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Article ; Online: Dose- and time-dependent effects of interferon tau on bovine endometrial gene expression

Talukder, A.K. / Rabaglino, M.B. / Browne, J.A. / Charpigny, G. / Lonergan, P.

Theriogenology. 2023 Nov., v. 211 p.1-10

2023

Abstract: Failure by the developing conceptus to secrete sufficient interferon tau (IFNT), required for maternal recognition of pregnancy (MRP), at the appropriate time is related to early pregnancy loss in cattle. We aimed to test the hypothesis that there is a ... ...

Abstract	Failure by the developing conceptus to secrete sufficient interferon tau (IFNT), required for maternal recognition of pregnancy (MRP), at the appropriate time is related to early pregnancy loss in cattle. We aimed to test the hypothesis that there is a dose- and time-dependent relationship between IFNT and the endometrial expression of key interferon-stimulated genes (ISGs) involved in the signalling cascade leading to MRP in cattle. Candidate genes were identified first through a bioinformatic approach, where integrated transcriptomic data from two previous studies were analyzed to identify endometrial genes induced by IFNT. Next, expression of selected candidate genes was investigated in vitro in endometrial explants. Endometrial explants collected from cows (n = 8) in the late luteal phase of the estrous cycle were cultured in medium without (control) or with recombinant ovine IFNT (1, 10, 100 ng/mL) for 6 h. Simultaneously, endometrial explants were cultured in medium containing 100 ng/mL IFNT for different time periods (15 min, 30 min, 1 h, 3 h, 6 h). Gene expression was analyzed by RT-qPCR. We identified 54 endometrial genes responding to IFNT and to some degree to the conceptus, from which five ISGs (CMPK2, BPNT1, IFI35, TNFSF10 and TRIM38) were further selected for the dose- and time-dependent experiments. Classical ISGs (ISG15, OAS1, MX1 and MX2) were up-regulated (P < 0.05) in endometrium by 1 ng/mL IFNT. However, other selected ISGs (CMPK2, BPNT1, IFI35, TNFSF10 and TRIM38) were induced only by higher concentrations (10 and 100 ng/mL) of IFNT (P < 0.05). In terms of duration of exposure, IFNT at 100 ng/mL induced a significant (P < 0.05) increase in ISG15 and CMPK2 expression after 1 h incubation, while all other studied ISGs in the endometrium were upregulated when cultured for 3 or 6 h, but did not affect expression when the duration of culture was for 1 h or less. These results suggest that IFNT acts on the uterus in both a dose- and time-dependent manner in cattle and that timely exposure of the endometrium to sufficient IFNT is essential for appropriate signalling to ensure successful pregnancy establishment.
Keywords	bioinformatics ; cattle ; conceptus ; endometrium ; estrous cycle ; gene expression ; interferons ; menstrual cycle ; pregnancy ; sheep ; transcriptomics ; Explant ; Interferon tau ; Bovine
Language	English
Dates of publication	2023-11
Size	p. 1-10.
Publishing place	Elsevier Inc.
Document type	Article ; Online
ZDB-ID	189232-0
ISSN	1879-3231 ; 0093-691X
ISSN (online)	1879-3231
ISSN	0093-691X
DOI	10.1016/j.theriogenology.2023.07.033
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Article ; Online: Dose- and time-dependent effects of interferon tau on bovine endometrial gene expression.

