scholarly journals Interferon-tau and fertility in ruminants

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. F33-F43 ◽  
Author(s):  
N Forde ◽  
P Lonergan
Keyword(s):  
Prostaglandin F2α ◽  
Threshold Level ◽  
Type I ◽  
Interferon Tau ◽  
Uterine Endometrium ◽  
Domestic Ruminants ◽  
Oxytocin Receptors ◽  
Pregnancy Recognition ◽  
Maternal Recognition Of Pregnancy ◽  
Primary Agent

Establishment of pregnancy in domestic ruminants includes pregnancy recognition signalling by the conceptus, implantation and placentation. Despite the high fertilisation success rate in ruminants, a significant amount of embryo loss occurs, primarily during early gestation. Interferon-tau (IFNT), a type I interferon that is exclusively secreted by the cells of the trophectoderm of the ruminant conceptus, has been recognised as the primary agent for maternal recognition of pregnancy in ruminants. It produces its antiluteolytic effect on the corpus luteum by inhibiting the expression of oxytocin receptors in the uterine epithelial cells, which prevents pulsatile, luteolytic secretion of prostaglandin F2α by the uterine endometrium. While the importance of IFNT in maternal recognition of pregnancy and prevention of luteolysis in ruminants is unequivocal, important questions, for example, relating to the threshold level of IFNT required for pregnancy maintenance, remain unanswered. This paper reviews data linking IFNT with measures of fertility in ruminants.

Interferon, the oxytocin receptor and the maternal recognition of pregnancy in ruminants and non-ruminants: a comparative approach

1995 ◽  
Vol 7 (3) ◽  
pp. 313 ◽  
Author(s):  
AP Flint
Keyword(s):  
Roe Deer ◽  
Oxytocin Receptor ◽  
Comparative Approach ◽  
Type I ◽  
Embryonic Diapause ◽  
Domestic Pig ◽  
Interferon Tau ◽  
Characteristic Type ◽  
Domestic Ruminants ◽  
Maternal Recognition Of Pregnancy

Ruminant and non-ruminant members of the Artiodactyla appear to use different mechanisms for the maternal recognition of pregnancy. In ruminants, the trophoblast of the developing blastocyst produces a characteristic Type I interferon of the interferon-tau family; this acts by blocking endometrial synthesis of the oxytocin receptor. A similar mechanism applies to domestic ruminants (sheep, cow, goat) and deer. In roe deer, which have embryonic diapause and are monoestrus, there is no requirement for a pre-implantation blastocyst signal to ensure maternal recognition of pregnancy. This paper compares the mechanisms leading to the maternal recognition of pregnancy in ruminants with that suggested to occur in a non-ruminant (the domestic pig).

scholarly journals The Importance of Interferon-Tau in the Diagnosis of Pregnancy

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Alicja Kowalczyk ◽  
Ewa Czerniawska-Piątkowska ◽  
Marcjanna Wrzecińska
Keyword(s):  
Dairy Cattle ◽  
Specific Protein ◽  
Type I ◽  
Reproductive Disorders ◽  
Interferon Tau ◽  
Interferon Stimulated Genes ◽  
Genes Encoding ◽  
Pregnancy Status ◽  
New Type ◽  
Pregnancy Recognition

Several decades of improving dairy cattle towards unilateral utilization of dairy cattle led to enormous progress in the field of milk yield; however, it resulted in a number of unfavorable features, such as reproductive disorders, increased calf mortality, and reduced health. Most cases of embryo loss and/or lost pregnancies occur during the first four to five weeks of gestation; accurate detection for pregnancy during this period is likely to contribute to an improvement in gestation rates. A specific protein, interferon-tau (IFNT), stimulates interferon-stimulated genes (ISGs), and their expression increases during gestation within 21 days after insemination. In bovines, the early conceptus undergoes a phase of rapid growth and elongation before implantation, the latter occurring 2–3 weeks after fertilization. IFNT acts mainly in the endometrium of the luminal epithelium. It is a new type I interferon that regulates several genes encoding uterine-derived factors. They are crucial in the processes of preparing the uterus for placenta attachment, modifying the uterine immune system, and regulating early fetal development. Because IFNT is expressed and induces ISGs in the endometrium during pregnancy recognition, it was reasoned that surrogate markers for pregnancy or IFNT might be present in the blood and provide an indicator of pregnancy status in cattle.

