| 1. |
- Akram, Frida Hosseini, et al.
(författare)
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Incidence of Subclinical Hypothyroidism and Hypothyroidism in Early Pregnancy
- 2017
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Ingår i: Journal of Women's Health. - : Mary Ann Liebert Inc. - 1540-9996 .- 1931-843X. ; 26:11, s. 1231-1235
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Tidskriftsartikel (refereegranskat)abstract
- Background: Untreated and subclinical hypothyroidism (SCH) has been associated with adverse pregnancy complications such as increased risk of miscarriage, hypertension, preeclampsia, and preterm delivery. However, in Sweden, screening for thyroid dysfunction during pregnancy is only recommended for women with a high risk of thyroid disease. Therefore, the aim of this study was to determine the incidence of clinical and SCH in women in the first trimester of pregnancy.Materials and Methods: In this prospective study, 1298 pregnant women were divided into three groups: one unselected general screening group (n=611), one low-risk group comprising women without risk factors for thyroid disorder (n=511), and one high-risk group comprising women with an inheritance or suspicion of thyroid disease or undergoing treatment for thyroid disease (n=88). Serum was obtained up to gestational week 13, and thyrotropin (TSH) was analyzed.Results: The incidences of thyroid dysfunction in the three screening groups were 9.8% in the general screening group, 9.6% in the low-risk group, and 10.2%, p=0.948, in the high-risk group. In the women with known hypothyroidism on levothyroxine treatment, 50.6% had serum TSH levels above 2.0mIU/L.Conclusions: High-risk screening is not useful in predicting which women are at risk of thyroid disease in early pregnancy since approximate to 10% of women with SCH or hypothyroidism could not be diagnosed in this way.
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| 2. |
- Altmae, Signe, et al.
(författare)
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Interactome of Human Embryo Implantation : Identification of Gene Expression Pathways, Regulation, and Integrated Regulatory Networks
- 2012
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Ingår i: Molecular Endocrinology. - : The Endocrine Society. - 0888-8809 .- 1944-9917. ; 26:1, s. 203-217
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Tidskriftsartikel (refereegranskat)abstract
- A prerequisite for successful embryo implantation is adequate preparation of receptive endometrium and the establishment and maintenance of a viable embryo. The success of implantation further relies upon a two-way dialogue between the embryo and uterus. However, molecular bases of these preimplantation and implantation processes in humans are not well known. We performed genome expression analyses of humanembryos (n = 128) andhumanendometria (n = 8). We integrated these data with protein-protein interactions in order to identify molecular networks within the endometrium and the embryo, and potential embryo-endometrium interactions at the time of implantation. For that, we applied a novel network profiling algorithm HyperModules, which combines topological module identification and functional enrichment analysis. We found a major wave of transcriptional down-regulation in preimplantation embryos. In receptive-stage endometrium, several genes and signaling pathways were identified, including JAK-STAT signaling and inflammatory pathways. The main curated embryo-endometrium interaction network highlighted the importance of cell adhesion molecules in the implantation process. We also identified cytokine-cytokine receptor interactions involved in implantation, where osteopontin (SPP1), leukemia inhibitory factor (LIF) and leptin (LEP) pathways were intertwining. Further, we identified a number of novel players in human embryo-endometrium interactions, such as apolipoprotein D (APOD), endothelin 1 (END1), fibroblast growth factor 7 (FGF7), gastrin (GAST), kringle containing trnasmembrane protein 1 (KREMEN1), neuropilin 1 (NRP1), serpin peptidase inhibitor clade A member 3 (SERPINA3), versican (VCAN), and others. Our findings provide a fundamental resource for better understanding of the genetic network that leads to successful embryo implantation. We demonstrate the first systems biology approach into the complex molecular network of the implantation process in humans.
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| 3. |
- Altmäe, Signe, 1978-, et al.
(författare)
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MicroRNAs miR-30b, miR-30d, and miR-494 Regulate Human Endometrial Receptivity
- 2013
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 20:3, s. 308-317
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs (miRNAs) act as important epigenetic posttranscriptional regulators of gene expression. We aimed to gain more understanding of the complex gene expression regulation of endometrial receptivity by analyzing miRNA signatures of fertile human endometria. We set up to analyze miRNA signatures of receptive (LH + 7, n = 4) versus prereceptive (LH + 2, n = 5) endometrium from healthy fertile women. We found hsa-miR-30b and hsa-miR-30d to be significantly upregulated, and hsa-miR-494 and hsa-miR-923 to be downregulated in receptive endometrium. Three algorithms (miRanda, PicTar, and TargetScan) were used for target gene prediction. Functional analyses of the targets using Ingenuity Pathways Analysis and The Database for Annotation, Visualization and Integrated Discovery indicated roles in transcription, cell proliferation and apoptosis, and significant involvement in several relevant pathways, such as axon guidance, Wnt/β-catenin, ERK/MAPK, transforming growth factor β (TGF-β), p53 and leukocyte extravasation. Comparison of predicted miRNA target genes and our previous messenger RNA microarray data resulted in a list of 12 genes, including CAST, CFTR, FGFR2, and LIF that could serve as a panel of genes important for endometrial receptivity. In conclusion, we suggest that a subset of miRNAs and their target genes may play important roles in endometrial receptivity.
