| 1. |
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| 2. |
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| 3. |
- Aghajanova, Lusine, et al.
(författare)
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Diminished endometrial expression of ghrelin and ghrelin receptor contributes to infertility
- 2010
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Ingår i: Reproductive sciences (Thousand Oaks, Calif.). - : Springer Science and Business Media LLC. - 1933-7205 .- 1933-7191. ; 17:9, s. 823-832
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Tidskriftsartikel (refereegranskat)abstract
- The objectives were to investigate the presence, distribution and sex steroid hormone regulation of ghrelin and its receptor, growth hormone secretagogue receptor (GHSR), in human endometrium in relation to endometrial receptivity and fertility. Endometrial biopsies were obtained from women with unexplained infertility and healthy fertile volunteers. Ishikawa cells were used to mimic the action of ghrelin in endometrium. Immunostaining of GHSR was strong in luminal epithelium and stroma during mid-secretory phase. Ghrelin and GHSR expression is less intense in mid-secretory endometrium of infertile women compared to fertile controls. Treatment with estrogen and/or progesterone or their antagonists did not significantly change the relative expression of GHSR in Ishikawa and stromal cells. Ghrelin was present in and secreted from human blastocysts, which suggest that the communication between human blastocyst and endometrium might involve ghrelin. Low levels of GHSR in endometrium from women with unexplained infertility may in part explain the infertility.
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| 4. |
- Aghajanova, Lusine, et al.
(författare)
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HB-EGF but not amphiregulin or their receptors HER1 and HER4 is altered in endometrium of women with unexplained infertility
- 2008
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 15:5, s. 484-92
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Tidskriftsartikel (refereegranskat)abstract
- Heparin-binding, epidermal growth factor-like growth factor (HB-EGF) and its receptors (HER I and HER4) play a role in the human implantation process. Amphiregulin is a member of the EGF family but with unknown function in human fertility. It has been suggested that some women with unexplained infertility have defective endometrial development. The aim of this study is to determine the presence of amphiregulin and the receptors HER1 and HER4 in normal human endometrium throughout the menstrual cycle. In addition) the present study aims to compare endometrium from women with unexplained infertility with endometrium from women with male factor infertility and healthy fertile controls. Immunohistochemistry and real-time polymerase chain reaction were used to determine the expression of HB-EGF, HER 1, HER4, and amphiregulin. The stromal staining of HER I and the epithelial staining of HER4 were most intense in the mid- and late-secretory-phase endometrium. Amphiregulin did not vary during the menstrual cycle. In the mid-secretory phase, the protein expression of HB-EGF was lower in endometrium from women with unexplained infertility versus normal endometrium and endometrium from women with malefactor infertility. HB-EGF and HER4 mRNA expression in mid-secretory endometrium of women with unexplained and malefactor infertility were increased compared with normal controls. Impaired endometrial expression of certain members of the EGF family may contribute to infertility in some women with unexplained infertility.
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| 5. |
- Ahlsson, Fredrik, et al.
(författare)
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Gene Expression in Placentas From Nondiabetic Women Giving Birth to Large for Gestational Age Infants
- 2015
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 22:10, s. 1281-1288
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Tidskriftsartikel (refereegranskat)abstract
- Gestational diabetes, obesity, and excessive weight gain are known independent risk factors for the birth of a large for gestational age (LGA) infant. However, only 1 of the 10 infants born LGA is born by mothers with diabetes or obesity. Thus, the aim of the present study was to compare placental gene expression between healthy, nondiabetic mothers (n = 22) giving birth to LGA infants and body mass index-matched mothers (n = 24) giving birth to appropriate for gestational age infants. In the whole gene expression analysis, only 29 genes were found to be differently expressed in LGA placentas. Top upregulated genes included insulin-like growth factor binding protein 1, aminolevulinate synthase 2, and prolactin, whereas top downregulated genes comprised leptin, gametocyte-specific factor 1, and collagen type XVII 1. Two enriched gene networks were identified, namely, (1) lipid metabolism, small molecule biochemistry, and organismal development and (2) cellular development, cellular growth, proliferation, and tumor morphology.
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| 6. |
- Alexopoulou, E., et al.
