Progesterone-regulated secretion of the serpin-like proteins of the ovine and bovine uterus

Leslie, M.V.; Hansen, Peter J.

doi:10.1016/0039-128x(91)90022-n

Cited by 40 publications

(30 citation statements)

References 23 publications

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“…The first, UTMP, is the most abundant protein present in the pregnant ruminant uterus and is reported to have an immunosuppressive action (Segerson and Bazer 1989) allowing immunological tolerance of the conceptus by the maternal uterus. Concentrations of UTMP protein in cattle ULF are increased after long exposure to progesterone (Leslie and Hansen 1991) and in the present study there was a positive correlation between Day 3 post-ovulatory progesterone concentration and UTMP mRNA expression. However, in the uteri with larger conceptuses and greater UTMP expression there was also a greater IFNT exposure, although a recent study reported UTMP expression was not stimulated by IFNT in endometrial cell cultures, only by progesterone and oestrogen (Ulbrich et al 2009).…”

Section: Evaluation Of the Bovine Uterine Environmentsupporting

confidence: 75%

Evaluation of the uterine environment early in pregnancy establishment to characterise cows with a potentially superior ability to support conceptus survival

Ledgard

Meier

Peterson

2011

Reprod. Fertil. Dev.

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Abstract. During previous investigations, the capacity of the cow to secrete prostaglandin in response to oxytocin has been linked with pregnancy outcome. The objective of the present study was to evaluate the predictive value of prostaglandin release to identify groups of cows as potentially superior (SR, low prostaglandin release) or inferior (IR, high prostaglandin release) for pregnancy outcome and to utilise these cows to investigate factors that contribute to optimum uterine conditions for early pregnancy. Animals were synchronised and received an in vitro-derived blastocyst on Day 7 post-oestrus. Tissues (trophoblast and endometrial) and uterine luminal fluid (ULF) were recovered 10 days later. Pregnancy rates were 94 and 78% for SR and IR cows, respectively. Of the pregnant SR cows, 69% had larged conceptuses (.24 cm) in contrast to 43% IR of cows. IR cows with small conceptuses (,12 cm) had significantly lower mean Day 3 and 5 post-oestrous progesterone concentrations than cows with large conceptuses. The expression of factors involved in the prostaglandin pathway, pregnancy and conceptus development were analysed via quantitative RT-PCR and Western blot analysis. Investigation of 16 endometrial gene transcripts indicated no differences between IR and SR cows except for osteopontin expression which, in uteri with large conceptuses, was 2-fold greater in SR than IR cows (P ¼ 0.02). There was greater expression of CTGF, OXTR, PGES, PGHS2 and UTMP mRNA in uteri of SR and IR cows that had large compared with small conceptuses (P , 0.05). More IFNT protein was recovered in SR compared with IR ULF (P , 0.03). SR cows with large conceptuses had less TIMP2 and legumain protein in their gravid, compared with their non-gravid horns (P # 0.02) whereas IR cows did not. The predictive value of prostaglandin release in response to oxytocin challenge does not appear to be an effective indicator of subsequent pregnancy rates in cows. Differences between the two groups appear to be associated with subtle differences in progesterone and uterine protein concentrations that may be related to differences in conceptus size.

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Section: Evaluation Of the Bovine Uterine Environmentsupporting

confidence: 75%

Evaluation of the uterine environment early in pregnancy establishment to characterise cows with a potentially superior ability to support conceptus survival

Ledgard

Meier

Peterson

2011

Reprod. Fertil. Dev.

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“…Several authors have the expression of UTMP suggested to be regulated by progesterone: Amounts of UTMP in uterine flushings of ovariectomized ewes were greatly enhanced by subcutaneous administration of progesterone for 10 respectively 30 days when compared with the control group and immunhistochemical analysis indicated that the major site of UTMP localization was the glandular epithelium. In ovariectomized cows enhanced amounts of UTMP were not observed until after 30 days of progesterone treatment (Leslie and Hansen, 1991). Similar observations were made by Ing and coworkers (1989): progesterone treatment of ovariectomized ewes resulted in low levels of UTMP in uterine flushings, whereas increasing levels were observed after 14 and 30 days of progesterone administration.…”

Section: Uterine Milk Proteinsupporting

confidence: 87%

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

Klein¹,

Bauersachs²,

Ulbrich³

et al. 2006

Reprod. Fertil. Dev.

