Female sexual maturation and reproduction after prepubertal exposure to estrogens and endocrine disrupting chemicals: A review of rodent and human data

Natural hormones and some synthetic chemicals spread into our surrounding environment share the capacity to interact with hormone action and metabolism. Exposure to such compounds can cause a variety of developmental and reproductive detrimental abnormalities in wildlife species and, potentially, in human. Many experimental and epidemiological data have reported that exposure of the developing fetus or neonate to environmentally relevant concentrations of some among these endocrine disrupters induces morphological, biochemical and/or physiological disorders in brain and reproductive organs, by interfering with the hormone actions. The impact of such exposures on the hypothalamic-pituitary-gonadal axis and subsequent sexual maturation is the subject of the present review. We will highlight epidemiological human studies and the effects of early exposure during gestational, perinatal or postnatal life in female rodents. (c) 2006 Elsevier Ireland Ltd. All rights reserved

Interleukin-8 and tumor necrosis factor-α levels in vitreous samples from patients with diabetic retinopathy

AIM: To measure the interleukin-8(IL-8)and tumor necrosis factor-α(TNF-α)levels in vitreous samples obtained the patients undergoing pars plana vitrectomy(PPV)due to diabetic retinopathy(DR), then to compare these results with those of the control group and to state their impact on DR pathogenesis.<p>METHODS: From Istanbul Bilim University Ophthalmology Department, 57 eyes of 57 diabetes mellitus(DM)patients who had been diagnosed with proliferative diabetic retinopathy and 22 cases of macular hole, with no proliferative vitreoretinopathy were included in the study as the study and the control groups respectively. All of the 79 patients underwent a 3-port, 20 gauge PPV. Vitreous samples of 0.5mL were aspirated with vitrector at the beginning of the PPV operation before the intraocular infusion and being diluted. Samples were transferred to the freezer to be stored at -70℃. Results of IL-8 and TNF-α were calculated as pg/mL with ELISA method.<p>RESULTS: IL-8 levels 〖82.7891±74.08700(0.08- 307.09)pg/mL〗 in which vitreous samples obtained DR patients during vitrectomy were significantly elevated when compared to IL-8 levels 〖2.9805±3.77546(0.08-18.53)pg/mL〗 of control patients(<i>P</i><0.001). Similarly, TNF-α level 〖18.0007±13.90015(2.32-51.11)pg/mL〗 was also significantly elevated in DR patients when compared to control patients' TNF-α level 〖1.7005±1.26949(0.1- 5.17)pg/mL〗(<i>P</i><0.001). <p>CONCLUSION: The levels of TNF- α, which plays a role in retinal neovascularization, and, IL-8, which acts as an inflammatory and angiogenic mediator were found to be high in DR patients

Smoothie or Fruit Salad? Learners’ Descriptions of Accents as Windows to Concept Formation

This paper explores the linguistically naive descriptions which one set of EFL learners provided when identifying and describing accents. First and second-year English majors at a French university were asked to do two tasks. First, they listened to two extracts to determine whether the speaker’s accent sounded more British or American, and to explain which features helped them to decide. Later they answered two questions: a) What do you do when you want to sound more like an American? and b) more like a British person? The analysis of their answers highlights learners’ underlying representations of accents as well as concept formation in relation to English pronunciation. I argue that this cognitive aspect of L2 learning should be addressed explicitly in instruction

Nederlands in het perspectief van uitspraakverwerving en contrastieve taalkunde

Nederlands in het perspectief van uitspraakverwerving en contrastieve taalkunde (“Dutch from the point of view of pronunciation acquisition and contrastive linguistics”) gives an overview of linguistic research carried out on Dutch by specialists from different parts of Europe. As the title suggests, the book covers two topics: (1) recent developments in the research into the pronunciation of Dutch as a second or foreign language, including research into pronunciation norms and the teaching of pronunciation; (2) recent theoretical and methodological developments in contrastive linguistics providing new insights about various cross-linguistic issues, including translation