(författare)
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Embryo Morphokinetics and Blastocyst Development After GnRH Agonist versus hCG Triggering in Normo-ovulatory Women: a Secondary Analysis of a Multicenter Randomized Controlled Trial
- 2021
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 28, s. 2972-2981
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Tidskriftsartikel (refereegranskat)abstract
- Gonadotropin-releasing hormone agonist (GnRHa) for final oocyte maturation, along with vitrification of all usable embryos followed by transfer in a subsequent frozen-thawed cycle, is the most effective strategy to avoid ovarian hyperstimulation syndrome (OHSS). However, less is known about the ovulation induction triggers effect on early embryo development and blastocyst formation. This study is a secondary analysis of a multicenter, randomized controlled trial, with the aim to compare embryo development in normo-ovulatory women, randomized to GnRHa or human chorionic gonadotropin (hCG) trigger. In all, 4056 retrieved oocytes were observed, 1998 from the GnRHa group (216 women) and 2058 from the hCG group (218 women). A number of retrieved oocytes, mature and fertilized oocytes, and high-quality embryos and blastocysts were similar between the groups. A sub-analysis in 250 women enrolled at the main trial site including 2073 oocytes was conducted to compare embryo morphokinetics and cleavage patterns with EmbryoScope time-lapse system. In total, 1013 oocytes were retrieved from the GnRHa group (124 women) and 1060 oocytes were retrieved from the hCG group (126 women). Morphokinetic parameters and cleavage patterns were comparable between the groups. However, embryos derived from the GnRHa group were less likely to perform rolling during their development than the embryos from the hCG trigger group (OR = 0.41 (95%CI 0.25; 0.67), p-value 0.0003). The comparable results on embryo development and utilization rates between the GnRHa and hCG triggers is of clinical relevance to professionals and infertile patients, when GnRHa trigger and freeze-all is performed to avoid OHSS development. ClinicalTrials.gov Identifier: NCT02746562
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| 7. |
- 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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| 8. |
- Altmäe, Signe, et al.
(författare)
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Tissue Factor and Tissue Factor Pathway Inhibitors TFPI and TFPI2 in Human Secretory Endometrium - Possible Link to Female Infertility
- 2011
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 18:7, s. 666-678
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate tissue factor (TF) and its inhibitors TFPI and TFPI2 in secretory endometrium of fertile women and in women with unexplained infertility in relation to endometrial receptivity. In addition, common variation in the regulatory area of TF and TFPI genes was studied. Immunostaining of TF and TFPI, together with the appearance of pinopodes, revealed similar expression pattern in fertile endometrium throughout the secretory phase, being highest at the time of implantation. When compared protein expression levels at the time of implantation, infertile women demonstrated significantly higher TFPI expression in luminal epithelium. Furthermore, polymorphism TF -603 A/G was associated with the endometrial protein level in infertile women, being highest in women with GG genotype, and variation TFPI -287 T/C was associated with unexplained infertility, where infertile women presented more frequently T allele than fertile women. Contrary to TF and TFPI, TFPI2 showed different mRNA and protein expression patterns in fertile endometrium, and no differences between fertile and infertile women were detected. We conclude that the TF pathway is involved in normal endometrial maturation, where TF and TFPI seem to have important roles at the time of embryo implantation. Higher TFPI expression level during the time of embryo implantation and TFPI -287 T allele could be risk factors for unexplained infertility. No distinct involvement of TFPI2 in the regulation of endometrial receptivity and unexplained infertility was found.
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| 9. |
- 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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| 10. |
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| 11. |
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| 12. |
- Bergman, Lina, et al.
(författare)
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Plasma Levels of the Cerebral Biomarker, Neuron-Specific Enolase, are Elevated During Pregnancy in Women Developing Preeclampsia
- 2016
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 23:3, s. 395-400
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Neuron-specific enolase (NSE) is considered to be a peripheral biomarker of central nervous system injury. The aim of this study was to compare levels of NSE throughout pregnancy, in healthy pregnant women and in women developing preeclampsia. Methods: A nested case-control study within a longitudinal study cohort was performed. Four hundred sixty nine healthy pregnant women were enrolled, and plasma samples were collected at gestational weeks 10, 25, 28, 33, and 37. Levels of NSE were analyzed in 16 women with preeclampsia and 36 controls throughout pregnancy with an enzyme-linked immunosorbent assay. Results: In gestational week 37, women who developed preeclampsia had significantly higher plasma levels of NSE than healthy pregnant controls (P < .001). The levels of NSE did not change between gestational weeks 10 and 37 in women who developed preeclampsia, but the levels decreased significantly in healthy pregnant controls (P < .001). Conclusion: In pregnant women developing preeclampsia, the levels of NSE remained high throughout pregnancy, whereas in healthy women, these tended to decline over time, especially at the 2 last time points. The result might be confounded in early pregnancy by extracerebral sources of NSE, such as the corpus luteum. Findings need to be confirmed in a larger prospective study.
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| 13. |
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| 14. |
- Blad, Sofia, et al.
(författare)
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ECG and heart rate variability changes in preterm and near-term fetal lamb following LPS exposure.