Talukder, A K / Rabaglino, M B / Browne, J A / Charpigny, G / Lonergan, P

Theriogenology

2023 Volume 211, Page(s) 1–10

Abstract	Failure by the developing conceptus to secrete sufficient interferon tau (IFNT), required for maternal recognition of pregnancy (MRP), at the appropriate time is related to early pregnancy loss in cattle. We aimed to test the hypothesis that there is a dose- and time-dependent relationship between IFNT and the endometrial expression of key interferon-stimulated genes (ISGs) involved in the signalling cascade leading to MRP in cattle. Candidate genes were identified first through a bioinformatic approach, where integrated transcriptomic data from two previous studies were analyzed to identify endometrial genes induced by IFNT. Next, expression of selected candidate genes was investigated in vitro in endometrial explants. Endometrial explants collected from cows (n = 8) in the late luteal phase of the estrous cycle were cultured in medium without (control) or with recombinant ovine IFNT (1, 10, 100 ng/mL) for 6 h. Simultaneously, endometrial explants were cultured in medium containing 100 ng/mL IFNT for different time periods (15 min, 30 min, 1 h, 3 h, 6 h). Gene expression was analyzed by RT-qPCR. We identified 54 endometrial genes responding to IFNT and to some degree to the conceptus, from which five ISGs (CMPK2, BPNT1, IFI35, TNFSF10 and TRIM38) were further selected for the dose- and time-dependent experiments. Classical ISGs (ISG15, OAS1, MX1 and MX2) were up-regulated (P < 0.05) in endometrium by 1 ng/mL IFNT. However, other selected ISGs (CMPK2, BPNT1, IFI35, TNFSF10 and TRIM38) were induced only by higher concentrations (10 and 100 ng/mL) of IFNT (P < 0.05). In terms of duration of exposure, IFNT at 100 ng/mL induced a significant (P < 0.05) increase in ISG15 and CMPK2 expression after 1 h incubation, while all other studied ISGs in the endometrium were upregulated when cultured for 3 or 6 h, but did not affect expression when the duration of culture was for 1 h or less. These results suggest that IFNT acts on the uterus in both a dose- and time-dependent manner in cattle and that timely exposure of the endometrium to sufficient IFNT is essential for appropriate signalling to ensure successful pregnancy establishment.
MeSH term(s)	Pregnancy ; Female ; Cattle ; Animals ; Sheep ; Abortion, Veterinary ; Interferon Type I/genetics ; Interferon Type I/pharmacology ; Interferon Type I/metabolism ; Endometrium/metabolism ; Gene Expression ; Cattle Diseases/metabolism ; Sheep Diseases
Chemical Substances	interferon tau ; Interferon Type I
Language	English
Publishing date	2023-07-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	189232-0
ISSN	1879-3231 ; 0093-691X
ISSN (online)	1879-3231
ISSN	0093-691X
DOI	10.1016/j.theriogenology.2023.07.033
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Article ; Online: Mismatch repair mRNA and protein expression in intestinal adenocarcinoma in sika deer (Cervus nippon) resembling heritable non-polyposis colorectal cancer in man.

Jahns, H / Browne, J A

Journal of comparative pathology

2015 Volume 152, Issue 2-3, Page(s) 131–137

Abstract: Intestinal adenocarcinomas seen in an inbred herd of farmed sika deer (Cervus nippon) morphologically resembled human hereditary non-polyposis colorectal cancer (HNPCC). Features common to both included multiple de novo sites of tumourigenesis in the ... ...

Abstract	Intestinal adenocarcinomas seen in an inbred herd of farmed sika deer (Cervus nippon) morphologically resembled human hereditary non-polyposis colorectal cancer (HNPCC). Features common to both included multiple de novo sites of tumourigenesis in the proximal colon, sessile and non-polyposis mucosal changes, the frequent finding of mucinous type adenocarcinoma, lymphocyte infiltration into the neoplastic tubules and Crohn's-like lymphoid follicles at the deep margin of the tumour. HNPCC is defined by a germline mutation of mismatch repair (MMR) genes resulting in their inactivation and loss of expression. To test the hypothesis that similar MMR gene inactivation occurs in the deer tumours, the expression of the four most important MMR genes, MSH2, MLH1, MSH6 and PMS2, was examined at the mRNA level by reverse transcriptase polymerase chain reaction (n = 12) and at the protein level by immunohistochemistry (n = 40) in tumour and control tissues. All four genes were expressed equally in normal and neoplastic tissues, so MMR gene inactivation could not be implicated in the carcinogenesis of this tumour in sika deer.
MeSH term(s)	Adenocarcinoma/genetics ; Adenocarcinoma/veterinary ; Animals ; DNA Mismatch Repair/genetics ; Deer ; Humans ; Immunohistochemistry ; Intestinal Neoplasms/genetics ; Intestinal Neoplasms/veterinary ; RNA, Messenger/analysis ; RNA, Messenger/biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2015-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	390920-7
ISSN	1532-3129 ; 0021-9975
ISSN (online)	1532-3129
ISSN	0021-9975
DOI	10.1016/j.jcpa.2014.12.003
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Article ; Online: Transcriptional networks in the human epididymis.

Browne, J A / Leir, S-H / Yin, S / Harris, A

Andrology

2019 Volume 7, Issue 5, Page(s) 741–747

Abstract: Background: The epithelial lining of the human epididymis is critical for sperm maturation. This process requires distinct specialized functions in the head, body, and tail of the duct. These region-specific properties are maintained by distinct gene ... ...

