In Exp. I, 0.5 mg oestradiol or vehicle (0.5 ml absolute ethanol + 0.5 ml 0.9% NaCl) was injected i.v. at 08:00 h on Day 14 (onset of oestrus = Day 0). Blood samples were obtained via a jugular catheter at 30 and 1 min before oestradiol and every 30 min for 10 h afterwards. Plasma was obtained and assayed for 15-keto-13,14-dihydro-PGF-2 alpha (PGFM) by radioimmunoassay. Before oestradiol, PGFM basal values were higher (P less than 0.01) in pregnant (N = 10) than nonpregnant (N = 6) ewes (193 +/- 30 vs 67 +/- 8 pg/ml). However, at 4-10 h after oestradiol, pregnant ewes (N = 5) had less variable (P less than 0.01) PGFM values than did nonpregnant ewes (N = 5). In Exp II, conceptus secretory proteins (CSP) were obtained by pooling medium from cultures of Day-16 sheep conceptuses (N = 40). Ewes received 750 micrograms CSP + 750 micrograms plasma protein (N = 6) or 1500 micrograms plasma protein (N = 6) per uterine horn at 08:00 h and 18:00 h on Days 12-14. All ewes received 0.5 mg oestradiol at 08:00 h on Day 14 and blood samples were collected as in Exp. I and assayed for PGFM. On Day 15, 3 ewes in each group received 10 i.u. oxytocin and 3 received saline i.v. at 08:00 h and blood samples were taken continuously from 10 min before to 60 min after treatment. Mean PGFM response to oestradiol was suppressed (P = 0.05) in CSP- vs plasma protein-treated ewes (371 +/- 129 vs 1188 +/- 139 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
A high-molecular-weight (MW greater than 660,000), acidic glycoprotein (HMWGP) was purified from incubation medium of preimplantation, elongating ovine (day 16 and 17) and porcine (day 16) conceptuses. HMWGP was tested for its ability to inhibit [3H-methyl]thymidine incorporation into lymphocytes stimulated by phytohemagglutinin or two-way mixed lymphocyte cultures. Ovine and porcine HMWGP inhibited the incorporation of [3H-methyl]thymidine into lymphocytes in a dose-dependent manner. An approximately 50% inhibition was detected at the lowest dose tested (ovine, 25 micrograms/ml; porcine, 5 micrograms/ml). Complete suppression of thymidine incorporation occurred at the highest doses evaluated (ovine, 200 micrograms/ml; porcine, 40 micrograms/ml). This immunosuppressive effect was not the result of an overall cytotoxic effect on lymphocytes as evaluated by trypan blue exclusion. In conclusion, an ovine and porcine conceptus glycoprotein, HMWGP, has potent in vitro immunosuppressive activity in both phytohemagglutinin and mixed lymphocyte cultures. In vivo, HMWGP may have an immunoregulatory role during early pregnancy in the sheep and pig by providing a local immunosuppressive environment within the uterus to prevent conceptus rejection.
Interactions of the conceptus with the immune system can involve either anti-sperm or anti-conceptus immune responses that limit the success of pregnancy or beneficial effects of cytokines released from lymphoid cells on embryonic growth and gene expression. The immune system is functional in the uterus and therefore there is the potential for anti-conceptus immune responses. However, endometrial lymphocytes are distinct in many respects from lymphoid cells at peripheral sites; one major subpopulation expresses the 76 T-cell receptor and may not recognize major histocompatibility antigens. There are also several control systems to limit anti-conceptus immune responses. In particular, expression of major histocompatibility antigens on the trophoblast is either absent or of limited distribution. In addition, activation of anti-conceptus immune responses leading to cytolytic responses is further limited by the presence of molecules that can inhibit lymphocyte transformation. The most well-characterized of these are prostaglandin E, from placental and endometrial tissues, interferon-T from the trophoblast during early pregnancy, and two enclometrial proteins called the uterine milk proteins (UTMP). Progesterone plays a central role in inhibition of immune responses in actions that are mediated at least in part through endometrial secretion of UTMP. Cytokines play important roles as autocrine and paracrine regulators in many tissues including the reproductive tract. In ruminants, the best described example is interferon-T. Other cytokines found in the reproductive tract or produced by the conceptus include interleukin-1, leukaemia inhibitory factor, granulocyte-macrophage colony stimulating factor and interleukin-6. It is possible that the major source of cytokines in the reproductive tract is non-lymphoid cells of the endometrium and trophoblast. It is not known to what extent endometrial lymphocytes contribute to the cytokine milieu because no cytokine has been identified as a product of endometrial lymphocytes. However, there is a population of granulated lymphocytes that increase in number and granularity in the luminal epithelium of the late-pregnant ewe that is a potential source of cytokines.
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