| 1. |
- Andreucci, Alessandro, et al.
(author)
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Cadmium may impair prostate function as measured by Prostate Specific Antigen in semen: a cross-sectional study among European and Inuit men.
- 2015
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In: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 53:Feb 3, s. 33-38
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Journal article (peer-reviewed)abstract
- We investigated the association between cadmium in blood and the concentration of the prostate specific antigen (PSA) in semen, including the modifying effects of zinc or the CAG polymorphism in the androgen receptor (AR). Blood and semen samples were collected from 504 partners of pregnant women in Greenland, Poland and Ukraine. We found an inverse trend between cadmium and PSA (log (ß)= -0.121, 95% Confidence Interval (CI):-0.213; -0.029, P=0.0103) in Greenlandic men. Similar results were observed in men with a high number of CAG repeats (CAG 24) (log (ß)=-0.231, 95% CI:-0.363; -0.098, P=0.0009). Inverse trends between cadmium and PSA were found when semen zinc concentrations were below the median value for men from Ukraine and Greenland. These outcomes suggest that cadmium may impair prostate function, as measured by PSA in semen, while high zinc levels and a low number of CAG repeats protects against this action.
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| 2. |
- Christensen, P S, et al.
(author)
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Environmental cadmium and lead exposure and anti-Müllerian hormone in pregnant women
- 2016
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In: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 61, s. 114-119
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Journal article (peer-reviewed)abstract
- BACKGROUND: Anti-Müllerian Hormone (AMH) has been suggested as a marker for ovarian function. Cadmium and lead have been suggested to reduce female fecundity. In this study we aimed to investigate whether environmental exposure to cadmium and lead was associated with alterations in serum-AMH.MATERIALS AND METHOD: The associations between serum-AMH and whole blood cadmium or lead were investigated by general linear models in a population-based sample of 117 pregnant women.RESULTS: The mean concentrations of blood cadmium and lead were 0.71μg/L and 17.4μg/L, respectively. The mean serum-AMH was 17.3pmol/L. No association between lead and AMH was detected. In the cadmium analysis the adjusted mean AMH level (95% CI) in the highest exposure tertile was 12.4 (6.4;23.8) compared to 5.6 (2.7;11.4) in the lowest exposure tertile (p=0.06).CONCLUSION: The study provides suggestive evidence that environmental exposure to cadmium, but not lead, may alter the level of AMH.
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| 7. |
- Ejdesjö, Andreas, 1978-, et al.
(author)
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Receptor for Advanced Glycation End products (RAGE) knockout reduces fetal dysmorphogenesis in murine diabetic pregnancy
- 2016
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 62, s. 62-70
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Journal article (other academic/artistic)abstract
- Background & Aim: The receptor for Advanced Glycation End products (RAGE) is implicated in the pathogenesis of diabetic complications, but its importance for the induction of congenital malformations in diabetic pregnancy is unclear. The aim of the present study was to investigate a possible role of RAGE activation in the induction of diabetic embryopathy.Methods: Female non-diabetic and diabetic wildtype (WT) C57Bl/6 mice and RAGE knockout C57Bl/6 (RAGE‑/-) mice were mated with males of the same genotype. Diabetes was induced by daily streptozotocin (STZ) injections (50 mg/kg STZ i.p.) on five consecutive days. On gestational day 18, pregnant mice were anesthetized and blood was drawn from the heart to measure maternal metabolic parameters. Fetuses and placentas were excised, weighed, and examined for morphological anomalies, and fetal livers were analyzed for 8‑iso‑PGF2α levels.Results: There were no malformations in non-diabetic WT or non-diabetic RAGE‑/- mice. However, resorption rates were higher in non-diabetic WT (10%) than in non-diabetic RAGE‑/- mice (4%). Diabetic WT mice had higher malformation (22%) and resorption (43%) rates than diabetic RAGE‑/- mice (3% malformations and 21% resorptions). Maternal diabetes decreased fetal weight more in WT fetuses (44%) than in RAGE‑/- fetuses (36%). There were no differences in plasma glucose levels between the diabetic WT and RAGE‑/- mice, but plasma levels of triglycerides and cholesterol were lower in diabetic WT mice than in diabetic RAGE-/- mice. Diabetes increased maternal plasma levels of methylglyoxal in WT and RAGE‑/- mice, and increased fetal hepatic levels of 8-iso-PGF2α in WT fetuses, but not in RAGE‑/- fetuses. Discussion: Knockout of RAGE diminished the rates of fetal malformations and resorptions, despite similar levels of hyperglycemia in pregnant diabetic mice. An anti-teratogenic effect was present in RAGE‑/- mice despite having a more severe diabetic state than diabetic WT mice. As 8-iso-PGF2α, a marker of oxidative stress, only increased in diabetic WT offspring, this suggested a pivotal role of RAGE activation and oxidative stress in the pathogenesis of diabetic embryopathy.