Pregnancy recognition and conceptus implantation in domestic ruminants: roles of progesterone, interferons and endogenous retroviruses

2007 ◽  
Vol 19 (1) ◽  
pp. 65 ◽  
Author(s):  
Thomas E. Spencer ◽  
Greg A. Johnson ◽  
Fuller W. Bazer ◽  
Robert C. Burghardt ◽  
Massimo Palmarini
Keyword(s):  
Receptor Gene ◽  
Cathepsin L ◽  
Prostaglandin F2α ◽  
Endogenous Retroviruses ◽  
Oxytocin Receptor Gene ◽  
Domestic Ruminants ◽  
Cell Proliferation And Differentiation ◽  
New Information ◽  
Conceptus Development ◽  
Pregnancy Recognition

The present review highlights new information on pregnancy recognition and conceptus development and implantation in sheep with respect to regulation by progesterone, interferons and endogenous retroviruses. After formation of the corpus luteum, progesterone acts on the endometrium and stimulates blastocyst growth and elongation to a filamentous conceptus (embryo/fetus and associated extra-embryonic membranes). The envelope of endogenous retroviruses related to Jaagsiekte sheep retroviruses appears to intrinsically regulate mononuclear trophectoderm cell proliferation and differentiation into trophoblast giant binucleate cells. The mononuclear trophectoderm cells of elongating sheep conceptuses secrete interferon-τ, which acts on the endometrium to prevent development of the luteolytic mechanism by inhibiting transcription of the gene for the oestrogen receptor α in the luminal and superficial ductal glandular epithelia. These actions prevent oestrogen-induced transcription of the oxytocin receptor gene and, therefore, oxytocin-induced luteolytic pulses of prostaglandin F2α. Progesterone downregulation of its receptors in luminal and glandular epithelia correlates temporally with a reduction in anti-adhesive mucin 1and induction of secreted galectin 15 (LGALS15) and secreted phosphoprotein 1, which are proposed to regulate trophectoderm proliferation and adhesion. Interferon-τ acts on the endometrial lumenal epithelium to induce WNT7A and to stimulate LGALS15, cathepsin L and cystatin C, which are candidate regulators of conceptus development and implantation. The number of potential contributors to maternal recognition and establishment of pregnancy continues to grow and this highlights our limited appreciation of the complexity of the key molecules and signal transduction pathways that intersect during these key developmental processes. The goal of improving reproductive efficiency by preventing embryonic losses that occur during the peri-implantation period of pregnancy in domestic ruminants provides the challenge to increase our knowledge of endometrial function and conceptus development.

scholarly journals Profiles of prostaglandin F2α metabolite in dairy cattle during luteal regression and pregnancy: implications for corpus luteum maintenance†

2019 ◽  
Vol 101 (1) ◽  
pp. 76-90 ◽  
Author(s):  
Megan A Mezera ◽  
Caleb S Hamm ◽  
Caio A Gamarra ◽  
Rodrigo S Gennari ◽  
Alexandre B Prata ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Peak Concentration ◽  
Prostaglandin F2α ◽  
Interferon Tau ◽  
Similar Frequency ◽  
Luteal Regression ◽  
Oxytocin Receptors ◽  
Bovine Corpus Luteum ◽  
Reproductive Losses

Abstract Mechanisms of bovine corpus luteum (CL) maintenance during the second month of pregnancy have not been adequately investigated, despite significant reproductive losses. In the first month, interferon-tau is believed to suppress oxytocin-stimulated prostaglandin F2α (PGF) production, yet there are conflicting reports of circulating PGF metabolite (PGFM). In this study, characterization of PGFM and P4 occurred through continuous bihourly blood sampling in cows undergoing CL regression (day 18–21, n = 5), and during the first (day 18–21, n = 5) and second month (day 47–61; n = 16) of pregnancy. Cattle in the second month were assigned to control (n = 8) or oxytocin treatment (n = 8; three pulses to mimic luteolysis) to evaluate if oxytocin receptors were active. All cows but one (which had elevated PGFM prior to oxytocin treatment) maintained the pregnancy. Basal PGFM concentrations were low (11.6 ± 0.7 pg/mL) in the first month but increased 2.54-fold in the second month. Few (0.26 ± 0.12 pulses/day) PGFM pulses with low peak concentrations (28.8 ± 3.1 pg/mL) were observed during the first month of pregnancy, similar to cows not undergoing regression. However, in the second month, frequency (1.10 ± 0.26 pulses/day) and peak concentration (67.2 ± 5.0 pg/mL) of PGFM pulses increased, displaying similar frequency but lower peak PGFM than seen in regression (1.44 ± 0.14 pulses/day; 134.5 ± 18.9 pg/mL). Oxytocin treatment increased likelihood of PGFM pulses post-treatment and increased peak concentration (89.7 ± 10.1 pg/mL) in cows during the second month. Thus, cows have more PGFM pulses during second than first month of pregnancy, possibly induced by endogenous oxytocin, indicating suppression of PGF production is an important mechanism for CL maintenance during first but not second month of pregnancy.

