Cathepsins in the Ovine Uterus: Regulation by Pregnancy, Progesterone, and Interferon Tau

Song, Gwonhwa; Spencer, Thomas E.; Bazer, Fuller W.

doi:10.1210/en.2005-0768

Cited by 88 publications

(90 citation statements)

References 42 publications

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“…Further, treatment of ovine endometrial LE and BEND cells with recombinant ovine IFNT induced RSAD2 and IFIH1 expression without a requirement for serum or P4 in the medium. In contrast, IFNT induction of several non-classical IFN-stimulated genes, such as LGALS15 (galectin 15), CTSL (cathespin L), and CST3 (cystatin C), in endometrial LE and sGE is dependent on P4 (Gray et al 2004, Song et al 2005, which is hypothesized to involve P4 downregulation of the PGR in those epithelia (Spencer et al 2004c, Gray et al 2006.…”

Section: Discussionmentioning

confidence: 99%

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

Song¹,

Bazer²,

Spencer³

2007

Reproduction

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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 identified RSAD2 and IFIH1 as IFNT regulated genes in the ovine uterine endometrium. This study tested the hypothesis that RSAD2 and IFIH1 were induced in the endometrium in a cell type-specific manner by IFNT from the conceptus during early pregnancy. Endometrial RSAD2 and IFIH1 mRNA increased between days 12 and 16 of pregnancy, but not of the estrous cycle. In pregnant ewes, RSAD2 and IFIH1 mRNAs 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 expression RSAD2 or IFIH1 mRNA in the endometrium; however, intrauterine injections of IFNT induced expression of RSAD2 and IFIH1 mRNA 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 both RSAD2 and IFIH1 in 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.

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Section: Discussionmentioning

confidence: 99%

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

Song¹,

Bazer²,

Spencer³

2007

Reproduction

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“…As depicted in Fig. 1, temporal and spatial analyses of gene expression revealed that galectin 15 (LGALS15), cystatin C (CST3), and cathepsin L (CTSL) expression is initiated in the endometrial LE by day 12 and maintained to day 14 in both cyclic and pregnant ewes (Gray et al 2004, Song et al 2005, 2006a. Those genes are no longer expressed by day 16 in cyclic ewes, but their expression is further stimulated by IFNT from the conceptus in pregnant ewes.…”

Section: Hormonal Regulation Of Endometrial Function and Conceptus Dementioning

confidence: 99%

“…Recent studies found that LGALS15, CTSL, and CST3 are induced by progesterone and stimulated further by IFNT (Gray et al 2004, Song et al 2005, 2006a, Satterfield et al 2006. In most mammalian uteri, progesterone receptors (PGR) are expressed in endometrial epithelia and stroma during the early to mid-luteal phase, allowing direct regulation (induction or repression) of genes by progesterone.…”

Section: Pgr Regulation and Endometrial Gene Expressionmentioning

confidence: 99%

“…In pregnant ewes ( Fig. 1), loss of PGR in endometrial epithelia is associated with a reduction in anti-adhesive MUC1 (mucin glycoprotein 1) and onset LGALS15, CTSL, and CST3 expression in the LE (Gray et al 2004, Song et al 2005, 2006a, Satterfield et al 2006 and SPP1 (secreted phosphoprotein 1 or osteopontin), STC1 (stanniocalcin), and UTMP (uterine milk proteins or serpins) expression in the GE (Johnson et al Embryo-maternal communication 2000b, Stewart et al 2000, Song et al 2006b. One understudied area is what controls expression of the PGR and how PGR regulates transcription of target genes in a cell-specific manner within the uterus.…”

Section: Pgr Regulation and Endometrial Gene Expressionmentioning

confidence: 99%

“…2). Transcriptional profiling of human U3A (STAT1 null) cells and ovine endometrium treated with IFNT were used to discover novel ISGs in the endometrial LE during pregnancy including WNT7A (wingless-type MMTV integration site family, member 7A), LGALS15, CTSL, and CST3 (Kim et al 2003, Song et al 2005, 2006a, Gray et al 2006. The expression patterns of novel and classical ISGs are summarized in Figs 1 and 2.…”

