Endocrine control of mucosal immunity in the female reproductive tract: impact of environmental disruptors

The complexity of the human female reproductive tract (FRT) with its multiple levels of hormonally controlled immune protection has only begun to be understood. Dissecting the functions and roles of the immune system in the FRT is complicated by the differential hormonal regulation of its distinct anatomical structures that vary throughout the menstrual cycle. Although many fundamental mechanisms of steroid regulation of reproductive tract immune function have been determined, the effects of exogenous synthetic steroids or endocrine disruptors on immune function and disease susceptibility in the FRT have yet to be evaluated in detail. There is increasing evidence that environmental or synthetic molecules can alter normal immune function. This review provides an overview of the innate and adaptive immune systems, the current status of immune function in the FRT and the potential risks of environmental or pharmacological molecules that may perturb this system.     

Angiogenesis in reproductive tissues

Angiogenesis is the process of generating new capillaries and leads, therefore, to vascularization of tissues. This process occurs during embryological development and during pathological and physiological conditions in adult life, including those involving the reproductive organs. Recent studies, in the field of tumour biology in particular, have led to the identification of several factors responsible for inducing angiogenesis and the elucidation of ways of modulating their activity. This review summarizes our knowledge of angiogenesis in the ovary, testis, endometrium and placenta, and suggests ways in which further research might contribute to a better understanding of the processes controlling reproduction and identify new approaches to the regulation of fertility.     

O139霍乱弧菌肠毒素核苷酸序列分析

目的 探讨Ｏ１３９霍乱弧菌肠毒素（ＣＴＸ）核苷酸与Ｏ１群霍乱ＣＴＸ毒素核苷酸序列异同。方法 用聚合酶链反应、ＤＮＡ序列分析测定２株Ｏ１３９群、２株Ｏ１群古典型、２株Ｏ１群Ｅ１Ｔｏｒ型霍乱弧菌ＣＴＸＡ２－Ｂ亚单位核苷酸。结果 ２株Ｏ１３９群霍乱弧菌均含有ＣＴＸＡ２－Ｂ亚单位基因,Ｏ１３９群与Ｏ１群ＣＴＸＡ２－Ｂ核苷酸同源性为９７．１％～９８．９％结论 Ｏ１３９群与Ｏ１群霍乱弧菌ＣＴＸ核苷酸序列一致。     

The study of intestinal immunity against V. cholerae: purification of V. cholerae El Tor haemagglutinin and the protective role of its antibody in experimental cholera.

V. cholerae El Tor Ogawa strain O17SR grown on trypticase soy agar were extracted with 0.05 M cyclohexylamino propane sulfonic acid (CAPS) pH 9.5 at 37 degrees C for 1 hour. The bacteria were then removed by centrifugation and millipore filtration. The filtered fluid, after being dialysed against many changes of cold distilled water, was concentrated and passed through Sephadex G200 column. Three protein profiles were eluted out with 0.05 M Tris buffer pH 8.6. The haemagglutinin and the bacterial lipopolysaccharide (LPS) were confined to the first profile. They were subsequently separated by agarose gel electrophoresis. The haemagglutinin was found to be more anodic than the LPS. After homogenization of the gel strips containing the haemagglutinin followed by centrifugation at 9,000 g pure haemagglutinin was obtained in the supernatant. Rabbit aniserum against pure haemagglutinin contained protective antibodies against V. cholerae infection in the baby mouse model. Specific antibodies prepared from this antiserum was as protective as the antibodies directed against whole V. cholerae and heat stable somatic antigens of V. cholerae upon the same weight unit.     

Relaxin in the pregnant baboon: evidence for local production in reproductive tissues

We examined the nonluteal production of relaxin in the pregnant baboon. In experimental animals (n = 5), the corpus luteum-bearing ovary was removed in early pregnancy (days 25-30), and intact pregnant baboons served as controls. In both groups of baboons, peripheral, uterine, and ovarian venous blood samples and amniotic fluid were collected immediately before hysterotomy, which was performed late in pregnancy (days 139-142). After hysterotomy, samples of reproductive and control tissues were obtained (placenta, decidua, myometrium, fetal membranes, and omentum). Relaxin concentrations were determined in all samples using an antiporcine relaxin RIA. In unilaterally oophorectomized pregnant baboons, peripheral plasma levels of relaxin were below the limits of detection (less than 157 pg/ml) for 100 days following corpus luteum removal, while levels in control pregnant baboons were greater than 1000 pg/ml. Relaxin levels in uterine venous plasma were comparable to peripheral plasma levels in each group. Relaxin concentrations in amniotic fluid of both groups were below the limits of detection (less than 157 pg/ml). Relaxin was found in decidua, placenta, and myometrium in those pregnant baboons in which the corpus luteum-bearing ovary had been removed over 100 days earlier. This finding together with the absence of a relaxin gradient in uterine venous plasma and undetectable relaxin levels in amniotic fluid is a strong indication of local relaxin production in reproductive tissues without contribution to peripheral plasma levels.     