- 2008
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Ingår i: Reproductive sciences (Thousand Oaks, Calif.). - : Springer Science and Business Media LLC. - 1933-7205 .- 1933-7191. ; 15:6, s. 572-83
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to evaluate the myocardial response in the preterm and near-term fetal lamb with infection. Chronically instrumented fetal lambs were exposed to lipopolysaccharide (LPS), and the fetal electrocardiogram (FECG) ST waveform was examined using STAN. Fetal heart rate variability (FHRV) was automatically analyzed by adapting a polynomial function to the RR sequence in the FECG. Preterm fetuses exposed to >90 ng/kg LPS died within 8 hours of LPS administration, a response not seen in near-term fetuses. In both surviving and nonsurviving preterm fetuses, cardiovascular responses were characterized by decreased arterial pressure, negative T waves, and tachycardia accompanied by an increase in FHRV. Similar changes were not observed in the near-term fetuses after LPS. The study shows that preterm lambs are more sensitive to LPS in terms of myocardial/cardiovascular response than the more mature fetuses are. High FHRV and negative ST waveform seem to characterize the LPS-induced stress response in preterm fetuses.
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| 15. |
- Bosaeus, Marja, et al.
(författare)
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Body Composition During Pregnancy: Longitudinal Changes and Method Comparisons
- 2020
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; :27, s. 1477-1489
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Tidskriftsartikel (refereegranskat)abstract
- The Pregnancy Obesity Nutrition and Child Health study is a longitudinal study of reproductive health. Here we analyzed body composition of normal-weight and obese Swedish women by three methods during each trimester of pregnancy. Cross-sectional and longitudinal fat mass estimates using quantitative magnetic resonance (QMR) and bioelectrical impedance analysis (BIA) (Tanita MC-180MA-III) were compared with fat mass determined by air displacement plethysmography (ADP) in pregnancy weeks 8-12, 24-26, and 35-37 in normal-weight women (n = 122, BMI = 22.1 +/- 1.6 kg/m(2)) and obese women (n = 29, BMI = 34.6 +/- 3.6 kg/m(2)). ADP results were calculated from pregnancy-adjusted fat-free mass densities. Mean fat mass by QMR and ADP were similar in obese women, although with wide limits of agreement. In normal-weight women, QMR overestimated mean fat mass in all trimesters, with systematic overestimation at low fat mass values in trimesters 1 and 3. In obese women, fat mass by BIA was grossly underestimated and imprecise in all trimesters, especially at higher values in trimester 2. In normal-weight women, fat mass by BIA was moderately lower than by ADP in trimester 1, similar in trimester 2, and moderately higher in trimester 3. QMR and ADP assessed fat mass changes similarly in obese women, whereas BIA overestimated fat mass changes in normal-weight women. Mean fat mass and fat mass changes by QMR and pregnancy-adjusted ADP were similar in pregnant obese women. Mean fat mass by QMR and fat mass changes by BIA were higher than corresponding values determined by pregnancy-adjusted ADP in normal-weight women.
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| 16. |
- Callbo, Paliz Nordlof, et al.
(författare)
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Novel Associations Between Mid-Pregnancy Cardiovascular Biomarkers and Preeclampsia: An Explorative Nested Case-Control Study
- 2024
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Ingår i: REPRODUCTIVE SCIENCES. - 1933-7191 .- 1933-7205. ; 31, s. 1391-1400
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Tidskriftsartikel (refereegranskat)abstract
- Prediction of women at high risk of preeclampsia is important for prevention and increased surveillance of the disease. Current prediction models need improvement, particularly with regard to late-onset preeclampsia. Preeclampsia shares pathophysiological entities with cardiovascular disease; thus, cardiovascular biomarkers may contribute to improving prediction models. In this nested case-control study, we explored the predictive importance of mid-pregnancy cardiovascular biomarkers for subsequent preeclampsia. We included healthy women with singleton pregnancies who had donated blood in mid-pregnancy (similar to 18 weeks' gestation). Cases were women with subsequent preeclampsia (n = 296, 10% of whom had early-onset preeclampsia [< 34 weeks]). Controls were women who had healthy pregnancies (n = 333). We collected data on maternal, pregnancy, and infant characteristics from medical records. We used the Olink cardiovascular II panel immunoassay to measure 92 biomarkers in the mid-pregnancy plasma samples. The Boruta algorithm was used to determine the predictive importance of the investigated biomarkers and first-trimester pregnancy characteristics for the development of preeclampsia. The following biomarkers had confirmed associations with early-onset preeclampsia (in descending order of importance): placental growth factor (PlGF), matrix metalloproteinase (MMP-12), lectin-like oxidized LDL receptor 1, carcinoembryonic antigen-related cell adhesion molecule 8, serine protease 27, pro-interleukin-16, and poly (ADP-ribose) polymerase 1. The biomarkers that were associated with late-onset preeclampsia were BNP, MMP-12, alpha-L-iduronidase (IDUA), PlGF, low-affinity immunoglobulin gamma Fc region receptor II-b, and T cell surface glycoprotein. Our results suggest that MMP-12 is a promising novel preeclampsia biomarker. Moreover, BNP and IDUA may be of value in enhancing prediction of late-onset preeclampsia.