scholarly journals Paracrine and endocrine actions of interferon tau (IFNT)

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. F45-F59 ◽  
Author(s):  
Thomas R Hansen ◽  
Leticia D P Sinedino ◽  
Thomas E Spencer
Keyword(s):  
Mononuclear Cells ◽  
Endocrine Effects ◽  
Interferon Tau ◽  
Peripheral Blood Mononuclear ◽  
Prostaglandin F2 Alpha ◽  
Oxytocin Receptors ◽  
Specific Manner ◽  
Pregnancy Status ◽  
A Cell ◽  
Pregnancy Recognition

This review focuses on the paracrine and endocrine actions of interferon tau (IFNT) during pregnancy recognition and establishment in ruminants. Pregnancy recognition involves the suppression of the endometrial luteolytic mechanism by the conceptus to maintain progesterone production by the corpus luteum (CL). The paracrine antiluteolytic effects of conceptus-derived IFNT inhibit upregulation of oxytocin receptors in the endometrial epithelia of the uterus, thereby preventing the production of luteolytic prostaglandin F2 alpha (PGF2α) pulses. In the endometrium, IFNT induces or upregulates a large number of classical IFN-stimulated genes (ISGs) and regulates expression of many other genes in a cell-specific manner that are likely important for conceptus elongation, implantation and establishment of pregnancy. Further, IFNT has endocrine effects on extrauterine cells and tissues. In sheep, IFNT induces luteal resistance to PGF2α, thereby ensuring survival of the CL for maintenance of pregnancy. The ISGs induced in circulating peripheral blood mononuclear cells by IFNT may also be useful as an indicator of pregnancy status in cattle. An increased knowledge of IFNT and ISGs is important to improve the reproductive efficiency in ruminants.

scholarly journals Pregnancy and interferon tau regulate RSAD2 and IFIH1 expression in the ovine uterus

Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 285-295 ◽  
Author(s):  
Gwonhwa Song ◽  
Fuller W Bazer ◽  
Thomas E Spencer
Keyword(s):  
Immune Cells ◽  
Transcriptional Profiling ◽  
Immune Defense ◽  
Type I ◽  
Uterine Receptivity ◽  
Antiviral Protein ◽  
Interferon Tau ◽  
Independent Manner ◽  
Uterine Endometrium ◽  
A Cell

Radical S-adenosyl methionine domain containing 2 (RSAD2) encodes a cytoplasmic antiviral protein induced by interferons (IFN). Interferon-induced with helicase C domain 1 (IFIH1) is a RNA helicase involved in innate immune defense against viruses, growth suppression, and apoptosis. Interferon tau (IFNT), a Type I IFN produced by the peri-implantation ruminant conceptus, acts on the uterine endometrium to signal pregnancy recognition and promote receptivity to implantation. Transcriptional profiling identifiedRSAD2andIFIH1as IFNT regulated genes in the ovine uterine endometrium. This study tested the hypothesis thatRSAD2andIFIH1were induced in the endometrium in a cell type-specific manner by IFNT from the conceptus during early pregnancy. EndometrialRSAD2andIFIH1mRNA increased between days 12 and 16 of pregnancy, but not of the estrous cycle. In pregnant ewes,RSAD2andIFIH1mRNAs increased in endometrial glands, and stroma and immune cells, but not in the luminal epithelium. Neither gene was expressed in the trophectoderm of day 18 or 20 conceptuses. Progesterone (P4) treatment of ovariectomized ewes did not induce expressionRSAD2orIFIH1mRNA in the endometrium; however, intrauterine injections of IFNT induced expression ofRSAD2andIFIH1mRNA in endometria of ewes treated with P4, as well as in ewes treated with P4 and the progesterone receptor antagonist, ZK 136,317. These results indicate that conceptus IFNT induces bothRSAD2andIFIH1in a P4-independent manner in the ovine uterine endometrium. These two IFNT-stimulated genes are proposed to have biological roles in the establishment of uterine receptivity to the conceptus during implantation through induction of an antiviral state and modulation of local immune cells in the endometrium.

