93 research outputs found
Interleukin-18 is expressed in rat testis and may promote germ cell growth
No full textMona-Lisa Strand, Aida Wahlgren, Konstantin Svechnikov, Cecilia Zetterstroma, Brian P. Setchell, Olle Sode
Single subcutaneous administration of chorionic gonadotropin to rats induces a rapid and transient increase in testicular expression of pro-inflammatory cytokines
No full textMonique Assmus, Konstantin Svechnikov, Mikael Von Euler, Brian Setchell, Taranum Sultana, Cecilia Zetterström, Mikael Holst, Wieland Kiess and Olle Söde
Improving metabolic health in obese male mice via diet and exercise restores embryo development and fetal growth
No full textPaternal 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. Here, male mice fed a high fat diet (HFD) to induce obesity were used, to determine if early embryo and fetal development is improved by interventions of diet (CD) and/or exercise to reduce adiposity and improve metabolism. Exercise and to a lesser extent CD in obese males improved embryo development rates, with increased cell to cell contacts in the compacting embryo measured by E-cadherin in exercise interventions and subsequently, increased blastocyst trophectoderm (TE), inner cell mass (ICM) and epiblast cell numbers. Implantation rates and fetal development from resulting blastocysts were also improved by exercise in obese males. Additionally, all interventions to obese males increased fetal weight, with CD alone and exercise alone, also increasing fetal crown-rump length. Measures of embryo and fetal development correlated with paternal measures of glycaemia, insulin action and serum lipids regardless of paternal adiposity or intervention, suggesting a link between paternal metabolic health and subsequent embryo and fetal development. This is the first study to show that improvements to metabolic health of obese males through diet and exercise can improve embryo and fetal development, suggesting such interventions are likely to improve offspring health.Nicole O. McPherson, Hassan W. Bakos, Julie A. Owens, Brian P. Setchell, Michelle Lan
Tandem Mass Spectrometric Determination of Atypical 3-Hydroxy-Δ5-Bile Acids in Patients with 3-Hydroxy-Δ5-C27-Steroid Oxidoreductase Deficiency: Application to Diagnosis and Monitoring of Bile Acid Therapeutic Response
No full text3Beta-hydroxy-5-C27-steroid oxidoreductase (HSD3B7) deficiency, a progressive cholestatic liver disease, is the most common genetic defect in bile acid synthesis. Early diagnosis is important because patients respond to oral primary bile acid therapy, which targets the negative feedback regulation for bile acid synthesis to reduce the production of hepatotoxic 3beta-hydroxy-5-bile acids. These atypical bile acids are highly labile and difficult to accurately measure, yet a method for accurate determination of 3-hydroxy-5-bile acid sulfates is critical for dose titration and monitoring response to therapy
SIRT6 in mouse spermatogenesis is modulated by diet-induced obesity
No full textMale 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. SIRT6 protein was localised to the nucleus of transitional spermatids and the acrosome of mature spermatozoa, with levels significantly decreased in HFD-fed male mice (P < 0.05). This decrease in SIRT6 protein was associated with transitional spermatids having increased levels of acetylated H3K9 in the nucleus (P < 0.01) and increased DNA damage (P < 0.001). We propose a role for SIRT6 in spermiogenesis and potentially protamination processes, which are known to be compromised by male obesity.Nicole O. Palmer, Tod Fullston, Megan Mitchell, Brian P. Setchell and Michelle Lan
Fluid exchange and transport of hydrophilic factors in the testis
No full textBrian Peter Setchellhttp://www.springer.com/humana+press/book/978-1-58829-754-
Whole-body heat exposure induces membrane changes in spermatozoa from the cauda epididymidis of laboratory mice
No full textThis 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 37ºC–38ºC for 8 h per day for three consecutive days, while control mice (n = 7) were kept at 23ºC–24ºC. Cauda epididymal spermatozoa were obtained 16 h after the last heat treatment. The results showed that sperm numbers were similar in the two groups (P = 0.23), but after heat treatment, a significant reduction in the percentage of motile sperm was present (P < 0.0001). Membrane changes of the spermatozoa were investigated by staining with phycoerythrin (PE)- conjugated Annexin V, which detects exteriorization of phosphotidylserine from the inner to the outer leaflet of the sperm plasma membrane, and 7-aminoactinomycin D (7-AAD), which binds to the sperm nucleus when the plasma membrane is damaged. The percentage of spermatozoa showing positive staining with Annexin V–PE or 7-AAD or both, was significantly higher (P < 0.05) in heat-exposed mice compared with controls. These results show that whole-body heat exposure to 37ºC–38ºC induces membrane changes in the epididymal spermatozoa of mice, which may lead to apoptosis.Harsha Wechalekar, Brian P. Setchell, Eleanor J. Peirce, Mario Ricci, Chris Leigh and William G. Bree
Secretion of D-aspartic acid by the rat testis and its role in endocrinology of the testis and spermatogenesis
No full textAbstractThe D-isomer of aspartic acid (D-Asp) has been found in rat testes. In the present study, samples of testicular venous blood plasma, rete testis fluid, interstitial extracellular fluid, luminal fluid from the seminiferous tubules, testicular parenchymal cells, epididymal spermatozoa and peripheral blood plasma were collected and analyzed for D-Asp by two methods, an enzymatic and a chromatographic HPLC method. The two methods gave very similar results for all samples. The highest concentrations of D-Asp (about 120 nmol/ml) were found in testicular venous blood plasma, with slightly lower concentrations in rete testis fluid (95 nmol/ml) and epididymal spermatozoa (80 nmol/g wet weight). Lower levels were found in testicular parenchymal cells (which would comprise mostly spermatids and spermatocytes), luminal fluid from the seminiferous tubules and interstitial extracellular fluid (26, 23 and 11 nmol/ml respectively). However, these values were all higher than those for peripheral blood plasma (6 nmol/ml). It would appear that D-Asp is being secreted by the testis mostly into the venous blood, passing thence into the rete testis fluid and being incorporated into the spermatozoa at the time or after they leave the testis. The distribution of D-Asp is thus quite different from that of testosterone, and its role and the reason for its high concentration in the male reproductive tract remain to be elucidated
The recycling of carbon in glucose, lactate and alanine in sheep
No full textPregnant ewes with catheters implanted in an artery and the uterine and recurrent tarsal veins were infused at a constant rate with U−¹⁴C-labelled glucose, alanine or bicarbonate. Measurements were made of the overall and local fractional contribution of glucose and alanine to CO₂ 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 CO₂. A more limited study was made with non-pregnant sheep because complete data for lactate interactions with alanine were not available. Our analysis of glucose/lactate/alanine/CO₂ interactions in pregnant sheep suggests that about two-thirds of the glycogenic carbon was oxidised fairly directly to CO₂. There was relatively little recycling of glucose carbon through lactate and alanine so that most of the remaining glycogenic carbon was stored as product with relatively long turnover time. It is possible that much of this was in the form of muscle glycogen, and analysis of glycogenic carbon exchange across the hind limb muscle was consistent with this conclusion. In non-pregnant ewes, the findings, although incomplete, suggested that there were no great differences from the findings in pregnant ewes.Derek B. Lindsay, Patrick J. Barker, Andrew J. Northrop, Brian P. Setchell, Graham J. Faichne
- …