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| 8. |
- Hallberg, Ida, et al.
(author)
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Perfluorononanoic acid (PFNA) alters lipid accumulation in bovine blastocysts after oocyte exposure during in vitro maturation
- 2019
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 84, s. 1-8
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Journal article (peer-reviewed)abstract
- Perfluorononanoic acid (PFNA) is one of the perfluoroalkyl acids present in human tissues. In this study, effects on early embryo development after PFNA exposure were investigated using the bovine in vitro production system. Oocytes were exposed to PFNA during maturation in vitro (10 μg mL-1 and 0.1 μg mL-1), and then fertilized and cultured in parallel with control groups. Developmental parameters (cleavage, blastocyst formation) were followed and embryo quality evaluated (stage, grade). Embryos developed after exposure to 0.1 μg mL-1 were stained to distinguish nuclei, active mitochondria and neutral lipids. 10 μg mL-1 of PFNA had a severe negative effect on blastocyst formation (OR: 0.27 p < 0.05), an effect not observed at 0.1 μg mL-1. However, lipid droplet distribution was significantly altered in embryos exposed to 0.1 μg mL-1, suggesting a disturbance of lipid metabolism after exposure to sublethal levels of PFNA during oocyte maturation in vitro.
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| 9. |
- Heindel, Jerrold J., et al.
(author)
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NIEHS/FDA CLARITY-BPA research program update
- 2015
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In: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 58, s. 33-44
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Research review (peer-reviewed)abstract
- Bisphenol A (BPA) is a chemical used in the production of numerous consumer products resulting in potential daily human exposure to this chemical. The FDA previously evaluated the body of BPA toxicology data and determined that BPA is safe at current exposure levels. Although consistent with the assessment of some other regulatory agencies around the world, this determination of BPA safety continues to be debated in scientific and popular publications, resulting in conflicting messages to the public. Thus, the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S. Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively a variety of hypothesis-based research investigations and guideline-compliant safety testing with BPA. This collaboration is known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). This paper provides a detailed description of the conduct of the study and a midterm update on progress of the CLARITY-BPA research program.
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| 11. |
- Källén, Bengt, et al.
(author)
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Use of tramadol in early pregnancy and congenital malformation risk
- 2015
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In: Reproductive Toxicology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0890-6238 .- 1873-1708. ; 58, s. 246-251
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Journal article (peer-reviewed)abstract
- Only few studies exist regarding the risk of a teratogenic effect of tramadol when used in early pregnancy. Using the Swedish Medical Birth Register, women (deliveries in 1997-2013) who had reported the use of tramadol in early pregnancy were identified. Maternal characteristics and concomitant drug use were analyzed. Among 1,682,846 women (1,797,678 infants), 1751 (1776 infants) had used tramadol, 96 of the infants had a congenital malformation and 70 of them were relatively severe. The adjusted odds ratio for a relatively severe malformation was 1.33 (95% CI 1.05-1.70). The odds ratios for cardiovascular defects (1.56, 95% CI 1.04-2.29) and for pes equinovarus (3.63, 95% CI 1.61-6.89) were significantly increased. The study suggests a teratogenic effect of tramadol but the risk increase is moderate. (C) 2015 Elsevier Inc. All rights reserved.
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| 14. |
- Specht, Ina Olmer, et al.
(author)
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Environmental Hexachlorobenzene exposure and human male reproductive function.