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| 17. |
- Campo, S, et al.
(författare)
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Is a positive family history of endometriosis a risk factor for endometrioma recurrence after laparoscopic surgery?
- 2014
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 21:4, s. 526-31
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Tidskriftsartikel (refereegranskat)abstract
- A total of 148 patients were followed up for an average of 30.1 ± 17 months following to laparoscopic excision of ovarian endometriomas by a single surgical team. Bivariate and multivariate analyses were used to investigate the association between endometrioma recurrence and several factors, age, body mass index, family history, cyst diameter, number and location, adhesions or peritoneal implants, occurrence of spillage, postoperative treatment with gonadotropin-releasing hormone agonist, or pregnancies. The overall recurrence rate of the endometriomas was 18.2%. At bivariate analysis, recurrence rate was significantly higher in patients with a positive family history of endometriosis (40% vs 14.8%). Recurrence was also more frequent, albeit nonsignificantly, in patients with a history of dysmenorrhea, intraoperative spillage, and postoperative hormonal suppression. At multivariate analysis with logistic regression, a positive family history of endometriosis was the only variable independently associated with endometrioma recurrence following laparoscopic removal (odds ratio 3.245; 95% confidence interval: 1.090-9.661).Keywords endometrioma, endometriosis, laparoscopy, recurrence, family history
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| 18. |
- Dabo, Fatimah, et al.
(författare)
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Plasma Levels of beta-Endorphin During Pregnancy and Use of Labor Analgesia
- 2010
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 17:8, s. 742-747
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Tidskriftsartikel (refereegranskat)abstract
- beta-endorphins are endogenous opioid substances produced by the pituitary gland and placenta. The aims of this project were to longitudinally follow plasma levels of beta-endorphin during pregnancy in women with a healthy pregnancy and to investigate whether plasma levels of beta-endorphin in late pregnancy are associated with need for additional pain medication beyond nitrous oxide during labor. Plasma samples from 45 women were collected at gestational weeks 10, 25, 28, 33 and 37, and beta-endorphin was analyzed by radioimmunoassay (RIA). Plasma levels of beta-endorphin displayed a significant decrease in gestational weeks 28 and 33 compared to week 10, followed by a subsequent increase between gestational weeks 28 and 37. However, there was no change in levels of beta-endorphin between gestational weeks 10 and 37. Low levels of beta-endorphin at the end of pregnancy were associated with need for additional pain medication beyond nitrous oxide during labor, although the causal relationship is unclear.
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| 19. |
- Dabo Pettersson, Fatimah, 1975-, et al.
(författare)
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The A118G Single Nucleotide Polymorphism of Human μ–Opioid Receptor Gene and Use of Labor Analgesia
- 2012
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 19:9, s. 962-967
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Tidskriftsartikel (refereegranskat)abstract
- The human µ-opioid receptor (MOR) is the major site of action of endogenous opioids and most of the clinically used opioid analgesics. The single-nucleotide polymorphism (SNP), A118G of the MOR 1 gene (OPRM1), has been associated with altered pain perception. The aim of this study was to investigate whether this polymorphism of OPRM1 is associated with a number of pain-related behaviors during labor. In this observational retrospective population-based study, pregnant women (n = 814) were recruited at gestational week 18. A plasma sample was collected from each participant and an SNP genotyping assay was performed. No differences in sociodemographic variables or labor pain-related outcomes, such as stage of cervical dilation on arrival at the delivery unit or use of any type of second-line analgesia during spontaneous labor, were found between noncarriers and G-allele carriers of OPRM1. We conclude that there is no association between the A118G polymorphism of OPRM1 regarding pain-related behavior during labor.
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| 20. |
- Di Gravio, Chiara, et al.
