Marcus Sjödin - Academia.edu (original) (raw)

Papers by Marcus Sjödin

Journal of Assisted Reproduction and Genetics, Jul 15, 2020

PurposeOur purpose was to identify human ovarian extracellular matrix (ECM) components that would... more PurposeOur purpose was to identify human ovarian extracellular matrix (ECM) components that would support in vitro culture of human ovarian tissue and be compatible with possible future clinical applications. We characterized ovarian expression of laminins and selected three laminin tripeptides for culture experiments to be compared with Matrigel, an undefined and animal-based mixture of ECM components.MethodsExpression of the 12 laminin genes was determined on transcript and protein levels using cortical tissue samples (n = 6), commercial ovary RNA (n = 1), follicular fluid granulosa cells (n = 20), and single-cell RNA-sequencing data. Laminin 221 (LN221), LN521, LN511, and their mixture were chosen for a 7-day culture experiment along with Matrigel using tissue from 17 patients. At the end of the culture, follicles were evaluated by scoring and counting from serial tissue sections, apoptosis measured using in situ TUNEL assay, proliferation by Ki67 staining, and endocrine function by quantifying steroids in culture media using UPLC-MS/MS.ResultsApproximately half of the cells in ovarian cortex expressed at least one laminin gene. The overall most expressed laminin α-chains were LAMA2 and LAMA5, β-chains LAMB1 and LAMB2, and γ-chain LAMC1. In culture experiments, LN221 enhanced follicular survival compared with Matrigel (p < 0.001), whereas tissue cultured on LN521 had higher proportion of secondary follicles (p < 0.001). LN511 and mixture of laminins did not support the cultures leading to lower follicle densities and higher apoptosis. All cultures produced steroids and contained proliferating cells.ConclusionsLN221 and LN521 show promise in providing xeno-free growth substrates for human ovarian tissue cultures, which may help in further development of folliculogenesis in vitro for clinical practices. The system could also be used for identification of adverse effects of chemicals in ovaries.Electronic supplementary materialThe online version of this article (10.1007/s10815-020-01886-4) contains supplementary material, which is available to authorized users.

Toxicology and Applied Pharmacology, 2018

Resveratrol supports and alpha-naphthoflavone disrupts growth of human ovarian follicles in an in... more Resveratrol supports and alpha-naphthoflavone disrupts growth of human ovarian follicles in an in vitro tissue culture model

Environmental Science & Technology, Mar 7, 2019

Perfluorinated alkyl acids (PFAA) are highly persistent and bioaccumulative and have been associa... more Perfluorinated alkyl acids (PFAA) are highly persistent and bioaccumulative and have been associated with several adverse health effects. The chemical structure mainly differs in two ways: the length of the hydrophobic alkyl chain and the type of hydrophilic end group. Little is known how the chemical structure affects the toxicokinetics (TK) in different organisms. We studied the TK of four PFAA (PFOS, PFHxS, PFOA, and PFBA) with different chain lengths (4−8 carbons) and functional groups (sulfonic and carboxylic acid) in zebrafish (Danio rerio) embryo. The time courses of the external (ambient water) and internal concentrations were determined at three exposure concentrations from 2 up to 120 h postfertilization (hpf). Three of the four PFAA showed a biphasic uptake pattern with slow uptake before hatching (around 48 hpf) and faster uptake thereafter. A two-compartment TK model adequately described the biphasic uptake pattern, suggesting that the chorion functions as an uptake barrier until 48 hpf. The bioconcentration factors (BCF) determined at 120 hpf varied widely between PFAA with averages of approximately 4000 (PFOS), 200 (PFHxS), 50 (PFOA), and 0.8 (PFBA) L kg dry weight −1 , suggesting that both the alkyl chain length and the functional group influence the TK. The differences in toxic potency were reduced by 3 orders of magnitude when comparing internal effect concentrations instead of effective external concentrations.

Human Reproduction, Apr 13, 2020

Medicine and Pharmacy Reports, Oct 30, 2017

Background and aims. Selective serotonin reuptake inhibitors (SSRIs) are antidepressants increasi... more Background and aims. Selective serotonin reuptake inhibitors (SSRIs) are antidepressants increasingly prescribed against depression during and after pregnancy. However, these compounds cross the placenta and are found in breast milk, thus reaching, and possibly affecting, the fetus and infant during critical developmental stages. Fluoxetine (FLX), a widely used SSRI, can interfere with estrogen signaling, which is important for the development of female sex organs and certain brain areas, among others. Interference with estrogen signaling can take place on different levels, e.g., by affecting receptor activity or hormone levels. FLX has previously been shown to induce estrogen receptor-dependent transcription in vitro at high concentrations. In this study we set out to assess effects of FLX on estradiol levels in vitro. Methods. FLX was tested using the OECD recommended H295R model, a human adrenocortical carcinoma cell line that is able to produce all steroid hormones found in the gonads and adrenal glands, including estradiol and testosterone. H295R cells were incubated with different doses of FLX for 48h. Subsequently, concentrations of these two steroids were measured in cell culture medium after FLX exposure, using liquid chromatography coupled with tandem mass spectrometry. Aromatase mRNA expression was assessed using qPCR. Results. Fluoxetine significantly increased estradiol secretion in H295R cells after a 48h exposure at low, submicromolar concentrations, but showed no effects on testosterone levels or aromatase mRNA expression. Conclusion. Fluoxetine has the potential to interfere with estrogenic signaling by increasing estradiol secretion at low concentrations, which are relevant for fetal and adult human exposure.