- 2015
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In: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 58:Jul 22, s. 8-14
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Journal article (peer-reviewed)abstract
- Hexachlorobenzene (HCB) is a persistent environmental fungicide that may disrupt androgen regulation. The aim of this study was to investigate associations between HCB levels and biomarkers of male reproductive function. 589 spouses of pregnant women from Greenland, Poland and Ukraine were enrolled between 2002 and 2004. The men provided semen and blood samples and were interviewed. HCB was measured in serum by gas chromatography. The mean serum concentrations of HCB were higher in Ukraine (182.3 ng/g lipid) and Greenland (79.0 ng/g lipid) compared to Poland (14.2 ng/g lipid). Sex Hormone Binding Globulin (SHBG) and Free Androgen Index (FAI) were associated with HCB in men from Ukraine and Poland. This study spanning large differences in environmental HCB exposure levels shows a positive association for SHBG and negative association for FAI with high serum levels of HCB in fertile men, but without major consequences for semen quality and the Inuit study population.
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| 15. |
- Spörndly-Nees, Ellinor, et al.
(author)
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Low-dose exposure to Bisphenol A during development has limited effects on male reproduction in midpubertal and aging Fischer 344 rats.
- 2018
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 81, s. 196-206
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Journal article (peer-reviewed)abstract
- Low doses of Bisphenol A (BPA) during development may affect reproduction. In this study, Fischer 344 rats were exposed to 0.5 or 50 μg BPA/kg bw/day via drinking water from gestational day 3.5 to postnatal day 22. Anogenital distance, organ weight, histopathology of reproductive organs, hormone analysis and sperm morphology were evaluated in male offspring. In this study no major effects of BPA on male reproduction in midpubertal (postnatal day 35) or adult (12-month-old) rats were revealed, apart from a higher prevalence of mild inflammatory cell infiltrate in cauda epididymis in adult rats exposed to 50 μg BPA/kg bw/day. No BPA-related effects on sexual development were seen but care should be taken when evaluating histopathology in midpuberty testis due to large morphological variation. Results from the present study show no major signs of altered male reproduction in rats exposed to low doses of BPA during gestation and lactation.
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| 16. |
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| 17. |
- Brownbill, Paul, et al.
(author)
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An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy
- 2016
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238. ; 64, s. 191-202
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Journal article (peer-reviewed)abstract
- The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, “PlaNet”, will bridge academia, industry and regulators to consider screen ability and standardisation issues surrounding these models, with proven reproducibility for introduction into industrial and clinical practice.
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| 18. |
- Ek, C. Joakim, et al.
(author)
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Expression of tight junction proteins and transporters for xenobiotic metabolism at the blood-CSF barrier during development in the nonhuman primate (P. hamadryas)
- 2015
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238. ; 56, s. 32-44
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Journal article (peer-reviewed)abstract
- The choroid plexus (CP) is rich in barrier mechanisms including transporters and enzymes which can influence drug disposition between blood and brain. We have limited knowledge of their state in fetus. We have studied barrier mechanisms along with metabolism and transporters influencing xenobiotics, using RNAseq and protein analysis, in the CP during the second-half of gestation in a nonhuman primate (Papio hamadryas). There were no differences in the expression of the tight-junctions at the CP suggesting a well-formed fetal blood-CSF barrier during this period of gestation. Further, the fetal CP express many enzymes for phase I-III metabolisms as well as transporters suggesting that it can greatly influence drug disposition and has a significant machinery to deactivate reactive molecules with only minor gestational changes. In summary, the study suggests that from, at least, midgestation, the CP in the nonhuman primate is restrictive and express most known genes associated with barrier function and transport.
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| 19. |
- Baricz, Árpád, et al.
(author)
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The Hurwitz-type theorem for the regular Coulomb wave function via Hankel determinants
- 2018
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In: Linear Algebra and its Applications. - : Elsevier BV. - 0024-3795 .- 1873-1856. ; 548, s. 259-272
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Journal article (peer-reviewed)abstract
- We derive a closed formula for the determinant of the Hankel matrix whose entries are given by sums of negative powers of the zeros of the regular Coulomb wave function. This new identity applied together with results of Grommer and Chebotarev allows us to prove a Hurwitz-type theorem about the zeros of the regular Coulomb wave function. As a particular case, we obtain a new proof of the classical Hurwitz's theorem from the theory of Bessel functions that is based on algebraic arguments. In addition, several Hankel determinants with entries given by the Rayleigh function and Bernoulli numbers are also evaluated.
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| 20. |
- Cianchi, Andrea, et al.
