipopolysaccharide enhances apoptosis of corpus luteum in isolated perfused bovine ovaries in vitro

Reproduction ◽

10.1530/rep-15-0281 ◽

2016 ◽

Vol 151 (1) ◽

pp. 17-28 ◽

Cited By ~ 7

Author(s):

J Lüttgenau ◽

B Möller ◽

D Kradolfer ◽

O Wellnitz ◽

R M Bruckmaier ◽

...

Keyword(s):

Corpus Luteum ◽

Structure And Function ◽

Prostaglandin Synthesis ◽

Gram Negative Bacteria ◽

Lps Challenge ◽

Bovine Corpus Luteum ◽

And Function ◽

Lps Treatment

Lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria, has detrimental effects on the structure and function of bovine corpus luteum (CL)in vivo. The objective was to investigate whether these effects were mediated directly by LPS orviaLPS-induced release of PGF2α. Bovine ovaries with a mid-cycle CL were collected immediately after slaughter and isolated perfused for 240 min. After 60 min of equilibration, LPS (0.5 μg/ml) was added to the medium of five ovaries, whereas an additional six ovaries were not treated with LPS (control). After 210 min of perfusion, all ovaries were treated with 500 iu of hCG. In the effluent perfusate, concentrations of progesterone (P4) and PGF2αwere measured every 10 and 30 min, respectively. Punch biopsies of the CL were collected every 60 min and used for RT-qPCR to evaluate mRNA expression of receptors for LPS (TLR2,-4) and LH (LHCGR); the cytokineTNFA; steroidogenic (STAR,HSD3B), angiogenic (VEGFA121,FGF2), and vasoactive (EDN1) factors; and factors of prostaglandin synthesis (PGES,PGFS,PTGFR) and apoptosis (CASP3,-8,-9). Treatment with LPS abolished the hCG-induced increase in P4(P≤0.05); however, there was a tendency (P=0.10) for increased release of PGF2αat 70 min after LPS challenge. Furthermore, mRNA abundance ofTLR2,TNFA,CASP3,CASP8,PGES,PGFS, andVEGFA121increased (P≤0.05) after LPS treatment, whereas all other factors remained unchanged (P>0.05). In conclusion, reduced P4responsiveness to hCG in LPS-treated ovariesin vitrowas not due to reduced steroidogenesis, but was attributed to enhanced apoptosis. However, an impact of luteal PGF2αcould not be excluded.

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Biosynthesis of Progesterone, Sterols, and Squalene from Acetate-1-14C and Mevalonate-2-14C by the Bovine Corpus Luteum in Vitro

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)97410-7 ◽

1965 ◽

Vol 240 (5) ◽

pp. 1957-1961

Author(s):

Hermione R. Hellig ◽

Kenneth Savard

Keyword(s):

Corpus Luteum ◽

Bovine Corpus Luteum

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In Vitro Production of Angiotropic Factor by Bovine Corpus Luteum: Partial Characterization of Activities that are Chemotactic and Mitogenic for Endometrial Cells

Advances in Experimental Medicine and Biology - Regulation of Ovarian and Testicular Function ◽

10.1007/978-1-4684-5395-9_42 ◽

1987 ◽

pp. 683-688 ◽

Cited By ~ 8

Author(s):

D. A. Redmer ◽

J. D. Kirsch ◽

A. T. Grazul

Keyword(s):

Corpus Luteum ◽

Partial Characterization ◽

In Vitro Production ◽

Endometrial Cells ◽

Bovine Corpus Luteum ◽

Vitro Production

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Control of Steroidogenesis in Small and Large Bovine Luteal. Cells

Australian Journal of Biological Sciences ◽

10.1071/bi9870331 ◽

1987 ◽

Vol 40 (3) ◽

pp. 331 ◽

Cited By ~ 45

Author(s):

William Hansel ◽

Hector W Alila ◽

Joseph P Dowd ◽

Xiangzhong Yang

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Corpus Luteum ◽

Luteal Cell ◽

Lipoxygenase Pathway ◽

Luteal Cells ◽

Kinase C ◽

Bovine Corpus Luteum ◽

Progesterone Synthesis

Evidence was cited to show that: (1) prostacyclin (PGI2) plays a luteotrophic role in the bovine corpus luteum and that products of the lipoxygenase pathway of arachidonic acid metabolism, especially 5-hydroxyeicosatetraenoic acid play luteolytic roles; (2) oxytocin of luteal cell origin plays a role in development, and possibly in regression, of the bovine corpus luteum; and (3) luteal cells arise from two sources; the characteristic small luteal cells at all stages of the o~strous cycle and pregnancy are of theca cell origin; the large cells are of granulosa cell origin early in the cycle, but a population of theca-derived large cells appears later in the cycle. Results of in vitro studies with total dispersed cells and essentially pure preparations of large and small luteal cells indicate that : (1) the recently described Ca2+ -polyphosphoinositol-protein kinase C second messenger system is involved in progesterone synthesis in the bovine corpus luteum; (2) activation of protein kinase C is stimulatory to progesterone synthesis in the small luteal cells; (3) activation of protein kinase C has no effect on progesterone synthesis in the large luteal cells; and (4) protein kinase C exerts its luteotrophic effect in total cell preparations, in part at least, by stimulating the production of prostacyclin. The protein kinase C system may cause down regulation of LH receptors in the large cells.