(författare)
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The Association of Maternal Age With Fetal Growth and Newborn Measures : The Mumbai Maternal Nutrition Project (MMNP)
- 2019
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Ingår i: Reproductive Sciences. - : SAGE PUBLICATIONS INC. - 1933-7191 .- 1933-7205. ; 26:7, s. 918-927
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Tidskriftsartikel (refereegranskat)abstract
- Background: Young maternal age is associated with poorer birth outcomes, but the mechanisms are incompletely understood. Using data from a prospective cohort of pregnant women living in Mumbai slums, India, we tested whether lower maternal age was associated with adverse fetal growth.Methods: Fetal crown-rump length (CRL) was recorded at a median (interquartile range, IQR) of 10 weeks' gestation (9-10 weeks). Head circumference (HC), biparietal diameter (BPD), femur length (FL), and abdominal circumference (AC) were recorded at 19 (19-20) and 29 (28-30) weeks. Newborns were measured at a median (IQR) of 2 days (1-3 days) from delivery. Gestation was assessed using prospectively collected menstrual period dates.Results: The sample comprised 1653 singleton fetuses without major congenital abnormalities, of whom 1360 had newborn measurements. Fetuses of younger mothers had smaller CRL (0.01 standard deviation [SD] per year of maternal age; 95% confidence interval CI: 0.00-0.02(1); P = .04), and smaller HC, FL, and AC at subsequent visits. Fetal growth of HC (0.04 cm; 95% CI: 0.02-0.05; P < .001), BPD (0.01 cm; 95% CI: 0.00-0.01; P = .009), FL (0.04 cm; 95% CI: 0.02-0.06; P < .001), and AC (0.01 cm; 95% CI: 0.00-0.01; P = .003) up to the third trimester increased with maternal age. Skinfolds, head, and mid-upper arm circumferences were smaller in newborns of younger mothers. Adjusting for maternal prepregnancy socioeconomic status, body mass index, height, and parity attenuated the associations between maternal age and newborn size but did not change those with fetal biometry.Conclusion: Fetuses of younger mothers were smaller from the first trimester onward and grew slower, independently of known confounding factors.
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| 21. |
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Lindberger, Emelie, et al.
(författare)
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Early Mid-pregnancy Blood-Based Proteins as Possible Biomarkers of Increased Infant Birth Size in Sex-Stratified Analyses
- 2023
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Ingår i: Reproductive Sciences. - : Springer. - 1933-7191 .- 1933-7205. ; 30, s. 1165-1175
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate the associations of 92 maternal blood-based proteins with increased infant birth size. The study was performed at the Uppsala University Hospital, Sweden, and included 857 mother and child dyads. The mean age of the women was 30.3 years, and 53.2% were nulliparous. Blood samples were collected at mean 18 + 2 weeks' gestation, and the Olink cardiovascular II panel was used to measure 92 proteins, either known to be or suspected to be markers of cardiovascular and inflammatory disease in humans. Multiple linear regression models adjusted for maternal age, parity, pre-conception BMI, height, and smoking were performed to evaluate the association of each individual protein with infant birth size. We also performed sex-stratified analyses. Eight proteins (Matrix metalloproteinase-12 (MMP-12), Prostasin (PRSS8), Adrenomedullin (ADM), Pappalysin-1 (PAPP-A), Angiotensin-converting enzyme 2 (ACE2), Sortilin (SORT1), Lectin-like oxidized LDL receptor 1 (LOX-1), and Thrombomodulin (TM)) were associated with infant birth size after false discovery rate adjustment. In the analyses including only female infants, ten proteins (MMP-12, Growth/differentiation factor 2 (GDF-2), PRSS8, SORT1, ADM, Interleukin-1 receptor antagonist protein (IL-1ra), Leptin (LEP), ACE2, TM, and Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A)) were associated with infant birth size. Two proteins (PAPP-A and PRSS8) were associated with infant birth size among male infants. Our study suggests several proteins as potential biomarkers for increased birth weight, and our findings could act as a base for future research to identify new potential markers that could be added to improve screening for large infants.
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| 29. |
- Lindberger, Emelie, et al.
(författare)
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Maternal blood-based protein biomarkers in relation to abdominal fat distribution measured by ultrasound in early mid-pregnancy
- 2022
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Ingår i: Reproductive Sciences. - : Springer Nature. - 1933-7191 .- 1933-7205. ; 29:8, s. 2333-2341
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to examine the associations of early mid-pregnancy ultrasound measured visceral and subcutaneous fat depths with blood-based protein biomarkers. This was a cross-sectional study including 201 pregnant women at Uppsala University Hospital, Sweden. The mean age of the women was 31.0 years, and 57.7% were nulliparous. Maternal visceral and subcutaneous fat depths were measured by ultrasound at the early second-trimester anomaly scan. A non-fasting blood sample was collected in conjunction with the second-trimester anomaly scan, and the Olink cardiovascular II panel was used to measure 92 blood-based protein biomarkers in the sample. Cross-sectional associations of visceral and subcutaneous fat depths with blood-based protein biomarkers were examined using Mann–Whitney U tests with false discovery rate adjustments. In addition, linear regression analyses adjusting for maternal age, parity, and early pregnancy body mass index were performed. The results showed differences in one biomarker between women with elevated (≥ 52 mm) versus normal (< 52 mm) visceral fat depth, and in three biomarkers between women with elevated (≥ 22 mm) versus normal (< 22 mm) subcutaneous fat depth. Hence, levels of blood-based protein biomarkers differ between pregnant women with dissimilar body fat distributions, which might reflect disparities in biological pathways.
