Endocrine actions of interferon-tau in ruminants

Hansen, T. R.; Henkes, LK; Ashley, RL; Bott, RC; Antoniazzi, AQ; Han, Hao

doi:10.7313/upo9781907284991.026

Cited by 12 publications

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“…Very recently, IFNT was demonstrated to be released from the uterus into the circulation and to induce ISGs in the CL. Circulating IFNT is thought to initiate a peripheral antiviral response and to induce luteal resistance to PGFa via endocrine mechanisms contributing to longer-term survival of the CL and maintenance of pregnancy [15].…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Effects of Early Pregnancy with Human Interferon, Alpha 2 (IFNA2), on Gene Expression in Bovine Endometrium1

Bauersachs¹,

Ulbrich

Reichenbach

et al. 2012

Biology of Reproduction

109

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Interferon tau (IFNT), a type I IFN similar to alpha IFNs (IFNA), is the pregnancy recognition signal produced by the ruminant conceptus. To elucidate specific effects of bovine IFNT and of other conceptus-derived factors, endometrial gene expression changes during early pregnancy were compared to gene expression changes after intrauterine application of human IFNA2. In experiment 1, endometrial tissue samples were obtained on Day (D) 12, D15, and D18 postmating from nonpregnant or pregnant heifers. In experiment 2, heifers were treated from D14 to D16 of the estrous cycle with an intrauterine device releasing IFNA2 or, as controls, placebo lipid extrudates or PBS only. Endometrial biopsies were performed after flushing the uterus. All samples from both experiments were analyzed with an Affymetrix Bovine Genome Array. Experiment 1 revealed differential gene expression between pregnant and nonpregnant endometria on D15 and D18. In experiment 2, IFNA2 treatment resulted in differential gene expression in the bovine endometrium. Comparison of the data sets from both studies identified genes that were differentially expressed in response to IFNA2 but not in response to pregnancy on D15 or D18. In addition, genes were found that were differentially expressed during pregnancy but not after IFNA2 treatment. In experiment 3, spatiotemporal alterations in expression of selected genes were determined in uteri from nonpregnant and early pregnant heifers using in situ hybridization. The overall findings of this study suggest differential effects of bovine IFNT compared to human IFNA2 and that some pregnancy-specific changes in the endometrium are elicited by conceptus-derived factors other than IFNT.endometrium, hormone action, pregnancy, reproductive immunology, uterus

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Section: Introductionmentioning

confidence: 99%

Comparison of the Effects of Early Pregnancy with Human Interferon, Alpha 2 (IFNA2), on Gene Expression in Bovine Endometrium1

Bauersachs¹,

Ulbrich

Reichenbach

et al. 2012

Biology of Reproduction

109

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“…Second, IFNT increases uterine production of PGEs (PGE1 and PGE2) and PGE blocks the action of PGF at the CL, maintaining CL function (Ottobre et al, 1984;Silvia et al, 1984a, b;Wiltbank and Ottobre, 2003;Krishnaswamy et al, 2009;Weems et al, 2011Weems et al, , 2012Lee et al, 2012). Third, recent convincing evidence demonstrates that IFNT exits the uterine lumen and interacts directly with the CL and may directly block PGF action at the CL (Gifford et al, 2007;Oliveira et al, 2008;Bott et al, 2010;Hansen et al, 2010;Antoniazzi et al, 2013). Although it will not be possible in this manuscript to definitely select which of these endocrine mechanism(s) is most important in maintenance of the CL during early pregnancy, some perspective can be thought-provoking.…”

Section: Period II Blockade Of Luteolysis In Early Pregnancyday 18-2mentioning

confidence: 99%

“…In uterus, IFNT acts in a paracrine manner to prevent expression of estrogen receptor alpha and oxytocin receptor in endometrial luminal epithelium and superficial glandular epithelium, thereby altering release of luteolytic pulses of PGF (Spencer et al, 2007b). Interferon-tau also stimulates expression of specific genes, termed interferon-stimulated genes (Antoniazzi et al, 2013), in the uterus (Johnson et al, 1999) and in peripheral tissues such as the CL (Oliveira et al, 2008;Bott et al, 2010) and peripheral blood cells (Gifford et al, 2007;Shirasuna et al, 2012). Thus, circulating IFNT that escapes the uterine lumen might prevent CL regression by acting directly on CL and this action could be independent or synergistic with the actions of IFNT on uterine PGF secretion.…”

Section: Period II Blockade Of Luteolysis In Early Pregnancyday 18-2mentioning

confidence: 99%

Maintenance or regression of the corpus luteum during multiple decisive periods of bovinepregnancy

