| 11. |
- Bredhult, Carolina, et al.
(författare)
-
Gene expression analysis of human endometrial endothelial cells exposed to Bisphenol A
- 2009
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 28:1, s. 18-25
-
Tidskriftsartikel (refereegranskat)abstract
- Bisphenol A (BPA) can affect reproductive tissues in several species. Recently, treatment of human endometrial endothelial cells (HEECs) with 100 microM BPA decreased their proliferation and viability. In the present study, 50 microM BPA decreased HEEC proliferation, and microarray analyses of five HEEC cultures revealed that BPA affected biological processes associated with proliferation. Expression of three of the most differentially expressed genes identified in the gene array analysis, SPBC25, SGOL2 and CDCA8, was verified by real-time qRT-PCR in five HEEC cultures obtained from women in the proliferative phase and in five cultures obtained from women in the secretory phase of the menstrual cycle after treatment with BPA. This study supports our previous findings of decreased cell proliferation and increased cell death in response to BPA, and may offer important clues to the mechanisms of action of BPA. Furthermore, the study implies a possible impact of BPA on female fertility functions.
|
|
| 12. |
- Bredhult, Carolina, et al.
(författare)
-
Study of the relation between the incidence of uterine leiomyomas and the concentrations of PCB and DDT in Baltic gray seals
- 2008
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 25:2, s. 247-255
-
Tidskriftsartikel (refereegranskat)abstract
- Exposure to environmental contaminants is believed to be associated with the previously described decrease in the reproduction rate of Baltic gray seals. In the present study the prevalence of uterine leiomyomas was investigated in 257 Baltic gray seal females examined during 1973-2007, in relation to the levels of polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) in Baltic biota, using an estimated exposure index. Additionally, the proliferative activity in leiomyomas, occurrence of corpora lutea, and blubber concentrations of PCB and DDT were investigated in a subset of females. Leiomyomas were only found in females 22-41 years old, at a prevalence of 65%. No differences in blubber concentrations of PCB or DDT were detected between the subset of leiomyoma-bearing females and reference females, but the estimated exposure index indicated that the PCB level in Baltic biota might be related to the leiomyoma prevalence in Baltic gray seal females.
|
|
| 13. |
- Brokken, Leon, et al.
(författare)
-
Interactions between polymorphisms in the aryl hydrocarbon receptor signalling pathway and exposure to persistent organochlorine pollutants affect human semen quality.
- 2014
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 49:Jul 30, s. 65-73
-
Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPs) may affect male reproductive function. Many dioxin-like POPs exert their effects by activation of the aryl hydrocarbon receptor (AHR) signalling pathway. We analysed whether gene-environment interactions between polymorphisms in AHR (R554K) and AHR repressor (AHRR P185A) and serum levels of markers of POP exposure 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (p,p'-DDE) and 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) are associated with 21 parameters of male reproductive function in 581 proven-fertile European and Greenlandic men. In Greenlandic men, AHR variants significantly modified the association between serum levels of both p,p'-DDE and CB-153 and inhibin B levels, sperm chromatin integrity, and seminal zinc levels. In the total cohort, interactions between AHRR variants and serum levels of CB-153 were associated with sperm chromatin integrity and the expression of the pro-apoptotic marker protein Fas. The data indicate that susceptibility to adverse effects of POP exposure on male reproductive function is dependent on polymorphisms in genes involved in AHR signalling.
|
|
| 14. |
|
|
| 15. |
- Carlsson, Gunnar, et al.
(författare)
-
Developmental toxicity of albendazole and its three main metabolites in zebrafish embryos
- 2011
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 32, s. 129-137
-
Tidskriftsartikel (refereegranskat)abstract
- Albendazole (ABZ) is used as an anthelmintic drug in humans and animals. ABZ has been shown to cause developmental toxicity in experimental animals, however it is not clear if this is caused by the parent compound or a metabolite. Zebrafish embryos were exposed from 1 to 144 hpf (hours post fertilization) to investigate the developmental toxicity of ABZ, the first metabolite albendazole sulphoxide and the subsequent metabolites albendazole sulphone (ABZSO(2)) and albendazole-2-aminosulphone (ABZSO(2)NH(2)). The results showed that ABZ caused malformations of head and tail and embryonic lethality from 0.3 mu M. In contrast, the metabolites did not display developmental toxicity at any tested concentration. Dechorionation did not influence the developmental toxic potential of ABZ and ABZSO, indicating that bioavailability was not a limiting factor. Chemical analysis showed that at sublethal concentrations, most of ABZ was metabolized to ABZSO. The results demonstrate that in zebrafish embryos ABZ rather than ABZSO displays developmental toxicity. (C) 2011 Elsevier Inc. All rights reserved.
|
|
| 16. |
- Chelslín, Felix, 1991-, et al.
