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Liu Y.,Shanghai JiaoTong University | Zhao W.,Yunnan University | Lu L.,Shanghai Institute of Immunology | Feng J.,Shanghai JiaoTong University | And 2 more authors.
Molecular Reproduction and Development | Year: 2014

Male obesity may lead to declines in testosterone levels, reproductive hormonal profile, and semen quantity. To assess the effects of obesity on spermatogenesis, Sprague-Dawley rats fed a high-fat diet served as a model of induced obesity. The litter sizes for females mated to obese males were significantly lower as compared to females mated with normal-diet-fed controls. Their serum high-density lipoprotein, low-density lipoprotein, cholesterol, and estradiol levels increased in obese males, but testosterone and follicle-stimulating hormone levels decreased. Testicular morphology disruptions included Sertoli-cell atrophy, disrupted tight junctions, and mitochondrial degeneration in spermatogenic cells. To further investigate the molecular mechanisms leading to high-fat-diet-induced changes, we employed testicular proteomic analysis on rats fed both types of diet. Three spots were up-regulated in rats fed a high-fat diet whereas two others were downregulated. One of the upregulated spots was palmitoyl-protein thioesterase 1 (PPT1), a lipoprotein metabolizing related enzyme localized to Sertoli cells. In a Sertoli-cell line cultured in a high-fat supplemented medium, PPT1 abundance was accompanied by increases in the endocytic vesicle-associated protein, clathrin, and decreases in the tight junctional proteins, ZO-1 and occludin. In conclusion, declines in rat male fertility induced by a high-fat diet are associated with an altered testicular protein expression pattern as well as disruption of testicular Sertoli-cell and spermatogenic-cell morphology. PPT1 expression may provide a testicular marker of reduced fertility in obese males, as increases in its expression may be detrimental to Sertoli-cell function during spermatogenesis. © 2013 Wiley Periodicals, Inc. Source

Liu W.,Shanghai JiaoTong University | Wang S.-J.,Shanghai Institute of Immunology | Lin Q.-D.,Shanghai JiaoTong University
International Journal of Biological Sciences | Year: 2014

Objective: To investigate the relationship between oxygen sensitivity of trophoblast and hypoxia in preeclamptic placenta by the study on the expressions of hypoxia-inducible factor prolyl 4-hydroxylase (PHD) and hypoxia-inducible factor (HIF) in placentas from normal pregnant women and patients with pre-eclampsia. Methods: Subjects were chosen from the in-patients or the out-patients from May 2003 to May 2004. They were divided into 5 groups: early pregnancy group (EP), 13 cases; middle pregnancy group (MP), 9 cases; late pregnancy group (LP, or control group), 12 cases; preeclampsia (PE) group, 20 cases; gestational hypertension group (GH), 10 cases. The mRNA expressions of PHD-1 and -2 and -3 in placentas from all the subjects were assessed by in situ hybridization and Real- time PCR. The expressions of HIF-1α and -2α in placentas from different groups were assessed by immunohistochemistry and western blot. Results: PHD-1,-2 and -3 mRNA were mainly expressed in cytoplasm of trophoblast, especially strongly expressed in extravillous trophoblast. During the progress of pregnancy, the expression of PHD-1 increased significantly (R=0.616, P<0.001). The PHD-1mRNA expression in placentas from PE group decreased significantly compared with that from control group, P<0.05. A significant direct correlation between the PHD-1 mRNA expression in placentas from PE group and their placenta weight was found (R=0.457, P<0.05). The HIF-2α, not the HIF-1α expression, from PE group was significantly higher than that from control group, P<0.01; The HIF-2α expression in trophoblast from PE was inversely correlated to the date of the onset of the disease (R=-0.730, P<0.01). Conclusions: PHD-1 played an important role in hypoxic response pathway of trophoblast through modulating the level of HIF-2α. The overly activated hypoxic response pathway of trophoblast in preeclamptic placenta, which is manifested as the result of HIF-2α over-expression, is the key point to hypoxic dysfunction of trophoblast. © Ivyspring International Publisher. Source

Liu Y.,Shanghai JiaoTong University | Qu F.,Shanghai JiaoTong University | Cao X.,Shanghai Jiai Genetics and Institute China United States Center | Chen G.,Shanghai Jiai Genetics and Institute China United States Center | And 5 more authors.
International Journal of Andrology | Year: 2012