Section: Ifnt and The Jak-stat-irf Pathwaymentioning

confidence: 99%

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Genes involved in conceptus–endometrial interactions in ruminants: insights from reductionism and thoughts on holistic approaches

Spencer¹,

Sandra²,

Wolf³

2008

Reproduction

274

253

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This review summarizes new knowledge on expression of genes and provides insights into approaches for study of conceptus-endometrial interactions in ruminants with emphasis on the peri-implantation stage of pregnancy. Conceptus-endometrial interactions in ruminants are complex and involve carefully orchestrated temporal and spatial alterations in gene expression regulated by hormones from the ovary and conceptus. Progesterone is the hormone of pregnancy and acts on the uterus to stimulate blastocyst survival, growth, and development. Inadequate progesterone levels or a delayed rise in progesterone is associated with pregnancy loss. The mononuclear trophectoderm cells of the elongating blastocyst synthesize and secrete interferon-t (IFNT), the pregnancy recognition signal. Trophoblast giant binucleate cells begin to differentiate and produce hormones including chorionic somatomammotropin 1 (CSH1 or placental lactogen). A number of genes, induced or stimulated by progesterone, IFNT, and/or CSH1 in a cell-specific manner, are implicated in trophectoderm adhesion to the endometrial luminal epithelium and regulation of conceptus growth and differentiation. Transcriptional profiling experiments are beginning to unravel the complex dynamics of conceptus-endometrial interactions in cattle and sheep. Future experiments should incorporate physiological models of pregnancy loss and be complemented by metabolomic studies of uterine lumen contents to more completely define factors required for blastocyst survival, growth, and implantation. Both reduction and holistic approaches will be important to understand the multifactorial phenomenon of recurrent pregnancy loss and provide a basis for new strategies to improve pregnancy outcome and reproductive efficiency in cattle and other domestic animals.

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Analysis of legumain and cystatin 6 expression at the maternal-fetal interface in pigs

et al. 2013

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Cathepsins (CTSs), a family of lysosomal cysteine proteases, and their inhibitors, cystatins (CSTs), play a critical role in endometrial and placental tissue remodeling during the establishment and maintenance of pregnancy in many species including rodents, sheep, cow, and pigs. In this study, we determined expression of legumain (LGMN), a cathepsinmember, and its inhibitor, CST6, at the maternal-fetal interface in pigs. Expression of both LGMN and CST6 mRNAs increased during mid- to late pregnancy in the uterine endometrium. LGMN and CST6 mRNAs localized to luminal epithelial cells (LE) and glandular epithelial cells (GE) and to the chorionic membrane (CM), with a strong intensity in GE and the CM for LGMN and in the CM for CST6 during pregnancy. LGMN protein was detected at molecular weights (MW) of approximately 50,000 and 37,000, and the abundance of the37,000-MW LGMN protein increased during mid- to latepregnancy. CST6 protein was also highly expressed in the uterine endometrium in mid- to latepregnancy. LGMN protein localized to LE, GE, and the CM during pregnancy. LGMN and CST6 were aberrantly expressed in the uterine endometrium from gilts with somatic cell nuclear transfer-derived conceptuses at term compared to those of gilts carrying conceptuses derived from natural mating. These results demonstrated that LGMN and CST6 were expressed in the uterine endometrium in a cell-type and stage-specific manner, suggesting that the LGMN and CST6 system at the maternal-fetal interface may play an important role in the establishment and maintenance of pregnancy in pigs.

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Cathepsins in the Ovine Uterus: Regulation by Pregnancy, Progesterone, and Interferon Tau

Cited by 88 publications

References 42 publications

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

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

Genes involved in conceptus–endometrial interactions in ruminants: insights from reductionism and thoughts on holistic approaches

Analysis of legumain and cystatin 6 expression at the maternal-fetal interface in pigs

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