(author)
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Quasilincar elliptic problems with general growth and merely integrable, or measure, data
- 2017
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In: Nonlinear Analysis. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0362-546X .- 1873-5215. ; 164, s. 189-215
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Journal article (peer-reviewed)abstract
- Boundary value problems for a class of quasilinear elliptic equations, with an Orlicz type growth and L-1 right-hand side are considered. Both Dirichlet and Neumann problems are contemplated. Existence and uniqueness of generalized solutions, as well as their regularity, are established. The case of measure right-hand sides is also analyzed. (C) 2017 Published by Elsevier Ltd.
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| 21. |
- Galrinho, Miguel, et al.
(author)
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Estimating models with high-order noise dynamics using semi-parametric weighted null-space fitting
- 2019
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In: Automatica. - : Elsevier. - 0005-1098 .- 1873-2836. ; 102, s. 45-57
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Journal article (peer-reviewed)abstract
- Standard system identification methods often provide inconsistent estimates with closed-loop data. With the prediction error method (PEM), this issue is solved by using a noise model that is flexible enough to capture the noise spectrum. However, a too flexible noise model (i.e., too many parameters) increases the model complexity, which can cause additional numerical problems for PEM. In this paper, we consider the weighted null-space fitting (WNSF) method. With this method, the system is first modeled using a non-parametric ARX model, which is then reduced to a parametric model of interest using weighted least squares. In the reduction step, a parametric noise model does not need to be estimated if it is not of interest. Because the flexibility of the noise model is increased with the sample size, this will still provide consistent estimates in closed loop and asymptotically efficient estimates in open loop. In this paper, we prove these results, and we derive the asymptotic covariance for the estimation error obtained in closed loop, which is optimal for an infinite-order noise model. For this purpose, we also derive a new technical result for geometric variance analysis, instrumental to our end. Finally, we perform a simulation study to illustrate the benefits of the method when the noise model cannot be parametrized by a low-order model.
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| 22. |
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| 23. |
- Mu, Biqiang, et al.
(author)
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On input design for regularized LTI system identification: Power-constrained input
- 2018
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In: Automatica. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0005-1098 .- 1873-2836. ; 97, s. 327-338
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Journal article (peer-reviewed)abstract
- Input design is an important issue for classical system identification methods but has not been investigated for the kernel-based regularization method (KRM) until very recently. In this paper, we consider the input design problem of KRMs for LTI system identification. Different from the recent result, we adopt a Bayesian perspective and in particular make use of scalar measures (e.g., the A-optimality, D-optimality, and E-optimality) of the Bayesian mean square error matrix as the design criteria subject to power-constraint on the input. Instead of solving the optimization problem directly, we propose a two-step procedure. In the first step, by making suitable assumptions on the unknown input, we construct a quadratic map (transformation) of the input such that the transformed input design problems are convex, and the global minima of the transformed input design problem can thus be found efficiently by applying well-developed convex optimization software packages. In the second step, we derive the characterization of the optimal input based on the global minima found in the first step by solving the inverse image of the quadratic map. In addition, we derive analytic results for some special types of kernels, which provide insights on the input design and also its dependence on the kernel structure. (C) 2018 Elsevier Ltd. All rights reserved.
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| 24. |
- Thunberg, Johan, et al.
(author)
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Dynamic controllers for column synchronization of rotation matrices : A QR-factorization approach
- 2018
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In: Automatica. - Oxford : Pergamon Press. - 0005-1098 .- 1873-2836. ; 93, s. 20-25
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Journal article (peer-reviewed)abstract
- In the multi-agent systems setting, this paper addresses continuous-time distributed synchronization of columns of rotation matrices. More precisely, k specific columns shall be synchronized and only the corresponding k columns of the relative rotations between the agents are assumed to be available for the control design. When one specific column is considered, the problem is equivalent to synchronization on the (d−1)-dimensional unit sphere and when all the columns are considered, the problem is equivalent to synchronization on SO(d). We design dynamic control laws for these synchronization problems. The control laws are based on the introduction of auxiliary variables in combination with a QR-factorization approach. The benefit of this QR-factorization approach is that we can decouple the dynamics for the k columns from the remaining d−k ones. Under the control scheme, the closed loop system achieves almost global convergence to synchronization for quasi-strong interaction graph topologies.
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