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| 4. |
- Altmäe, Signe, et al.
(författare)
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Variation in Hyaluronan-Binding Protein 2 (HABP2) Promoter Region is Associated With Unexplained Female Infertility
- 2011
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 18:5, s. 485-492
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Tidskriftsartikel (refereegranskat)abstract
- We set up to analyze polymorphisms in hyaluronan-binding protein 2 (HABP2) gene in healthy fertile women (n = 158) and in women with unexplained infertility (n = 116) and to investigate the potential role of HABP2 in receptive endometrium. Minor rs1157916 A and the major rs2240879 A alleles together with AA genotypes were significantly less frequent in infertile women than in controls. Immunohistochemistry analysis of endometrial HABP2 expression at the time of implantation identified significantly lower HABP2 protein level in infertile women in stroma and vessels than in fertile women. Migration assay analysis of cultured trophoblast and endothelial cells toward HABP2 protein referred to the function of HABP2 in endometrial endothelial cells. In conclusion, our results indicate that polymorphisms in the regulatory region of HABP2 gene could influence gene expression levels in the receptive endometrium and could thereby be one reason for infertility complications in women with unexplained infertility. Additionally, HABP2 protein involvement in endometrial angiogenesis is proposed.
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| 5. |
- Baumgart, Juliane, 1978-, et al.
(författare)
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Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer
- 2013
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Ingår i: Menopause. - : Lippincott Williams & Wilkins. - 1072-3714 .- 1530-0374. ; 20:2, s. 162-168
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The goal of this study was to investigate sexual function in postmenopausal breast cancer patients treated with aromatase inhibitors.Methods: A population-based, cross-sectional study was conducted among postmenopausal breast cancer patients on adjuvant endocrine treatment and age-matched controls with and without estrogen treatment. Sexual function was assessed with a standardized questionnaire.Results: In all, 42.4% of aromatase inhibitor-treated breast cancer patients were dissatisfied with their sex life in general, and 50.0% reported low sexual interest; this was significantly more common than in tamoxifen-treated patients and controls (P < 0.05). Aromatase inhibitorYtreated patients reported insufficient lubrication in 73.9% and dyspareunia in 56.5% of cases, which were significantly more common than in controls, irrespective of hormonal use (P < 0.05). Tamoxifen-treated patients reported significantly more dyspareunia (31.3%; P < 0.05) but resembled controls in all other concerns.Conclusions: Our findings suggest that sexual dysfunction in aromatase inhibitorYtreated women is a greatly underestimated problem.
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| 6. |
- Granfors, Michaela, 1972-, et al.
(författare)
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Phosphodiesterase 8B gene polymorphism in women with recurrent miscarriage : A retrospective case control study.
- 2012
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 13, s. 121-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recurrent miscarriage affects approximately 1% of all couples. There is a known relation between hypothyroidism and recurrent miscarriage. Phosphodiesterase 8B (PDE8B) is a regulator of cyclic adenosine monophosphate (cAMP) with important influence on human thyroid metabolism. Single nucleotide polymorphism (SNP) rs 4704397 in the PDE8B gene has been shown to be associated with variations in serum Thyroid Stimulating Hormone (TSH) and thyroxine (T4) levels. The aim of this study was to investigate whether there is an association between the SNP rs 4704397 in the PDE8B gene and recurrent miscarriage. METHODS: The study was designed as a retrospective case control study. 188 cases with recurrent miscarriage were included and compared with 391 controls who had delivered at least once and with no history of miscarriage or assisted reproduction. RESULTS: No difference between cases and controls concerning age was found. Bivariate associations between homozygous A/A (OR 1.57, 95% CI 0.98-2.52) as well as G/G carriers (OR 1.52, 95% CI 1.02-2.25) of SNP rs 4704397 in PDE8B and recurrent miscarriage were verified (test for trend across all 3 genotypes, p = 0.059). After adjustment for known confounders such as age, BMI and smoking the association between homozygous A/A (AOR 1.63, 95% CI 1.01 - 2.64, p = 0.045) and G/G (AOR 1.52, 95% CI 1.02 - 2.27, p = 0.039) carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage remained. CONCLUSIONS: Our findings suggest that there is an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage.
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| 7. |
- Hambiliki, Fredwell, et al.