Neurohypophysial Receptor Gene Expression by Thymic T Cell Subsets and Thymic T Cell Lymphoma Cell Lines

Abstract Neurohypophysial oxytocin (OT) and vasopressin (VP) genes are transcribed in thymic epithelium, while immature T lymphocytes express functional neurohypophysial receptors. Neurohypophysial receptors belong to the G protein-linked seven-transmembrane receptor superfamily and are encoded by four distinct genes, OTR, V1R, V2R and V3R. The objective of this study was to identify the nature of neurohypophysial receptor in thymic T cell subsets purified by immunomagnetic selection, as well as in murine thymic lymphoma cell lines RL12-NP and BW5147. OTR is transcribed in all thymic T cell subsets and T cell lines, while V3R transcription is restricted to CD4+ CD8+ and CD8+ thymic cells. Neither V1R nor V2R transcripts are detected in any kind of T cells. The OTR protein was identified by immunocytochemistry on thymocytes freshly isolated from C57BL/6 mice. In murine fetal thymic organ cultures, a specific OTR antagonist does not modify the percentage of T cell subsets, but increases late T cell apoptosis further evidencing the involvement of OT/OTR signaling in the control of T cell proliferation and survival. According to these data, OTR and V3R are differentially expressed during T cell ontogeny. Moreover, the restriction of OTR transcription to T cell lines derived from thymic lymphomas may be important in the context of T cell leukemia pathogenesis and treatment

Effects of early prepubertal exposure to bisphenol A on the onset of puberty, ovarian weights, and estrous cycle in female mice

Objective: Bisphenol A (BPA) is a chemical used extensively to manufacture plastics and epoxy resin liners for food and beverage cans. BPA, with properties similar to estrogen, has endocrine-disrupting effects. In the present study, we examined the effects of early prepubertal BPA exposure on the onset of puberty and reproductive parameters such as estrous cycle and reproductive organ weights in female mice. Methods: Female mice were injected subcutaneously at postnatal day (PND) 8 with BPA (0.1, 1, 10, 100 mg/kg) in sesame oil or with sesame oil alone. Body weight was measured from PND 10 to 70. Vaginal opening and estrous cycle were monitored from PND 20 to 29. Animals were sacrificed at PND 25, 30, and 70, and the ovary and uterus weights were measured. Results: Early prepubertal exposure to BPA (10 and 100 mg/kg) significantly decreased body weight from PND 18 to 30. BPA treated mice at testing dose levels showed early opening of the vagina compared to the control group. The number of estrous cycle and days of estrus were significantly decreased in high dose (100 mg/kg) BPA treated mice. The ovary weight at PND 25 and 30 was significantly decreased in all BPA treatment groups. Conclusion: Early prepubertal exposure to BPA accelerated the onset of puberty but decreased reproductive parameters in female mice

Endocrine disruptors and abnormalities of pubertal development

Onset and development of puberty is regulated by the neuroendocrine system. Population-based studies worldwide have observed secular trends towards earlier puberty development. These changes are apparently caused by environmental factors such as improved socio-economic status, improved health care and nutrition. However, they may also partly result from endocrine-disrupting chemicals in the environment. Epidemiological studies have investigated the relationship between pubertal development and exposure to endocrine-disrupting chemicals (polychlorinated biphenyls, polybrominated biphenyls, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, phthalate esters, furans and the pesticide endosulfan). Associations with both perinatal and postnatal exposure have been reported. Studies in experimental animals support some of these findings and point to differential endocrine regulatory mechanisms linked to pubertal development acting in the perinatal and the pre-pubertal period. Pubertal development is naturally associated with growth and body composition. There is increasing evidence for a link between prenatal development and pubertal onset. In girls born small for gestational age (SGA), pubertal onset and age at menarche often are advanced, especially if there has been an extensive catch-up growth during the first months of life. In utero growth retardation may have multiple causes including exposure to xenobiotic substances as was suggested for some endocrine-disrupting chemicals. An abnormal perinatal environment of children born SGA may alter the endocrine status and the sensitivity of the receptors for endocrine and metabolic signalling that may have effects on maturation of brain and gonads. However, the causal pathways and the molecular mechanisms that may link the pubertal growth pattern of children born SGA, pubertal development and endocrine-disrupting chemicals need further study