Abstract	Background: The epithelial lining of the human epididymis is critical for sperm maturation. This process requires distinct specialized functions in the head, body, and tail of the duct. These region-specific properties are maintained by distinct gene expression profiles which are governed by transcription factor networks, non-coding RNAs, and other factors. Materials and methods: We used genome-wide protocols including DNase-seq, RNA-seq and ChIP-seq to characterize open (active) chromatin, the transcriptome and occupancy of specific transcription factors (TFs) respectively, in caput, corpus, and cauda segments of adult human epididymis tissue and primary human epididymis epithelial (HEE) cell cultures derived from them. RNA-seq following TF depletion or activation, combined with gene ontology analysis also determined TF targets. Results: Among regional differentially expressed transcripts were epithelial-selective transcription factors (TFs), microRNAs, and antiviral response genes. Caput-enriched TFs included hepatocyte nuclear factor 1 (HNF1) and the androgen receptor (AR), both of which were also predicted to occupy cis-regulatory elements identified as open chromatin in HEE cells. HNF1 targets were identified genome-wide using ChIP-seq, in HEE cells. Next, siRNA-mediated depletion of HNF1 revealed a pivotal role for this TF in coordinating epithelial water and solute transport in caput epithelium. The importance of AR in HEE cells was shown by AR ChIP-seq, and by RNA-seq after synthetic androgen (R1881) treatment. AR has a distinct transcriptional program in the HEE cells and likely recruits different co-factors (RUNX1 and CEBPβ) in comparison to those used in prostate epithelium. Discussion and conclusion: Our data identify many transcription factors that regulate the development and differentiation of HEE cells. Moreover, a comparison between immature and adult HEE cells showed key TFs in the transition to fully differentiated function of this epithelium. These data may help identify new targets to treat male infertility and have the potential to open new avenues for male contraception.
MeSH term(s)	Computational Biology/methods ; Epididymis/metabolism ; Gene Expression Profiling ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/genetics ; Hepatocyte Nuclear Factor 1/metabolism ; Humans ; Male ; Sperm Maturation/genetics ; Transcriptome/genetics
Chemical Substances	Hepatocyte Nuclear Factor 1 (126548-29-6)
Language	English
Publishing date	2019-05-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2696108-8
ISSN	2047-2927 ; 2047-2919
ISSN (online)	2047-2927
ISSN	2047-2919
DOI	10.1111/andr.12629
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Article: 6 Immunological aspects of ovarian follicle ovulation and corpus luteum formation in cattle

Rabiah, N. A. Al / Evans, A. C. O / McCormack, J / Browne, J. A / Lonergan, P / Fair, T

Reproduction, fertility, and development. 2021, v. 33, no. 2

2021

Abstract: Ovarian follicle ovulation and subsequent luteinization have been described as a controlled inflammatory event, comprising tissue damage and repair. To elaborate this further in cattle, the contribution of immune cells to dominant follicle luteinization, ...