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| 30. |
- Moberg, Christian, et al.
(författare)
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VEGF-A and Serum Withdrawal Induced Changes in the Transcript Profile in Human Endometrial Endothelial Cells
- 2010
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 17:6, s. 590-611
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Tidskriftsartikel (refereegranskat)abstract
- The changes in transcript profile induced by vascular endothelial growth factor (VEGF-A) and serum withdrawal in primary human endometrial endothelial cells (ECs) were investigated using microarrays, gene ontology and pathway analysis. Vascular endothelial growth factor A altered the levels of transcripts involved in angiogenesis, cell survival, and apoptosis, including up-and downregulation of AKT1, BAD, MIF, and IGFBP3 and ANGPT2, respectively. Serum deprivation induced downregulation of cell-cycle-related transcripts such as mitosis regulators CDC20 and SPC25. Of the transcripts regulated by both VEGF-A and partial serum deprivation, remarkably 88 of 89 showed reciprocal regulation (p < 1 x 10(-49)). These are predominantly cell-fate-associated transcripts and this novel observation suggests that endometrial ECs may be particularly dependant on the levels of these transcripts. Our results show that in addition to the known role of VEGF-A as an EC growth and survival promoter, it also regulates apoptosis-related messenger RNAs (mRNAs), many of which were reciprocally regulated following serum withdrawal.
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| 31. |
- Myatt, Leslie, et al.
(författare)
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A standardized template for clinical studies in preterm birth.
- 2012
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Ingår i: Reproductive sciences (Thousand Oaks, Calif.). - : Springer Science and Business Media LLC. - 1933-7205 .- 1933-7191. ; 19:5, s. 474-82
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Tidskriftsartikel (refereegranskat)abstract
- Preterm birth is a major societal and economic problem accounting for 80 to 90% of neonatal morbidity and mortality worldwide. It is recognized as a complex multifactorial condition comprising several distinct clinical phenotypes with different underlying etiologies. As animal models are expensive and fail to mimic the biology of spontaneous preterm birth in humans, understanding the pathophysiology requires detailed clinical studies. Meta-analyses and clinical translation of data, however, are limited by heterogeneity of study design and size, publication and reporting biases, definition of patient groups, and a lack of standard universal definitions. This article provides a harmonized open-source template for designing clinical studies addressing preterm birth.
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| 32. |
- Nordqvist, Sarah, 1962-, et al.
(författare)
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The Presence of Histidine-Rich Glycoprotein in the Female Reproductive Tract and in Embryos
- 2010
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 17:10, s. 941-947
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Tidskriftsartikel (refereegranskat)abstract
- A well-regulated angiogenesis is crucial for proper embryo implantation, embryogenesis, and pregnancy development. Monitoring the presence and distribution of angiogenic regulators in the female reproductive tract and in the early embryo is important for a broader understanding of the molecular aspects of fertility, embryogenesis, and pregnancy. Histidine-rich glycoprotein (HRG) is a glycoprotein involved in angiogenesis. Its presence in the female reproductive tract or in embryos has not previously been studied. Follicular fluid, culture medium, and embryos were obtained from patients undergoing in vitro fertilization (IVF). Biopsies from inner genitalia and placenta were collected at surgery. Histidine-rich glycoprotein presence was investigated by immunohistochemistry and Western blot. Polymerase chain reaction (PCR) was used to determine HRG expression in tissues or by embryos. We identified HRG in follicular fluid, the female reproductive tract, and placenta, as well as in the embryos. Moreover, HRG expression was observed in blastocysts. Thus, the angiogenic properties of HRG might affect fertility.
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| 35. |
- Roberts, J. M., et al.