Exposure to p,p′-DDE: A Risk Factor for Type 2 Diabetes

BACKGROUND: Persistent organic pollutants (POPs), such as PCBs, DDT and dioxins have in several cross-sectional studies shown strong associations with type 2 diabetes mellitus. Reversed causality can however not be excluded. The aim of this case-control study was to evaluate whether POPs concentration is a risk factor for type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: A case-control study was performed within a well-defined cohort of women, age 50-59 years, from the Southern part of Sweden. Biomarkers for POP exposure, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) were analyzed in stored serum samples, which were collected at the baseline examination when the cohort was established. For 107 out of the 371 cases, serum samples were stored at least three years before their type 2 diabetes was diagnosed. In this data set, CB-153 and p,p'-DDE were not associated with an increased risk to develop type 2 diabetes. However, when only the cases (n = 39) that were diagnosed more than six years after the baseline examination and their controls were studied, the women in the highest exposed quartile showed an increased risk to develop type 2 diabetes (OR of 1.6 [95% 0.61, 4.0] for CB-153 and 5.5 [95% CI 1.2, 25] for p,p'-DDE). CONCLUSIONS/SIGNIFICANCE: The results from the present case-control study, including a follow-up design, confirms that p,p'-DDE exposure can be a risk factor for type 2 diabetes

Interleukin and Growth Factor Levels in Subretinal Fluid in Rhegmatogenous Retinal Detachment: A Case-Control Study

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a major cause of visual loss in developed countries. Proliferative vitreoretinopathy (PVR), an eye-sight threatening complication of RRD surgery, resembles a wound-healing process with inflammation, scar tissue formation, and membrane contraction. This study was performed to determine the possible involvement of a wide range of cytokines in the future development of PVR, and to identify predictors of PVR and visual outcome. METHODOLOGY: A multiplex immunoassay was used for the simultaneous detection of 29 different cytokines in subretinal fluid samples from patients with primary RRD. Of 306 samples that were collected and stored in our BioBank between 2001 and 2008, 21 samples from patients who developed postoperative PVR were compared with 54 age-, sex-, and storage-time-matched RRD control patients who had an uncomplicated postoperative course during the overall follow-up period. FINDINGS: Levels of IL-1α, IL-2, IL-3, IL-6, VEGF, and ICAM-1 were significantly higher (P<0.05) in patients who developed postoperative PVR after reattachment surgery than in patients with an uncomplicated postoperative course, whereas levels of IL-1β, IL-4, IL-5, IL-7, IL-9, IL-10, IL-11, IL-12p70, IL-13, IL-15, IL-17, IL-18, IL-21, IL-22, IL-23, IL-25, IL-33, TNF-α, IFN-γ, IGF-1, bFGF, HGF, and NGF were not (P>0.05). Multivariate logistic regression analysis revealed that IL-3 (P = 0.001), IL-6 (P = 0.047), ICAM-1 (P = 0.010), and preoperative visual acuity (P = 0.026) were independent predictors of postoperative PVR. Linear regression analysis showed that ICAM-1 (P = 0.005) and preoperative logMAR visual acuity (P = 0.001) were predictive of final visual outcome after primary RRD repair. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that after RRD onset an exaggerated response of certain cytokines may predispose to PVR. Sampling at a time close to the onset of primary RRD may thus provide clues as to which biological events may initiate the development of PVR and, most importantly, may provide a means for therapeutic control