Human Reproduction, Aug 14, 2019

STUDY QUESTION: Does first-line chemotherapy affect the quality of ovarian pre-antral follicles a... more STUDY QUESTION: Does first-line chemotherapy affect the quality of ovarian pre-antral follicles and stromal tissue in a population of young patients? SUMMARY ANSWER: Exposure to first-line chemotherapy significantly impacts follicle viability, size of residual intact follicles, steroid secretion in culture and quality of the stromal compartment. WHAT IS KNOWN ALREADY: First-line chemotherapy is considered to have a low gonadotoxic potential, and as such, does not represent an indication for fertility preservation. Studies investigating the effects of chemotherapy on the quality of ovarian tissue stored for fertility preservation in young patients are limited and the results sometimes contradictory. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study including young patients referred to three centers (Helsinki, Oslo and Tampere) to perform ovarian tissue cryopreservation for fertility preservation between 2003 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 43 patients (age 1-24 years) were included in the study. A total of 25 were exposed to first-line chemotherapy before cryopreservation, whereas 18 patients were not. Density and size of follicles divided by developmental stages, prevalence of atretic follicles, health of the stromal compartment and functionality of the tissue in culture were evaluated and related to age and chemotherapy exposure. Activation of dormant follicles and DNA damage were also assessed. MAIN RESULTS AND THE ROLE OF CHANCE: Patients exposed to first-line chemotherapy showed a significantly higher density of atretic primordial and intermediary follicles than untreated patients. The intact primordial and intermediary follicles were significantly smaller in size in patients exposed to chemotherapy. Production of steroids in culture was also significantly impaired and a higher content of collagen and DNA damage was observed in the stromal compartment of treated patients. Collectively, these observations may indicate reduced quality and developmental capacity of follicles as a consequence of first-line chemotherapy exposure. Neither increased activation of dormant follicles nor elevated levels of DNA damage in oocyte nuclei were found in patients exposed to chemotherapy.

Journal of Proteome Research, Jul 21, 2010

In this study, temperature-induced phase fractionation also known as cloud-point extraction (CPE)... more In this study, temperature-induced phase fractionation also known as cloud-point extraction (CPE) with the nonionic surfactant Triton X-114 was used to simultaneously extract hydrophobic and hydrophilic proteins from porcine brain tissue. Various protein precipitation/delipidation procedures were investigated to efficiently remove lipids and detergents while retaining maximum protein recoveries. The best performing delipidation method was then used in combination with CPE to compare three different mass spectrometry (MS) based &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;bottom-up&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; proteomic approaches for protein analysis of the porcine brain. In the first approach, the intact proteins were initially separated by one-dimensional (1D) gel electrophoresis. The excised protein bands were digested with trypsin, and the peptides were separated by reversed phase nanoliquid chromatography (RP-nanoLC) followed by electrospray ionization (ESI) tandem mass spectrometry (MS/MS) analysis. The other bottom-up proteomic approaches were based on first enzymatical digestion of the proteins followed by RP-nanoLC separation in combination with matrix assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) or on the combination of in-solution isoelectric focusing (IEF) with ESI-nanoLC-MS/MS of the IEF separated peptides. In total, we found and unambiguously identified 331 unique proteins. The overlap between different techniques was about 10%, showing that the use of multiple proteomic approaches is beneficial to yield a better coverage of the proteome. Furthermore, the overlap between the CPE extracted hydrophilic and hydrophobic proteins was rather small (9-16%), indicating an efficient sample preparation technique to extract and separate hydrophilic and hydrophobic proteins from brain tissue. The percentage of identified membrane proteins was 27%, which is in accordance to the fact that about one-third of all genes in various organisms encode for this class of proteins. The results indicate that cloud point extraction is a promising sample preparation tool, which allows simultaneous in depth studies of brain derived membrane proteins as well as hydrophilic proteins. This technique can be very useful when studying human central nervous system (CNS) tissue or animal models of neurological diseases.