(författare)
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Vision for Improving Pregnancy Health: Innovation and the Future of Pregnancy Research
- 2022
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 29:10, s. 2908-2920
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Tidskriftsartikel (refereegranskat)abstract
- Understanding, predicting, and preventing pregnancy disorders have been a major research target. Nonetheless, the lack of progress is illustrated by research results related to preeclampsia and other hypertensive pregnancy disorders. These remain a major cause of maternal and infant mortality worldwide. There is a general consensus that the rate of progress toward understanding pregnancy disorders lags behind progress in other aspects of human health. In this presentation, we advance an explanation for this failure and suggest solutions. We propose that progress has been impeded by narrowly focused research training and limited imagination and innovation, resulting in the failure to think beyond conventional research approaches and analytical strategies. Investigations have been largely limited to hypothesis-generating approaches constrained by attempts to force poorly defined complex disorders into a single "unifying" hypothesis. Future progress could be accelerated by rethinking this approach. We advise taking advantage of innovative approaches that will generate new research strategies for investigating pregnancy abnormalities. Studies should begin before conception, assessing pregnancy longitudinally, before, during, and after pregnancy. Pregnancy disorders should be defined by pathophysiology rather than phenotype, and state of the art agnostic assessment of data should be adopted to generate new ideas. Taking advantage of new approaches mandates emphasizing innovation, inclusion of large datasets, and use of state of the art experimental and analytical techniques. A revolution in understanding pregnancy-associated disorders will depend on networks of scientists who are driven by an intense biological curiosity, a team spirit, and the tools to make new discoveries.
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| 36. |
- Somasundaram, Dinesh Babu, et al.
(författare)
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Lactational Exposure to Di (2-ethylhexyl) Phthalate Impairs the Ovarian and Uterine Function of Adult Offspring Rat.
- 2015
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205.
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Tidskriftsartikel (refereegranskat)abstract
- Phthalates, a class of chemicals used as plasticizers, are economically important due to several industrial applications. Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used phthalate plasticizer, and it has been described as a potent antiandrogen in males. In this study, lactating dams were exposed via oral gavage to corn oil (vehicle) and DEHP (1, 10, and 100 mg/kg body weight) from postnatal day 1 to 21, and the effects were evaluated in the ovary and uterus of F1 progeny. DEHP exposure significantly decreased the body weight and organ weight in a dose-dependent manner. Serum levels of estradiol, testosterone, and progesterone were decreased but anogenital distance was unaffected. The mRNA expressions of luteinizing hormone receptor, follicle-stimulating hormone receptor, androgen receptor, estrogen receptor (ERα and ERβ), progesterone receptor, peroxisome proliferator-activated receptor γ, 3β hydroxysteroid dehydrogenase, aromatase, and steroidogenic acute regulatory protein were altered in the ovary of F1 progeny rats. Our finding suggest that lactational exposure to DEHP has transgenerational effect on female reproductive system.
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| 37. |
- Svensson, Agnes, et al.
(författare)
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Associations Between Endometriosis and Gut Microbiota
- 2021
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 28:8, s. 2367-2377
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota has been associated with many diseases, including endometriosis. However, very few studies have been conducted on this topic in human. This study aimed to investigate the association between endometriosis and gut microbiota. Women with endometriosis (N=66) were identified at the Department of Gynaecology and each patient was matched with three controls (N=198) from the general population. All participants answered questionnaires about socioeconomic data, medical history, and gastrointestinal symptoms and passed stool samples. Gut bacteria were analyzed using 16S ribosomal RNA sequencing, and in total, 58 bacteria were observed at genus level in both patients with endometriosis and controls. Comparisons of the microbiota between patients and controls and within the endometriosis cohort were performed. Both alpha and beta diversities were higher in controls than in patients. With the false discovery rate q<0.05, abundance of 12 bacteria belonging to the classes Bacilli, Bacteroidia, Clostridia, Coriobacteriia, and Gammaproteobacter differed significantly between patients and controls. Differences observed between patients with or without isolated ovarian endometriosis, involvement of the gastrointestinal tract, gastrointestinal symptoms, or hormonal treatment disappeared after calculation with false discovery rate. These findings indicate that the gut microbiota may be altered in endometriosis patients.
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| 38. |
- Sverremark-Ekström, Eva
(författare)
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Division of cytokines into TH1/TH2 : a word of caution.
- 2010
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Ingår i: Reproductive sciences (Thousand Oaks, Calif.). - : Springer Science and Business Media LLC. - 1933-7205 .- 1933-7191. ; 17:4, s. 318-9
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Tidskriftsartikel (refereegranskat)
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| 39. |
- Viklund, Felicia, et al.