Relaxin signaling in reproductive tissues

The insulin/relaxin peptide family includes insulin, IGFs, relaxin1-3, INSL3/RLF, INSL4, INSL5/RIF2 and INSL6/RIF1, many without functional characterization. Based on analysis of transgenic phenotypes and phylogenetic profiling, we have discovered that two orphan leucine-rich repeat-containing G protein-coupled receptors, LGR7 and LGR8, are cognate receptors for relaxin whereas INSL3 is a specific ligand for LGR8. With the identification of the relaxin receptors, it is now possible to investigate specific cells and tissues that are responsive to relaxin in diverse physiological and pathological conditions as well as to develop agonists and antagonists for LGR7 and LGR8 as therapeutics to treat different labor disorders. Furthermore, future functional characterization of the specificity of these pluripoentent receptors with peptide ligands could lead to the understanding of related orphan ligands and receptors.     

霍乱毒素作为黏膜佐剂的研究进展

霍乱毒素(cholera toxin,CT)是霍乱弧菌分泌的一种不耐热肠毒素,既是强黏膜免疫原,又具有很强的黏膜佐剂活性,是当今研究最多且最深入的黏膜免疫佐剂之一。然而,由于CT其毒性,限制了在人体的使用。很多研究致力于使CT的佐剂性与毒性分离,CT亚基的佐剂性的研究就是方向之一。困扰黏膜疫苗的一个重要问题是很多抗原的黏膜免疫原性较弱,不能刺激有效的免疫反应,这也与黏膜免疫耐受有关,以CT为佐剂能消除机体对这些共免疫原的耐受。     

Current status of cholera and rise of novel mucosal vaccine

Three serious cholera epidemics have threatened the world during the last 10 years. As a countermeasure against such cholera epidemics, three vaccines, CVD 103-HgR, WC/rBS, and Vietnamese WC, showed good performance. CVD 103-HgR is a recombinant attenuated live vaccine for travelers, and its highly safety and protective efficacy have been demonstrated in volunteers in advanced countries. WC/rBS, which consists of heat- and formalin-killed bacteria and cholera toxin B subunit, protects the vaccinees (>5 years old) from cholera for 6 months. Vietnamese WC, a heat- and formalin-killed vaccine, is inexpensive and effective even for 1 to 5-year-old children. Additionally, irradiated WC vaccines and new serotype (O139) vaccines are being developed. Regarding intestinal immunity, secretory IgA has been mainly examined. In addition, mucosal IgG, as induced by the irradiated WC vaccine, should also be investigated. Development of mucosal adjuvant, such as holotoxin-type mutants of cholera toxin and related Escherichia coli heat-labile enterotoxin, has been actively undertaken. Diverse custom-made vaccines may be one countermeasure for the changing situations in endemic countries or areas and for "barriers" against live vaccines in such areas.     

Local environmental predictors of cholera in Bangladesh and Vietnam

Environmental factors have been shown to be related to cholera and thus might prove useful for prediction. In Bangladesh and Vietnam, temporal cholera distributions are related to satellite-derived and in-situ environmental time series data in order to examine the relationships between cholera and the local environment. Ordered probit models examine associations in Bangladesh; probit models examine associations at 2 sites in Vietnam. Increases in ocean chlorophyll concentration are related to an increased magnitude of cholera in Bangladesh. Increases in sea surface temperature are most influential in Hue, Vietnam, whereas increases in river height have a significant role in Nha Trang, Vietnam. Cholera appearance and epidemic magnitude are related to the local environment. Local environmental parameters have consistent effects when cholera is regular and more prevalent in endemic settings, but in situations where cholera epidemics are rare there are differential environmental effects.