Wiltbank¹,

Meidan²,

Ochoa³

et al. 2016

Anim Reprod

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In ruminants, there are specific times during the estrous cycle or pregnancy when the corpus luteum (CL) may undergo regression. This review has attempted to summarize the physiological and cellular mechanisms involved in CL regression or maintenance during four distinct periods. The first period is near day 7 when animals that are ovulating after a period of low circulating progesterone (P4), such as first pubertal ovulation or first postpartum ovulation, are at risk of having a premature increase in Prostaglandin F2α (PGF) secreted from the uterus resulting in early CL regression and a short estrous cycle. The second period is when normal luteolysis occurs at day 18-25 of the cycle or when the CL is rescued by interferon-tau secreted by the elongating embryo. The uterine mechanisms that determine the timing of this luteolysis or the prevention of luteolysis have been generally defined. Induction and activation of endometrial E2 receptors result in induction of endometrial oxytocin receptors that can now be activated by normal pulses of oxytocin. Of particular importance is the observation that the primary mechanisms are only activated through local (ipsilateral) and not a systemic route due to transfer of PGF from the uterine vein to the ovarian artery. In addition at the CL level, studies are providing definition to the cellular and molecular mechanisms that are activated in response to uterine PGF pulses or pregnancy. The third period that is discussed occurs in the second month of pregnancy (day 28-60) when undefined mechanisms result in CL maintenance of an ipsilateral CL but regression of a contralateral (opposite side from pregnancy) CL. The final period that is discussed is regression of the CL just prior to parturition. Although, cortisol from the fetus appears to be the primary initiator of luteolysis, PGF seems to be the final signal that causes regression of the CL. Thus, in all four periods, regression of the CL is likely to be caused by the direct actions of PGF that is secreted from the uterus. The uterine mechanisms that result in secretion of PGF seem to be normally inhibited during the early luteal phase, making short luteal phases not a normal event, and are altered during early pregnancy (day 18-25) resulting in prevention of luteolysis. During much of pregnancy, the mechanisms that cause PGF secretion from the uterus in response to oxytocin are intact but luteolysis does not normally occur, perhaps due to lack of efficient utero-ovarian transfer of PGF.

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“…The main function of the CL both during the cycle and pregnancy is synthesis of progesterone (P4), which plays major roles in the regulation of the length of the estrous cycle and in the implantation of the blastocyst after fertilization [6]. During maternal recognition of pregnancy, the conceptus synthesizes and secretes interferon tau (IFNτ), which protects the CL and extends the estrous cycle [7]. In addition to its antiluteolytic effects, IFNτ increases expression of several IFN-stimulated genes (ISG), such as 2',5'-oligoadenylate synthetase (OAS1) and ubiquitin-like IFNstimulated gene 15-kDa protein (ISG15) in the uterus [8], mammary gland and CL [9] in cattle.…”

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confidence: 99%

Lysophosphatidic Acid Action in the Bovine Corpus Luteum -An <i>In Vitro</i> Study

Kowalczyk-Zięba

Boruszewska

Saulnier-Blache

et al. 2012

Journal of Reproduction and Development

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Abstract. We examined whether the CL is a site for lysophosphatidic acid (LPA) synthesis and/or a target for LPA action in the bovine reproductive tract. LPA concentrations in the CL tissue increased towards the end of the cycle and were stable during early pregnancy. No changes in the expression of LPA receptors (LPARs) occurred during the estrous cycle. The expressions of LPAR2 and LPAR4 on days 17-19 of pregnancy were higher than those on the respective days of the estrous cycle and higher than those on days 8-10 of pregnancy. LPA stimulated P4 synthesis via 3βHSD stimulation but did not modulate the interferon-tau (IFNτ) influence on P4 synthesis in steroidogenic cells. Moreover, we found LPA-dependent stimulation of IFNτ action on 2,5'-oligoadenylate synthase (OAS1) and ubiquitin-like IFN-stimulated gene 15-kDa protein (ISG15) expression. The present study demonstrated that the CL might be a site of LPA synthesis and target of LPA action in the bovine reproductive tract. We postulate that during the estrous cycle and early pregnancy, LPA exerts autocrine and paracrine effects on the CL mainly via LPAR2 and LPAR4. The stimulatory effect of LPA on P4 synthesis via 3βHSD stimulation and LPA-dependent stimulation of IFNτ action on OAS1 and ISG15 expression suggest that LPA is an additional auxiliary luteosupportive factor in steroidogenic cells. T he corpus luteum (CL) is an endocrine gland that is temporarily formed in the ovary and undergoes regression at the end of the estrous cycle [1]. After ovulation, it forms from the Graafian follicle, grows and vascularizes rapidly. The bovine CL consists of a variety of cell types including large and small luteal cells, endothelial cells, fibroblasts and immune cells [2,3]. In nonpregnant cows, the CL undergoes luteolysis and becomes nonfunctional around days 17-18 after ovulation [4,5]. The main function of the CL both during the cycle and pregnancy is synthesis of progesterone (P4), which plays major roles in the regulation of the length of the estrous cycle and in the implantation of the blastocyst after fertilization [6]. During maternal recognition of pregnancy, the conceptus synthesizes and secretes interferon tau (IFNτ), which protects the CL and extends the estrous cycle [7]. In addition to its antiluteolytic effects, IFNτ increases expression of several IFN-stimulated genes (ISG), such as 2',5'-oligoadenylate synthetase (OAS1) and ubiquitin-like IFNstimulated gene 15-kDa protein (ISG15) in the uterus [8], mammary gland and CL [9] in cattle. However, during maternal recognition of pregnancy, P4 is the main factor responsible for its successful establishment. Luteinizing hormone (LH) is the most important regulator of P4 synthesis [10,11]. The growth and development of the early CL is supported by many factors, including LH, PGs (PGE 2 and PGI 2 ), oxytocin, noradrenaline and growth factors [12][13][14][15]. The CL can also autoregulate the synthesis of P4 [16].Lysophosphatidic acid (LPA) has been shown to affect the reproductive processes in rats [17], pigs [1...

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Endocrine actions of interferon-tau in ruminants

Cited by 12 publications

References 0 publications

Comparison of the Effects of Early Pregnancy with Human Interferon, Alpha 2 (IFNA2), on Gene Expression in Bovine Endometrium1

Comparison of the Effects of Early Pregnancy with Human Interferon, Alpha 2 (IFNA2), on Gene Expression in Bovine Endometrium1

Maintenance or regression of the corpus luteum during multiple decisive periods of bovinepregnancy

Lysophosphatidic Acid Action in the Bovine Corpus Luteum -An <i>In Vitro</i> Study

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