European Respiratory Journal, 2015

Background: COPD is a leading cause of mortality and morbidity; however, the role of inflammatory... more Background: COPD is a leading cause of mortality and morbidity; however, the role of inflammatory mediators in its pathobiology remains unclear. Aim: To investigate the influence of gender in COPD on lipid mediators levels in the bronchoalveolar compartment and serum. Methods: Bronchoalveolar lavage fluid (BALF) and serum were obtained from healthy never-smokers, smokers with normal lung function, and COPD patients (GOLD I-II/A-B) (n=114). Ninety-four lipid mediators derived from the cytochrome P450, lipoxygenase, and cyclooxygenase pathways were analyzed by liquid chromatography-mass spectrometry. Results: Multivariate modeling identified a 9-lipid panel in BALF that classified female smokers with COPD from healthy female smokers (p=6x10-6). No differences were observed for the corresponding male population (p=1.0). Findings were replicated in an independent cohort with 92% accuracy (p=0.005). The strongest drivers were the cytochrome P450-derived epoxide products of linoleic acid (leukotoxins) and their corresponding soluble epoxide hydrolase (sEH)-derived products (leukotoxin-diols). These lipids correlated with lung function in the female COPD group (r=0.87; p=0.0009), as well as mRNA levels of enzymes involved in their biosynthesis (r=0.96; p=0.003). Leukotoxin levels correlated with goblet cell abundance in female COPD patients (r=0.72; p=0.028). Conclusions: Findings suggest a mechanism by which goblet cell-associated cytochrome P4509s in combination with sEH activity produce elevated leukotoxin-diol levels, which play a putative role in the clinical manifestations of COPD in a female-dominated disease sub-phenotype. Data support the inhibition of sEH as a therapeutic target for treatment of COPD.

Table S6. Results of the Cochran-Armitage test with radiography stage in sphingolipids significan... more Table S6. Results of the Cochran-Armitage test with radiography stage in sphingolipids significantly differing (p

Table S5. Spearman's correlations between lipid mediators and age for healthy controls and pa... more Table S5. Spearman's correlations between lipid mediators and age for healthy controls and patients with sarcoidosis. Compounds with p

Table S4. Results for the comparisons of lipid mediator levels between healthy (n = 16) and sarco... more Table S4. Results for the comparisons of lipid mediator levels between healthy (n = 16) and sarcoidosis (n = 41) groups. Values have been normalized to the median value of the healthy group. Compounds with p

Appendix S1. Detailed procedures employed for the extraction of eicosanoids, endocannabinoids and... more Appendix S1. Detailed procedures employed for the extraction of eicosanoids, endocannabinoids and sphingolipids. (PDF 11 kb)

Table S3. Internal standards for each of the three LC-MS/MS lipid mediator platforms. (PDF 78 kb)

Table S2. Nomenclature for the compounds screened in the samples. Compounds reproducibly detected... more Table S2. Nomenclature for the compounds screened in the samples. Compounds reproducibly detected in samples and submitted to data analysis are highlighted in bold. (DOCX 196 kb)

Data S1. Summary of data used in the analysis. (XLSX 31 kb)

Appendix S2. Chromatographic and general MS conditions employed in the detection of eicosanoids, ... more Appendix S2. Chromatographic and general MS conditions employed in the detection of eicosanoids, sphingolipids and endocannabinoids. (PDF 97 kb)

European Respiratory Journal, 2014

Background: We tested if lipid mediator profiles could be used as biomarkers of certain phenotype... more Background: We tested if lipid mediator profiles could be used as biomarkers of certain phenotypes of asthma and measured the urinary concentrations of metabolites of the cysteinyl-leukotrienes (CysLTs), prostaglandins (PGs) and isoprostanes (IPs) at the cross-sectional baseline visit in the U-BIOPRED study of adults with asthma. Methods: Subjects (aged 18-79) with severe asthma (SA; n=231), mild-to-moderate asthma (MA; n=71) and healthy controls (HC; n=72) provided spot urine samples that were analysed using UPLC-MS/MS (Balgoma et al Anal Chem 2013). Results: The urinary excretion of all lipid mediators, except tetranorPGEM, were highest among SA, and generally higher in MA vs. healthy controls. LTE 4 displayed the highest median fold change (MFC) (MFC=2.1, P 2α (MFC=1.6, P 2α (MFC=1.3, P 4 >and tetranorPGDM. The subjects with the highest 25 th percentile of urinary LTE 4 had a highly significant lower lung function than those in the lowest 25 th percentile (FEV 1 % predicted be...

Mapping the protein distribution within a microdialysis sampling system by on-surface enzymatic d... more Mapping the protein distribution within a microdialysis sampling system by on-surface enzymatic digestion in combination with mass spectrometry

Analytical Strategies for Protein Biomarker Discovery in the Central Nervous System using Mass Sp... more Analytical Strategies for Protein Biomarker Discovery in the Central Nervous System using Mass Spectrometry

Spinal cord stimulation (SCS) is a widely used mode of therapy in neuropathic pain of peripheral ... more Spinal cord stimulation (SCS) is a widely used mode of therapy in neuropathic pain of peripheral origin. Despite its well-established clinical use, the underlying physiological mechanisms behind th ...