Publications by authors named "Brian Setchell"

Objective: To determine whether dietary and exercise regimes in obese males can provide a novel intervention window for improving the reproductive health of the next generation.

Design: Experimental animal study.

Setting: University research facilities.

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Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established.

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Male obesity is associated with reduced sperm motility and morphology and increased sperm DNA damage and oxidative stress; however, the reversibility of these phenotypes has never been studied. Therefore, the aim of this study was to assess the reversibility of obesity and its associated sperm physiology and function in mice in response to weight loss through diet and exercise. C57BL6 male mice (n = 40) were fed either a control diet (CD; 6% fat) or a high-fat diet (HFD; 21% fat) for 10 wk before allocation to either diet and/or swimming exercise interventions for 8 wk.

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Male obesity is associated with reduced sperm function and increased incidence of sperm DNA damage; however, the underlying molecular mechanisms have not yet been identified. Mammalian SIRT6 protein is involved in caloric-dependant DNA damage repair in other tissue types, yet a possible role for SIRT6 in male obesity and subfertility has not been investigated previously. To assess SIRT6 levels and activity in the testes, male mice (n=12 per diet) were fed either a control diet (CD; 6% fat) or a high-fat diet (HFD; 21% fat) for 16 weeks before the collection of testes and spermatozoa.

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This study was carried out to determine if exposure to hot environmental temperatures had a direct, detrimental effect on sperm quality. For this the effect of whole-body heat exposure on epididymal spermatozoa of laboratory mice was investigated. C57BL/6 mice (n = 7) were housed in a microclimate chamber at 37 degrees C-38 degrees C for 8 h per day for three consecutive days, while control mice (n = 7) were kept at 23 degrees C-24 degrees C.

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The Leydig cell-specific factor insulin-like peptide 3 (INSL3) is involved in testicular descent during embryo development, and has been suggested to regulate spermatogenesis and bone metabolism in the adult. Using a new, sensitive assay specific for rodent INSL3, we have mapped the secretion of INSL3 into peripheral blood in mice and during postnatal male rat development (in female rats, circulating INSL3 is at the level of detection). Maximum INSL3 is measured at Postnatal Day (PD) 40 in the rat and decreases to a significantly lower, stable value by PD60, indicating an "overshoot" effect in the establishment of Leydig cell functionality during the first wave of spermatogenesis.

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Although host-defence mechanisms, designed to preserve the integrity of the developing germ cells are operative in the testis, the components of this protective system have yet to be characterised in detail. Here, we report that the cytokine interleukin-18 (IL-18) is expressed in the rat testis and may contribute to these defences. Thus, analysis by RT-PCR and Western blotting revealed pronounced testicular expression of pro-IL-18 from postnatal day 5 and onwards.

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Pregnant ewes with catheters implanted in an artery and the uterine and recurrent tarsal veins were infused at a constant rate with U-(14)C-labelled glucose, alanine or bicarbonate. Measurements were made of the overall and local fractional contribution of glucose and alanine to CO(2) production and of the extent of interconversion of these metabolites. In the whole animal, by coupling the results with the authors' previous study of lactate metabolism, a solution was obtained to an open unrestricted 4-compartment model of the exchange of carbon between glucose, lactate, alanine and CO(2).

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hCG has been reported to cause an inflammation-like effect in the testis, although the background and consequences of this phenomenon remain to be understood. This investigation reveals that a single injection of hCG (100 U) induces a transient surge in pro-inflammatory cytokine expression in the adult rat testis. Reverse transcriptase PCR analysis demonstrated onset of testicular expression of IL-1beta and IL-6 mRNA and increases in the levels of mRNA encoding the constitutively expressed cytokines IL-1alpha, IL-1 receptor antagonist, and tumor necrosis factor-alpha 4 h after hCG injection and a maximal response after 8-12 h.

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The present study characterizes constitutively expressed rat testicular interleukin-1alpha (IL-1alpha) proteins. IL-1 bioactivity of crude testis protein was completely neutralized by IL-1alpha antiserum, IL-1 receptor antagonist, and soluble type I IL-1 receptor. Upon non-denaturating gel permeation chromatography, bioactive IL-1 eluted at molecular sizes of 45, 31, and 17kDa and at charges of pH 5.

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