(författare)
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Protein Concentrations of Thrombospondin-1, MIP-1β, and S100A8 Suggest the Reflection of a Pregnancy Clock in Mid-Trimester Amniotic Fluid
- 2020
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7205 .- 1933-7191. ; 27:12, s. 2146-2157
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Tidskriftsartikel (refereegranskat)abstract
- The development of immunoassays enables more sophisticated studies of the associations between protein concentrations and pregnancy outcomes, allowing early biomarker identification that can improve neonatal outcomes. The aim of this study was to explore associations between selected mid-trimester amniotic fluid proteins and (1) overall gestational duration and (2) spontaneous preterm delivery. A prospective cohort study, including women undergoing mid-trimester transabdominal genetic amniocentesis, was performed in Gothenburg, Sweden, 2008–2016 (n = 1072). A panel of 27 proteins related to inflammation was analyzed using Meso-Scale multiplex technology. Concentrations were adjusted for gestational age at sampling, experimental factors, year of sampling, and covariates (maternal age at sampling, parity (nulliparous/multiparous), smoking at first prenatal visit, and in vitro fertilization). Cox regression analysis of the entire cohort was performed to explore possible associations between protein concentrations and gestational duration. This was followed by Cox regression analysis censored at 259 days or longer, to investigate whether associations were detectable in women with spontaneous preterm delivery (n = 47). Finally, linear regression models were performed to analyze associations between protein concentrations and gestational duration in women with spontaneous onset of labor at term (n = 784). HMG-1, IGFBP-1, IL-18, MIP-1α, MIP-1β, S100A8, and thrombospondin-1 were significantly associated with gestational duration at term, but not preterm. Increased concentrations of thrombospondin-1, MIP-1β, and S100A8, respectively, were significantly associated with decreased gestational duration after the Holm-Bonferroni correction in women with spontaneous onset of labor at term. This adds to the concept of a pregnancy clock, where our findings suggest that such a clock is also reflected in the amniotic fluid at early mid-trimester, but further research is needed to confirm this.
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| 40. |
- Wickström, Karin, et al.
(författare)
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Effect of Lignocaine on IL-6, IL-8, and MCP-1 in Peritoneal Macrophages and Endometriotic Stromal Cells
- 2017
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Ingår i: Reproductive Sciences. - : SAGE PUBLICATIONS INC. - 1933-7191 .- 1933-7205. ; 24:3, s. 382-392
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The objective was to evaluate the effect of lignocaine on cytokine expression and secretion in vitro in peritoneal fluid macrophages and endometriotic stromal cells. Design: Experimental in vitro study on human cells. Population and Sample: Peritoneal fluid (n = 10) and samples from endometriotic cysts (n = 7) were collected from 13 women (women with endometriosis n = 8, and healthy controls n = 5) during surgery for clinical reasons. Methods: Macrophages from the peritoneal fluid and cells from the inside of the endometriotic cysts capsules were isolated and cultivated for 24 to 48 hours in medium with and without the supplement of lignocaine 0.1 or 1.0 mg/mL. Relative gene expression of monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), and IL-8 was evaluated with quantitative polymerase chain reaction and compared between treated and untreated cells with Wilcoxon matched pairs. The concentrations of MCP-1, IL-6, and IL-8 were measured using enzyme-linked immunosorbent assay and were compared between treated and untreated cells with Wilcoxon matched pairs. Results: The gene expression and protein secretion of IL-8 in endometriotic stromal cells after incubation with lignocaine 0.1 mg/mL were significantly decreased after 24 hours compared to the controls (P =.028 and P =.018). Macrophages from healthy controls had a significant lower gene expression of all tested cytokines (P =.043) after treatment with lignocaine, but there were no significant differences in protein level. Macrophages from women with endometriosis showed diverging results since 3 of 5 samples showed increased gene expression of 1 (n = 2) or 2 cytokines (n = 1) after lignocaine treatment. Conclusion: Lignocaine can affect the gene expression and secretion of some proinflammatory cytokines in vitro.
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| 41. |
- Wikström, Anna-Karin, et al.
(författare)
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Increased circulating levels of the antiangiogenic factor endostatin in early-onset but not late-onset preeclampsia
- 2009
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 16:10, s. 995-1000
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Tidskriftsartikel (refereegranskat)abstract
- Changes in circulating angiogenic factors seem to play a key role in the pathogenesis of preeclampsia and it seems as if these changes are of greater importance in the pathogenesis of early-onset than of late-onset disease. Endostatin is a potent, broad spectrum antagonist of angiogenesis whose role in preeclampsia is poorly investigated. The aim of this study was to estimate whether circulating endostatin levels are altered in preeclampsia, and whether women with early-onset (before 32 weeks of gestation; n = 16) and late-onset (after 35 weeks of gestation; n = 19) preeclampsia differ in this regard. Women with early-onset, but not of late-onset preeclampsia had higher levels of endostatin than healthy pregnant women in corresponding lengths of gestation. The results of the study support the hypothesis that there is heterogeneity between early- and late-onset preeclampsia, with a stronger association between an altered angiogenic balance and early-onset than late-onset disease.
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