Maternal recognition of pregnancy in the horse: a mystery still to be solved

2011 ◽  
Vol 23 (8) ◽  
pp. 952 ◽  
Author(s):  
C. Klein ◽  
M. H. T. Troedsson
Keyword(s):  
Prostaglandin F2α ◽  
Cyclooxygenase 2 ◽  
Microarray Experiments ◽  
Luteal Function ◽  
Domestic Species ◽  
Prostaglandin Release ◽  
Conceptus Development ◽  
Immunological Rejection ◽  
Pregnancy Recognition ◽  
Maternal Recognition Of Pregnancy

Maternal recognition of pregnancy in the horse is the sum of events leading to maintenance of pregnancy; in a narrow sense, maternal recognition of pregnancy refers to the physiological process by which the lifespan of the corpus luteum is prolonged. The horse is one of the few domestic species in which the conceptus-derived pregnancy recognition signal has not been identified. The presence of the conceptus reduces pulsatile prostaglandin F2α secretion by the endometrium during early gestation in the mare, partly attributed to the reduced expression of cyclooxygenase-2. Cyclooxygenase-2 has therefore been suggested as one of the regulators of endometrial prostaglandin F2α release modified by the antiluteolytic factor secreted by the conceptus. In addition, altered oxytocin responsiveness has been implicated in the adjustment of prostaglandin release in pregnant mares. While conceptus mobility has proven to be essential for establishment of pregnancy, conceptus-derived oestrogens and prostaglandins, principally prostaglandin E2, have not been confirmed as the critical antiluteolytic factor. Various ways to induce prolonged luteal function in the non-pregnant mare will be highlighted in the current review, specifically, how they may pertain to the process of maternal recognition of pregnancy. Furthermore, recently published microarray experiments comparing the transcriptome of pregnant and non-pregnant endometria and different stages of conceptus development will be reviewed. Findings include the prevention of conceptus adhesion, the provision of nutrients to the conceptus and the avoidance of immunological rejection, among others.

scholarly journals Transcriptional control of IFNT expression

Reproduction ◽  
2017 ◽  
Vol 154 (5) ◽  
pp. F21-F31 ◽  
Author(s):  
Toshihiko Ezashi ◽  
Kazuhiko Imakawa
Keyword(s):  
Transcription Factor ◽  
Binding Site ◽  
Intracellular Signaling ◽  
Transcriptional Control ◽  
Proximal Region ◽  
Type I ◽  
Interferon Tau ◽  
Specific Expression ◽  
Uterine Endometrium ◽  
Separate Site

Once interferon-tau (IFNT) had been identified as a type I IFN in sheep and cattle and its functions were characterized, numerous studies were conducted to elucidate the transcriptional regulation of this gene family. Transfection studies performed largely with human choriocarcinoma cell lines identified regulatory regions of the IFNT gene that appeared responsible for trophoblast-specific expression. The key finding was the recognition that the transcription factor ETS2 bound to a proximal region within the 5′UTR of a bovine IFNT and acted as a strong transactivator. Soon after other transcription factors were identified as cooperative partners. The ETS2-binding site and the nearby AP1 site enable response to intracellular signaling from maternal uterine factors. The AP1 site also serves as a GATA-binding site in one of the bovine IFNT genes. The homeobox-containing transcription factor, DLX3, augments IFNT expression combinatorially with ETS2. CDX2 has also been identified as transactivator that binds to a separate site upstream of the main ETS2 enhancer site. CDX2 participates in IFNT epigenetic regulation by modifying histone acetylation status of the gene. The IFNT downregulation at the time of the conceptus attachment to the uterine endometrium appears correlated with the increased EOMES expression and the loss of other transcription coactivators. Altogether, the studies of transcriptional control of IFNT have provided mechanistic evidence of the regulatory framework of trophoblast-specific expression and critical expression pattern for maternal recognition of pregnancy.

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.

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