Immunoregulatory Activity, Biochemistry, and Phylogeny of Ovine Uterine Serpin

Peltier, Morgan R.; Hansen, Peter J.

doi:10.1111/j.8755-8920.2001.450502.x

Cited by 18 publications

(16 citation statements)

References 58 publications

(67 reference statements)

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“…Interestingly, the ovine placenta expresses large numbers of aspartic proteinase inhibitor genes, termed pregnancyassociated glycoproteins (31), and the endometrial glands express large amounts of serine protease inhibitors, termed serpins or uterine milk proteins (32), that could regulate the activity of endometrial CTS identified in the present study. Therefore, the molecular control of expression of CTS in the ovine endometrium may play an important role in establishing a regulatory network of multiple proteolytic enzymes responsible for ECM remodeling during implantation and placentation.…”

Section: Discussionmentioning

confidence: 65%

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

2005

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Cathepsins (CTS) are peptidases that have biological roles in degrading extracellular matrix, catabolism of intracellular proteins, and processing of prohormones. Expression of CTSB, CTSD, CTSH, CTSK, CTSL, CTSS, and CTSZ genes was detected in the endometria of cyclic and early pregnant ewes with distinct temporal and spatial expression patterns. In the d 18 and 20 conceptus, expression of CTSB, CTSD, CTSL, and CTSZ mRNA was detected in the trophectoderm. Of particular note, CTSL mRNA was the most abundant CTS mRNA in the ovine endometrium and detected only in the luminal epithelium and superficial glandular epithelium of cyclic and pregnant ewes. CTSL mRNA increased 8-fold between d 10 and 18 in endometria of pregnant ewes, whereas it declined between d 14 and 16 in cyclic ewes. CTSL protein was also detected in conceptus trophectoderm, and pro-CTSL was detected in uterine flushings from ewes between d 12 and 16 of pregnancy. In ovariectomized and catheterized ewes, CTSL mRNA in the endometrium was increased by progesterone and intrauterine injections of ovine interferon (IFN)tau. Other endometrial CTS genes were also regulated by progesterone alone (CTSB, CTSK, CTSS, and CTSZ) or progesterone and IFNtau (CTSH, CTSK, CTSS, and CTSZ). These results indicate that CTS of endometrial and conceptus origin may regulate endometrial remodeling and conceptus implantation, endometrial CTS genes are regulated by ovarian and placental hormones, and CTSL is a novel IFNtau-stimulated gene expressed only in luminal epithelium and superficial glandular epithelium of the endometrium.

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Section: Discussionmentioning

confidence: 65%

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

2005

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“…The two best-characterized GE secretory products are the ovine uterine milk proteins (UTMP), also termed ovine uterine serpins, and OPN. UTMPs are members of the serpin family of serine protease inhibitors [72] and serve as excellent markers for endometrial secretory capacity during pregnancy in sheep [73][74][75]. In pregnant sheep, UTMP mRNA expression is restricted to GE and not in LE or sGE.…”

Section: Uterine Gland Secretionsmentioning

confidence: 99%

Conceptus signals for establishment and maintenance of pregnancy

Spencer

2004

Animal Reproduction Science

164

202

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Establishment and maintenance of pregnancy results from signaling by the conceptus (embryo/fetus and associated extraembryonic membranes) and requires progesterone produced by the corpus luteum (CL). In most mammals, hormones produced by the trophoblast maintain progesterone production by acting directly or indirectly to maintain the CL. In domestic animals (ruminants and pigs), hormones from the trophoblast are antiluteolytic in that they act on the endometrium to prevent uterine release of luteolytic prostaglandin F2 alpha (PGF). In cyclic and pregnant sheep, progesterone negatively autoregulates expression of the progesterone receptor (PR) gene in the endometrial luminal (LE) and superficial glandular epithelium (GE). Available evidence in cyclic sheep indicates that loss of the PR is closely followed by increases in epithelial estrogen receptors (ER) and then oxytocin receptors (OTR), allowing oxytocin to induce uterine release of luteolytic PGF pulses. In pregnant sheep, the conceptus trophoblast produces interferon tau (IFN tau) that acts on the endometrium to inhibit transcription of the ER alpha gene directly and the OTR gene indirectly to abrogate development of the endometrial luteolytic mechanism. Subsequently, sequential, overlapping actions of progesterone, IFN tau, placental lactogen (PL) and growth hormone (GH) comprise a hormonal servomechanism that regulates endometrial gland morphogenesis and terminal differentiated function to maintain pregnancy in sheep. In pigs, the conceptus trophoblast produces estrogen that alters the direction of PGF secretion from an endocrine to exocrine direction, thereby sequestering luteolytic PGF within the uterine lumen. Conceptus estrogen also increases expression of fibroblast growth factor 7 (FGF-7) in the endometrial LE that, in turn, stimulates proliferation and differentiated functions of the trophectoderm, which expresses the FGF-7 receptor. Strategic manipulation of these physiological mechanisms can offer therapeutic schemes to improve uterine capacity, conceptus survival and reproductive health.

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“…UTMP is produced from uterine glandular epithelial cells and is a member of the serpin superfamily of proteinase inhibitors that exhibit weak antiproteinase activity but inhibit a wide range of lymphocyte functions (Ing et al 1989, Peltier & Hansen 2001. Consequently, UTMP is thought to be important in the inhibition of maternal immune responses directed against antigens expressed on the foeto-placental unit (Hansen 2007).…”

Section: Utmp Uterine Serpinmentioning

confidence: 99%

Immunoendocrine aspects of endometrial function and implantation

Lea

Sandra²

2007

Reproduction

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Effective ovarian and uterine function relies on a complex interplay between the endocrine and immune systems. It is generally accepted that in reproductive tissues, oestradiol and progesterone have pro-and anti-inflammatory activities respectively and, in this regard, the paracrine effects of the sex steroids on the ovary are similar to the endocrine effects on the uterus. Ovarian leukocyte recruitment and cytokine release are central to follicle development, ovulation and corpus luteum function. At the uterine level, the cyclical changes in sex steroids regulate the number and distribution of endometrial and decidual immune cells as well as other immune signalling and surveillance factors. The uterine mucosa is unique, in that it must tolerate sperm and the allogeneic blastocyst in a way that does not compromise uterine immune surveillance against bacteria, yeast and viruses. Crosstalk between the sex steroids and immune mediators (systemic and local) are central to these functions, and this article will review these mechanisms and their importance for successful reproductive function and pregnancy success.

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Immunoregulatory Activity, Biochemistry, and Phylogeny of Ovine Uterine Serpin

Cited by 18 publications

References 58 publications

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

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

Conceptus signals for establishment and maintenance of pregnancy

Immunoendocrine aspects of endometrial function and implantation

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