Fertilization, the recognition and fusion between spermatozoa and oocyte, involves various molecules on the spermatozoa and oocyte membranes. Concanavalin A (ConA)-binding proteins may be one of the molecules involved in mammal spermatozoa fertilization; however, their structure and function remain largely unknown. Here, we initially identified a ConA-binding protein, Zn-α2-glycoprotein (ZAG), involved in regulating the acrosome reaction (AR) of human spermatozoa. ZAG is localized on the pre-equatorial region covering the acrosome, neck and tail (some parts of middle piece and principal piece respectively) regions of the acrosome intact human spermatozoa, and disappears in the acrosomal region of the acrosome-reacted spermatozoa. Polyclonal antibodies against human recombinant ZAG significantly reduced the AR and sperm capability binding to human zona pellucida or penetration into zona-free hamster oocytes. Furthermore, assessment of the signaling pathways regulated by ZAG revealed that ZAG affects sperm AR through both the cAMP/PKA and PKC pathways. These results indicate that ZAG, which is present on the human sperm membrane, plays a critical role in the AR and subsequently, may be involved in sperm fertility. © 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology. Source

Zhou A.,Shanghai JiaoTong University | Ni J.,Shanghai JiaoTong University | Xu Z.,Shanghai JiaoTong University | Wang Y.,Shanghai Institute of Immunology | And 4 more authors.
Journal of Proteome Research | Year: 2013

Nuclear magnetic resonance (NMR) spectroscopy is an ideal platform for the metabolic analysis of biofluids due to its high reproducibility, nondestructiveness, nonselectivity in metabolite detection, and the ability to simultaneously quantify multiple classes of metabolites. Tuberculosis (TB) is a chronic wasting inflammatory disease characterized by multisystem involvement, which can cause metabolic derangements in afflicted patients. In this study, we combined multivariate pattern recognition (PR) analytical techniques with 1H NMR spectroscopy to explore the metabolic profile of sera from TB patients. A total of 77 serum samples obtained from patients with TB (n = 38) and healthy controls (n = 39) were investigated. Orthogonal partial least-squares discriminant analysis (OPLS-DA) was capable of distinguishing TB patients from controls and establishing a TB-specific metabolite profile. A total of 17 metabolites differed significantly in concentration between the two groups. Serum samples from TB patients were characterized by increased concentrations of 1-methylhistidine, acetoacetate, acetone, glutamate, glutamine, isoleucine, lactate, lysine, nicotinate, phenylalanine, pyruvate, and tyrosine, accompanied by reduced concentrations of alanine, formate, glycine, glycerolphosphocholine, and low-density lipoproteins relative to control subjects. Our study reveals the metabolic profile of sera from TB patients and indicates that NMR-based methods can distinguish TB patients from healthy controls. NMR-based metabolomics has the potential to be developed into a novel clinical tool for TB diagnosis or therapeutic monitoring and could contribute to an improved understanding of disease mechanisms. © 2013 American Chemical Society. Source

Zhou A.,Tongji University | Zhou A.,Shanghai JiaoTong University | Zhou A.,Tibet University | Ni J.,Shanghai JiaoTong University | And 8 more authors.
Tuberculosis | Year: 2015

Tuberculosis (TB) is a communicable disease of major global importance and causes metabolic disorder of the patients. In a previous study, we found that the plasma metabolite profile of TB patients differs from that of healthy control subjects based on nuclear magnetic resonance (NMR) spectroscopy. In order to evaluate the TB specificity of the metabolite profile, a total of 110 patients, including 40 with diabetes, 40 with malignancy, and 30 with community-acquired pneumonia (CAP), assessed by NMR spectroscopy, and compared to those of patients with TB. Based on the orthogonal partial least-squares discriminant analysis (OPLS-DA), the metabolic profiles of these diseases were significant different, as compared to the healthy controls and TB patients, respectively. The score plots of the OPLS-DA model demonstrated that TB was easily distinguishable from diabetes, CAP and malignancy. Plasma levels of ketone bodies, lactate, and pyruvate were increased in TB patient compared to healthy control, but lower than CAP and malignancy. We conclude that the metabolic profiles were TB-specific and reflected MTB infection. Our results strongly support the NMR spectroscopy-based metabolomics could contribute to an improved understanding of disease mechanisms and may offer clues to new TB clinic diagnosis and therapies. © 2015 Elsevier Ltd. Source

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