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Early embryonic development, implantation, and maintenance of a pregnancy are critically dependent on an intact embryo-maternal communication. So far, only few signals involved in this dialogue have been identified. In ruminants, interferon tau (IFN�) plays a key role in the process of maternal recognition of pregnancy by exhibiting antiluteolytic activity. Even though many experimental findings indicate a pivotal role of IFN� in the context of embryo-maternal communication in ruminants, a number of other systems may be involved. To identify genes induced in the bovine endometrium by the signaling of the embryo, a combination of subtracted cDNA libraries and cDNA array hybridization was applied. Monozygotic twin pairs (n = 5) were used as the biological model. Pregnancy was created in one twin by transferring two in vitro-produced embryos on Day 7 of the estrous cycle; the other twin received a sham embryo transfer. Pregnant and nonpregnant twins were slaughtered at Day 18; endometrial tissue samples were recovered and processed for transcriptome analysis as described (Bauersachs et al. 2005 J. Mol. Endocrinol. 34, 889-908). Screening of 4608 clones of two subtracted libraries revealed 90 different up-regulated genes and mRNAs, of which almost 50% are known to be stimulated by type I interferons. Among these interferon-stimulated genes, the ISG15 system is assumed to be of particular interest, and several components were studied in more detail using in situ hybridization. The pattern of mRNA expression suggests that modification of endometrial proteins through ISG15ylation plays a fundamental role during the pre-implantation period. A classification of the identified genes based on Gene Ontologies revealed the prevalence of genes involved in regulation of gene expression, cell communication, cell growth, cell differentiation, cell proliferation, and cell adhesion, and also the prevalence of genes with immune-related functions. These results underline the intense response of the endometrium to the presence of a conceptus, culminating in the preparation of the maternal environment for embryonic implantation. Further, for eleven selected genes the expression in the endometrium was quantified by the use of real-time RT-PCR. Overall, the results of quantitative RT-PCR and array hybridization correlated very well. To our knowledge this study provides the first holistic gene expression analysis of the bovine endometrium during the pre-implantation period. The results underline the importance of IFN� as an embryo-derived pregnancy recognition signal and depict the molecular mechanisms at the mRNA level underlying the intense embryo-maternal dialog taking place at Day 18 of gestation.

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“…Both forms have a common NH 2 -terminal amino acid sequence precursor (34) and have identical isoelectric points (pI Ͼ8.5) (37). These proteins are structurally related to bovine UTMP (75.9% homology) (38) and porcine uteroferrin-associated protein precursor (56.3% homology) (39). Our studies with allantoic fluid have at this stage only identified a single UTMP protein, and it is unclear whether both molecular mass forms are produced in the allantoic fluid.…”

Section: Discussionmentioning

confidence: 82%

Uterine Milk Protein, a Novel Activin-Binding Protein, Is Present in Ovine Allantoic Fluid1

et al. 1999

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Activins are pluripotent growth factors that have recently been shown to be present in placental and fetal membrane preparations. Our previous studies have identified and purified activin A from ovine amniotic and allantoic fluids. In this study, ligand blots of side fractions from the isolation of activin A from allantoic fluid suggested the presence of activin-binding proteins other than follistatin. Further purification of one of these fractions involved two sequential reverse phase HPLC steps and a Superose 12HR fractionation. SDS-PAGE revealed a single protein band of 55 kDa, which was identified by NH 2 -terminal sequencing as ovine uterine milk protein (UTMP), a member of the serine protease inhibitor (serpin) superfamily of proteins. Further binding studies, using ligand blot techniques and Superose 12HR fractionation in the presence of [ 125 I]activin, demonstrated UTMP to be an activin-binding protein with a lower affinity for activin than that of follistatin. A study of the specific binding behavior of UTMP to activin, using surface plasmon resonance, revealed an apparent equilibrium dissociation constant (K d ) of 49 Ϯ 25 nM, compared with the follistatin-activin K d of 379 Ϯ 51 pM. Similar to another activin-binding protein, ␣ 2 -macroglobulin, UTMP was unable to neutralize the bioactivity of activin in a bioassay based on the capacity of activin to inhibit the proliferation of an MPC-11 plasmacytoma cell line. The high concentrations of this protein in uterine fluid during pregnancy and its ability to bind activin suggest that UTMP may act as a low affinity, high capacity binding protein to sequester activin in the local uterine environment. (Endocrinology 140: [4745][4746][4747][4748][4749][4750][4751][4752] 1999) A CTIVIN, isolated initially for its capacity to stimulate FSH (1, 2), has been identified as a member of the transforming growth factor-␤ family and, as such, is involved in a diverse range of physiological processes, such as embryogenesis (3), spermatogonial mitosis (4), and erythropoiesis (5). The homo-or heterodimerization of two subunits, ␤ A and ␤ B , results in the formation of three different bioactive variants, termed activin A (␤ A ␤ A ), activin AB (␤ A ␤ B ), and activin B (␤ B ␤ B ) (1, 2), all of which have been isolated and characterized. More recently, three other putative activin ␤-subunits (␤ C , ␤ D , and ␤ E ) have been identified from messenger RNA preparations using PCR procedures (6 -8).Recent data indicate that some of these bioactive variants circulate in serum (9 -11), raising the question of how their pluripotent actions are limited to specific sites. In part this is achieved by the presence of a specific binding protein, follistatin (FS) (12-14), which can neutralize the majority of the actions of activin A. The possibility of other activin-binding proteins with the capacity to regulate the actions of these pluripotent molecules has not been extensively explored.Activin A is produced by the placenta and fetal amnion and chorion preparations (15-17) ...

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Progesterone-regulated secretion of the serpin-like proteins of the ovine and bovine uterus

Cited by 40 publications

References 23 publications

Evaluation of the uterine environment early in pregnancy establishment to characterise cows with a potentially superior ability to support conceptus survival

Evaluation of the uterine environment early in pregnancy establishment to characterise cows with a potentially superior ability to support conceptus survival

2 Identification of Genes Induced by the Conceptus in the Bovine Endometrium During the Pre-Implantation Period

Uterine Milk Protein, a Novel Activin-Binding Protein, Is Present in Ovine Allantoic Fluid1

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