(författare)
-
Smoking during pregnancy is associated with the placental proteome
- 2023
-
Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 119
-
Tidskriftsartikel (refereegranskat)abstract
- Maternal smoking during pregnancy (MSDP) is a significant risk factor for the development of foetal, neonatal, and childhood morbidities. We hypothesized that infants exposed to MSDP have a distinct proteomic expression in their term placentas compared to infants without such an exposure. A total of 39 infants exposed (cord blood cotinine levels of >1ng/ml) and 44 infants not exposed to MSDP were included in the study. Women with chronic disease, body mass index of >30, or a history of uterine surgery were excluded. Total proteome abundance was analysed with quantitative mass spectrometry. For univariate analysis of differences in placental protein levels between groups, ANOVA with multiple testing corrections by the Benjamini-Hochberg method was used. For multivariate analysis, we used principal component analysis, partial least squares, lasso, random forest, and neural networks. The univariate analyses showed four differentially abundant proteins (PXDN, CYP1A1, GPR183, and KRT81) when heavy and moderate smoking groups were compared to non-smokers. With the help of machine learning, we found that an additional six proteins (SEPTIN3, CRAT, NAAA, CD248, CADM3, and ZNF648) were discriminants of MSDP. The placental abundance of these ten proteins together explained 74.1% of the variation in cord blood cotinine levels (p = 0.002). Infants exposed to MSDP showed differential abundance of proteins in term placentas. We report differential placental abundance of several proteins for the first time in the setting of MSDP. We believe that these findings supplement the current understanding of how MSDP affects the placental proteome.
|
|
| 17. |
- Christensen, P S, et al.
(författare)
-
Environmental cadmium and lead exposure and anti-Müllerian hormone in pregnant women
- 2016
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 61, s. 114-119
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 18. |
|
|
| 19. |
- Danielsson, Bengt R., et al.
(författare)
-
Embryonic cardiac arrhythmia and generation of reactive oxygen species : common teratogenic mechanism for IKr blocking drugs
- 2007
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 24:1, s. 42-56
-
Tidskriftsartikel (refereegranskat)abstract
- In the adult organism, it is well established that hypoxia followed by reperfusion may be fatal and result in generation of reactive oxygen species (ROS) and subsequent tissue damage. There is also considerable evidence that temporary decrease or interruption in oxygen supply to the embryo and ROS generation during reperfusion result in tissue damage in embryonic tissues. A wide spectrum of different malformations by transient embryonic hypoxia could be produced, depending on the duration, extent, and timing of the hypoxic event. It is the contention of this paper that drugs that block the potassium channel IKr, either as an intended pharmacologic effect or as an unwanted side-effect, are potentially teratogenic by a common ROS related mechanism. Drugs blocking the IKr channel, such as almokalant, dofetilide, phenytoin, cisapride and astemizole, do all produce a similar pattern of hypoxia-related malformations. Mechanistic studies show that the malformations are preceded by embryonic cardiac arrhythmia and periods of hypoxia/reoxygenation in embryonic tissues. Pretreatment or simultaneous treatment with radical scavengers with capacity to capture ROS, markedly decrease the teratogenicity of different IKr blocking drugs. A second aim of this review is to demonstrate that the conventional design of teratology studies is not optimal to detect malformations caused by IKr blocking drugs. Repeated high doses result in high incidences of embryonic death due embryonic cardiac arrhythmia, thus masking their teratogenic potential. Instead, single dosing on specific days is proposed to be a better way to characterize the teratogenic potential of Ikr blocking drugs.
|
|
| 20. |
- Danielsson, Bengt, et al.
(författare)
-
Use of ondansetron during pregnancy and congenital malformations in the infant.
- 2014
-
Ingår i: Reproductive Toxicology. - : Elsevier BV. - 1873-1708 .- 0890-6238. ; 50, s. 134-137
-
Tidskriftsartikel (refereegranskat)abstract
- The study investigates teratogenic risks with ondansetron (Zofran(®)). Data from the Swedish Medical Birth Register combined with the Swedish Register of Prescribed Drugs were used to identify 1349 infants born of women who had taken ondansetron in early pregnancy, 1998-2012. Presence of congenital malformations in the offspring was identified with three national health registers. In a Mantel-Haenszel analysis adjustment was made for year of delivery, maternal age, parity, smoking in early pregnancy and pre-pregnancy body mass index. Risks were expressed as odds or risk ratios with 95% confidence intervals. No statistically significantly increased risk for a major malformation was found. The risks for a cardiovascular defect and notably a cardiac septum defect were increased and statistically significant (OR=1.62, 95% CI 1.04-2.14, and RR 2.05, 95% CI 1.19-3.28, respective). The teratogenic risk with ondansetron is low but an increased risk for a cardiac septum defect is likely.
|
|