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

Reproduction Fertility and Development ◽

10.1071/rdv25n1ab109 ◽

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).

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Expression of CA-125 by progestational bovine endometrium: prospective regulation and function

Reproduction ◽

10.1530/rep.0.1260615 ◽

2003 ◽

pp. 615-620 ◽

Cited By ~ 11

Author(s):

AC McDonnel ◽

EA Van Kirk ◽

KJ Austin ◽

TR Hansen ◽

EL Belden ◽

...

Keyword(s):

Epithelial Cells ◽

Ovarian Cancer Cell Line ◽

Amino Acid Content ◽

Ca 125 ◽

Embryonic Cells ◽

Cancer Antigen 125 ◽

Interferon Tau ◽

Endometrial Cells ◽

And Function

Cancer antigen 125 (CA-125) is expressed by malignant human ovarian surface epithelial cells and derivatives of the Mullerian duct system. This study explored the expression, regulation, and function of CA-125 in the bovine uterus. CA-125 was localized by immunohistochemistry to the apical surfaces of epithelial cells lining the endometrium and proximal glands of the late luteal phase and early pregnancy; antigen was not detected during oestrus or the postpartum period. Production of CA-125 by bovine endometrial cells in vitro was upregulated by progesterone and interferon-tau. Immunopurified CA-125 from uterine flushes of dioestrous or pregnant cows was similar in biochemical composition (as determined by gel electrophoresis and amino acid content) to the human antigen isolated from incubation medium conditioned by the ovarian cancer cell line OVCAR-3. Bovine CA-125 inhibited complement-induced lysis of antibody-sensitized sheep erythrocytes. It is suggested that endometrial CA-125 exerts a progestational role in part by protecting maternal and embryonic cells from immune targeting and lysis.

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Does prostacyclin (PGI2) support porcine corpus luteum function? – data from in vitro study

Problems of Endocrinology ◽

10.14341/probl201662549 ◽

2016 ◽

Vol 62 (5) ◽

pp. 49

Author(s):

Magdalena Julia Szymańska ◽

Agnieszka Blitek

Keyword(s):

Endothelial Cells ◽

Mrna Expression ◽

Corpus Luteum ◽

Estrous Cycle ◽

In Vitro Study ◽

Luteal Cells ◽

Enzymatic Isolation ◽

Effective Doses ◽

And Function

Background. Prostacyclin (PGI2) of luteal origin is involved in the control of corpus luteum (CL) development and function in cattle. PGI2 may regulate the process of angiogenesis and may stimulate progesterone (P4) secretion by luteal cells via its specific receptors, PTGIR. In contrast to cattle, the role of PGI2 in the pig CL has not yet been described.Aim. The present study aimed to investigate the effect of PGI2 on 1) P4 secretion by luteal cells, and 2) the expression of angiogenesis-related genes in endothelial cells of the porcine CL.Methods. CL collected from gilts on day 5-7 of the estrous cycle were used for enzymatic isolation of luteal (Experiment 1) and endothelial (Experiment 2) cells. In Exp. 1, cultured luteal cells were incubated with increasing (0, 0.01, 0.1, 1, 5 µM) doses of PGI2 analogues: iloprost (ILO) and carbaprostacyclin (cPGI2) for 8 h. To determine the effective doses of PGI2 analogues, P4 concentration in culture medium was examined by RIA. Thereafter, luteal cells were treated with ILO and cPGI2 at the concentration of 1 and 5 µM in the presence or absence of PTGIR antagonist (CAY10441). After 8 h of incubation the medium was collected for P4 determination. In Exp. 2, isolated endothelial cells were treated for 24 h with ILO and cPGI2 at doses of 1 and 5 µM. Then, cells were collected for analysis of Ang-1 and -2 mRNA expression using qPCR.Results. Both, ILO and cPGI2 affected P4 secretion by luteal cells. Elevated levels of P4 were observed in medium after treatment of luteal cells with 1 µM of ILO and 0.1, 1 and 5 µM of cPGI2 compared with control values (p<0.05). The addition of CAY10441 inhibited the stimulatory effect of ILO on P4 secretion, while did not change P4 production by luteal cells incubated with cPGI2. Moreover, PGI2 analogues differentially affected (p<0.05) the expression of proangiogenic factors. ILO stimulated Ang-2, whereas cPGI2 positively affected Ang-1 mRNA expression in endothelial cells at concentrations of 1 µM and 5 µM, respectively.Conclusion. PGI2 affects P4 secretion during luteal phase of the estrous cycle and may regulate the process of angiogenesis in the porcine CL.

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