Abstract	Ovarian follicle ovulation and subsequent luteinization have been described as a controlled inflammatory event, comprising tissue damage and repair. To elaborate this further in cattle, the contribution of immune cells to dominant follicle luteinization, ovulation, and corpus luteum formation was investigated. Ovulation in beef heifers was synchronized using an 8-day progesterone-based synchronization program. Heifers were slaughtered at a local abattoir at 5 timepoints (T): (T1) 24h before ovulation (n=10); (T2) 2h before ovulation (n=9); (T3) 6h after ovulation (n=10); (T4) 24h after ovulation (n=10); (T5) 72h after ovulation (n=10), and ovarian tissue was collected and returned to the laboratory on ice. Follicular fluid, theca, granulosa, and corpus luteum (CL) tissues were recovered by dissection and processed for analysis. The concentrations of a panel of cytokines were measured using an antibody-conjugated magnetic bead immunoassay. The abundance of T-lymphocytes, mast cells, neutrophils, eosinophils, monocytes, macrophages, and dendritic cells was determined by immunohistochemistry. The mRNA relative abundance of candidate genes, including angiogenic growth factors, adhesion factors, chemokines and cytokines, was determined by quantitative real-time PCR analysis. The resulting datasets were analysed using the linear mixed model procedure of SAS and data are presented as least squares means; reported differences were deemed significant at P≤0.05. The cytokines IFNy, IP-10, IL-10, IL-36RA, MCP-1, MIP-1a, MIP-1b, and VEGF-A were detected in follicular fluid. The concentrations (pg mL−1) of IL-10 and VEGF-A were significantly higher in T1 follicular fluid samples compared with T2 (7.70 vs. 0.86 and 2193.33 vs. 293.93, respectively). Although dendritic cells were the most abundant cells in bovine ovulatory follicular and early corpus luteum tissue at all time points (P<0.05), their numbers peaked in ovulatory (T2) thecal tissue (261.5 cells/mm2). The greatest number of neutrophils was identified in thecal tissue at T1 (45/mm2); thereafter, their numbers declined to 1.1/mm2 in CL tissue by T5. Similarly, the numbers of T-lymphocytes, mast cells, monocytes, and macrophages declined in CL tissue at T4 and T5. Candidate gene mRNA expression profiles appeared to be time- and tissue-specific; for example, IFNA was highest in the preovulatory granulosa tissue (T1), IL8 was highest in peri-ovulatory thecal tissue (T2), VEGFA and MMP9 were highest in the early CL tissue (T4 and T5), MMP1, TIMP1, and VCAM1 expression was highest in theca, granulosa, and CL tissue collected on or after ovulation (T2, T4, T5), expression of the prostaglandin-related genes PTGES and PTGS2 was lowest in CL tissue, and that of PTGIS was highest. The current findings support the hypothesis that ovulation in heifers is characterised by an initial proinflammatory cascade followed by a dramatic switch to tissue repair, growth, and remodelling, all occurring within a 72-h period and commencing with the LH surge. Our results highlight the roles of neutrophils, dendritic cells, and macrophages as the key actors in this process.
Keywords	T-lymphocytes ; adhesion ; beef ; corpus luteum ; data collection ; dissection ; eosinophils ; follicular fluid ; gene expression ; genes ; ice ; immunoassays ; immunohistochemistry ; interleukin-10 ; interleukin-8 ; luteinization ; macrophages ; magnetism ; monocytes ; neutrophils ; ovulation ; quantitative polymerase chain reaction ; slaughterhouses ; statistical models ; tissue repair ; vascular endothelial growth factor A
Language	English
Size	p. 110.
Publishing place	CSIRO Publishing
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1019913-5
ISSN	1448-5990 ; 1031-3613
ISSN (online)	1448-5990
ISSN	1031-3613
DOI	10.1071/RDv33n2Ab6
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Article ; Online: The Second Surge of COVID-19: Better Prepared and a Brighter Light at the End of the Tunnel.

Mont, M A / Backstein, D J / Browne, J A / Krebs, V E / Krueger, C A / Mason, J B / Taunton, M J / Callaghan, J J

The Journal of arthroplasty

2021 Volume 36, Issue 2, Page(s) 395–396

MeSH term(s)	COVID-19 ; Humans ; SARS-CoV-2
Language	English
Publishing date	2021-01-15
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2020.12.020
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Article ; Online: The Problem With Fragile Results.

Krueger, C A / Mont, M A / Backstein, D J / Browne, J A / Krebs, V E / Mason, J B / Taunton, M J / Callaghan, J J

The Journal of arthroplasty

2021 Volume 36, Issue 6, Page(s) 1847–1848

Language	English
Publishing date	2021-03-12
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2021.04.018
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Article ; Online: Real Time Conversations: Changes to the Letters to the Editor.

Krueger, C A / Backstein, D J / Browne, J A / Krebs, V E / Mason, J B / Mont, M A / Taunton, M J / Callaghan, J J

The Journal of arthroplasty

2021 Volume 36, Issue 7, Page(s) 2249

Language	English
Publishing date	2021-06-01
Publishing country	United States
Document type	Editorial
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2021.05.011
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Article ; Online: Erratum to 'Real Time Conversations: Changes to the Letters to the Editor [The Journal of Arthroplasty 36 (2021) 2249]'.

Krueger, C A / Backstein, D J / Browne, J A / Krebs, V E / Mason, J B / Mont, M A / Taunton, M J / Callaghan, J J

The Journal of arthroplasty

2021 Volume 36, Issue 10, Page(s) e2

Language	English
Publishing date	2021-08-06
Publishing country	United States
Document type	Published Erratum
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2021.07.009
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Article ; Online: COVID Will End But Telemedicine May be Here to Stay.

Krueger, C A / Mont, M A / Backstein, D J / Browne, J A / Krebs, V E / Mason, J B / Taunton, M J / Callaghan, J J

The Journal of arthroplasty

2021 Volume 36, Issue 3, Page(s) 789–790

MeSH term(s)	COVID-19 ; Humans ; SARS-CoV-2 ; Telemedicine
Language	English
Publishing date	2021-02-18
Publishing country	United States
Document type	Editorial
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2021.01.034
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