(författare)
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Co-localization of NANOG and OCT4 in human pre-implantation embryos and in human embryonic stem cells
- 2012
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Ingår i: Journal of Assisted Reproduction and Genetics. - : Springer Science and Business Media LLC. - 1058-0468 .- 1573-7330. ; 29:10, s. 1021-1028
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:NANOG and OCT4 are required for the maintenance of pluripotency in embryonic stem cells (ESCs). These proteins are also expressed in the inner cell mass (ICM) of the mouse pre-implantation embryo.METHODS:Immunohistochemistry was used to show the presence of NANOG and OCT4 protein, and in situ hybridization was used to localize NANOG mRNA in human embryos from two-cell to blastocyst stage, and in human ESCs (hESCs).RESULTS:Nanog and Oct4 were co-localized in human embryos from morula and blastocyst stages. NANOG mRNA was detected in a group of cells in the morula, in cells of the ICM of blastocysts, and evenly in hESCs. All non-differentiated hESCs expressed NANOG and OCT4 protein. Pluripotent cells expressing NANOG and Oct4 were eccentrically localized, probably in polarized cells in a human compacted morula, which appears to be different from expression in murine embryos.CONCLUSION:In this study, we demonstrate that whole mount in situ hybridization is amenable to localization of mRNAs in human development, as in other species.
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| 8. |
- Hambiliki, F., et al.
(författare)
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Glycoprotein 130 promotes human blastocyst development in vitro
- 2013
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 99:6, s. 1592-U444
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the efficacy of leukemia inhibitory factor (LIF) and/or glycoprotein 130 Design: Laboratory study. Setting: University hospital-based IVF clinic. Patient(s): A total of 164 frozen embryos that survived thawing were cultured in media supplemented Intervention(s): Morphological development was evaluated by light microscopy. Protein expression Main Outcome Measure(s): Embryo development and protein content. Result(s): Addition of gp130 to culture media improved blastocyst formation (73% vs. 43%). Addition of Conclusion(s): Glycoprotein 130, but not LIF, seems to be beneficial for preimplantation embryo
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| 9. |
- Helmestam, Malin, 1982-, et al.
(författare)
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Tamoxifen Modulates Cell Migration and Expression of Angiogenesis-Related Genes in Human Endometrial Endothelial Cells
- 2012
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 180:6, s. 2527-2535
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Tidskriftsartikel (refereegranskat)abstract
- The selective estrogen receptor modulator tamoxifen is used for the prevention and treatment of breast cancer. The adverse effects of tamoxifen include vaginal endometrial bleeding, endometrial hyperplasia, and cancer, conditions associated with angiogenesis. The aim of this study was to examine the effects of tamoxifen on cell migration and angiogenesis-related gene expression in human endometrial endothelial cells (HEECs). The regulatory effects of tamoxifen on endometrial stromal cells and HEECs were also examined. HEECs and stromal cells were isolated and grown In monocultures or co-cultures, and incubated with 0.1 to 100 mu mol/L tamoxifen for 48 hours. Quantitative PCR demonstrated that tamoxifen decreased the mRNA expression of vascular endothelial growth factor-A (VEGF-A) and increased the mRNA expression of VEGF receptor-1 and placental growth factor (PLGF) in HEECs. Tamoxifen's effects on VEGF-A were inhibited when HEECs were co-cultured with stromal cells. In addition, tamoxifen reduced VEGF-induced HEEC migration. The tamoxifen-metabolizing enzymes CYP1A1 and CYP1B1 were detected by immunohistochemistry in and around endometrial blood vessels and by quantitative PCR in HEECs. Our data suggest that tamoxifen changes the regulation of angiogenesis in the endometrium, likely by reducing angiogenic activity. The results also indicate that endometrial stromal cells regulate some of tamoxifen's effects in HEECs, and the presence of tamoxifen-metabolizing enzymes suggests tamoxifen bioactivation in the endometrial vasculature in vivo. These findings may help to elucidate the mechanism of the bleeding disturbances associated with tamoxifen treatment.
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| 10. |
- Husseini-Akram, Frida, et al.
(författare)
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Hyaluronan-binding protein 2 (HABP2) gene variation in women with recurrent miscarriage
- 2018
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Ingår i: BMC Women's Health. - : Springer Science and Business Media LLC. - 1472-6874. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background:Idiopathic recurrent miscarriage, defined as three or more consecutive miscarriages, is a distressing early pregnancy complication. Although, the etiology of recurrent miscarriage is still unknown, an aberrant regulation of the endometrial receptivity marker hyaluronan-binding protein 2 (HABP2) has been suggested. The objective of the present study was to investigate the effect of genetic variations of HABP2 in women with idiopathic recurrent miscarriage compared to fertile women.Methods:This study was designed as a case-control study. In total, 165 women who had three or more consecutive miscarriages and 289 fertile women were included in the study. Polymorphisms in the HABP2 gene were analyzed using TaqMan SNP Genotyping Assays. Three polymorphisms in the HABP2 gene, rs1157916, rs2240879 and rs7080536 (Marburg I) were studied.Results:Polymorphism in HABP2 showed no significant difference in women with recurrent miscarriage compared to fertile women, except for rs1157916 minor A allele that was more prevalent among RM patients (p = 0.058). Significantly higher live birth rate was observed among women with three to four miscarriages compared to those with more miscarriages (p = 0.001).Conclusions:Variations in the HABP2 gene did not seem to be involved in the etiology of recurrent miscarriage, while, the number of previous miscarriages had an impact on the live birth rate.
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