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  • 1.
    Kumaresan, Arumugam
    et al.
    Swedish Univ Agr Sci, Div Reprod, Dept Clin Sci, Uppsala, Sweden.;Natl Dairy Res Inst, Theriogenol Lab, Anim Reprod Gynaecol & Obstet, Karnal, Haryana, India..
    Johannisson, Anders
    Swedish Univ Agr Sci, Div Reprod, Dept Clin Sci, Uppsala, Sweden..
    Nordqvist, Sarah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Kårehed, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Lindgren, Karin E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Morrell, Jane M.
    Swedish Univ Agr Sci, Div Reprod, Dept Clin Sci, Uppsala, Sweden..
    Relationship of DNA integrity to HRG C633T SNP and ART outcome in infertile couples2017In: Reproduction, ISSN 1470-1626, E-ISSN 1476-3990, Vol. 153, no 6, p. 865-876Article in journal (Refereed)
    Abstract [en]

    The status of sperm DNA fragmentation, protamine deficiency, free thiols and disulphide bonds in colloid-selected samples and its relationship to ART outcome or HRG C633T SNP is not known. The objective of this study was to determine these relationships in spermatozoa from men with male factor or unknown factor infertility (n=118) undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Sperm DNA integrity was analysed by flow cytometry using three fluorescent probes (acridine orange, monobromobimane and chromomycin A3). Principal component analysis (PCA) was used to identify the parameters that most influenced fertility. The relationships of sperm DNA integrity with seminal parameters, HRG C633T SNP and ART outcome were established using ANOVA and t-test. Sperm concentration and yield after preparation accounted for 27% of the total variance; sperm DNA integrity (% DFI and disulphide bonds) accounted for 16% of the variance in men from infertile couples. Sperm % DFI was significantly higher (P < 0.05) in older men than in younger men. A significant difference (P < 0.01) was observed in % DFI between smokers and non-smokers. Sperm % DFI was significantly higher (P < 0.01) in male factor infertility compared to either female factor or unknown factor infertility while free thiols were significantly higher (P < 0.01) in unknown infertility factor. No significant difference was observed between IVF success/failure in any of the seminal parameters studied. There was a tendency for protamine deficiency to be higher and disulphide concentration to be lower in men with HRG 633T. Such assessments may provide additional useful information about the prognosis for ART outcome, although more research is needed before clinical guidelines can be provided.

  • 2.
    Kårehed, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Olsson, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Fibrinogen and histidine-rich glycoprotein in early-onset preeclampsia2010In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 89, no 1, p. 131-139Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine whether plasma levels of fibrinogen and the placental tissue distributions of fibrinogen and histidine-rich glycoprotein (HRG) differ between early- and late-onset preeclampsia. DESIGN: The study comprised 18 women with early-onset (gestational weeks 24-32) and 19 women with late-onset (gestational weeks 35-42) preeclampsia. As controls concerning the plasma levels of fibrinogen, we used samples from non-pregnant fertile women, healthy pregnant women at gestational weeks 24-32 and healthy pregnant women at gestational weeks 35-42. Placental samples from women with healthy pregnancies at gestational weeks 35-42 served as controls in the immunohistochemical staining. SETTING: Uppsala University Hospital, Uppsala. METHODS: Plasma fibrinogen levels were analyzed and the placental tissue expression of fibrinogen and HRG determined by immunohistochemistry. RESULTS: Plasma level of fibrinogen was increased in early-onset, but not late-onset, preeclampsia. Levels of fibrinogen were significantly lower, and that of HRG significantly higher, in placentas from women with early-onset preeclampsia as compared with control placentas (p = 0.01 and 0.001). CONCLUSIONS: HRG and fibrinogen might be involved in the hypercoagulability and the angiogenic imbalance seen in early-onset preeclampsia.

  • 3.
    Lindgren, Karin E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hreinsson, Julius
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. IVF Sweden.
    Helmestam, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Wånggren, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Poromaa, Inger Sundström
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kårehed, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Histidine-rich glycoprotein derived peptides affect endometrial angiogenesis in vitro but has no effect on embryo development2016In: Systems biology in reproductive medicine, ISSN 1939-6376, Vol. 62, no 3, p. 192-200Article in journal (Refereed)
    Abstract [en]

    Histidine-rich glycoprotein (HRG) is an abundant plasma protein involved in multiple biological processes including immunology, vascularisation, and coagulation. These processes are of importance in regulating embryo development and implantation. A specific polymorphism in the HRG gene, HRG C633T, has an impact on various aspects of fertility, such as oocyte quality, endometrial receptivity, and possibly the capacity of the embryo itself to implant. To further examine the potential role of the HRG C633T polymorphism in regulating endometrial angiogenesis and on embryo development, two HRG peptides were constructed. These HRG peptides correspond to the amino acids 169-203 of the protein which, in turn, reflects the C633T polymorphism in the gene. The HRG proline or serine peptides were added to cultures of primary human endometrial endothelial (HEE) cells and to human embryos in vitro. The HRG peptides inhibited vascular endothelial growth factor (VEGF) induced proliferation and migration and promoted tube formation of HEE cells. The embryos were monitored using a time-lapse system (EmbryoScope®). Except for a prolonged time from first cleavage after thawing to development of the morula, no difference in embryo morphokinetics or embryo quality was noted in human embryos cultured in the presence of the HRG proline peptide. Taken together, these results suggest that treatment with a specific HRG peptide might prime the endometrium for implantation and be beneficial for adequate placentation. However, addition of a specific HRG proline peptide to human embryos has no beneficial effects in terms of embryo development.

    ABBREVIATIONS: HRG: histidine-rich glycoprotein; HEE: human endometrial endothelial; VEGF: vascular endothelial growth factor; TSP: thrombospondin; SNP; single nucleotide polymorphism; IVF: in vitro fertilization; CLESH-1: CD36 LIMPII Emp structural homology domain-1; ECM: endothelial cell medium; FBS: fetal bovine serum; cDNA: complementary DNA.

  • 4.
    Lindgren, Karin E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kårehed, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Karypidis, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hosseini, Frida
    Department of Clinical Sciences, Division of Obstetrics and Gynaecology, Karolinska Institute, Danderyd Hospital.
    Bremme, Katarina
    Department of Women′s and Children′s Health, Karolinska Institute.
    Landgren, Britt-Marie
    Department of Clinical Sciences, Intervention and Technology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Skjoldebrand-Sparre, Lottie
    Department of Clinical Sciences, Division of Obstetrics and Gynaecology, Karolinska Institute, Danderyd Hospital.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Histidine-rich glycoprotein gene polymorphism in patients with recurrent miscarriage2013In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 8, p. 974-977Article in journal (Refereed)
    Abstract [en]

    Association between the histidine-rich glycoprotein (HRG) C633T single nucleotide polymorphism (SNP) and recurrent miscarriage was investigated in a case-control study. The cases constituted 187 women with recurrent miscarriage that were compared with 395 controls who had delivered a child and had no history of miscarriage. Blood samples were collected from each woman, genomic DNA was extracted and genotyped for the HRG C633T SNP. In the whole study population, the percentage of miscarriage was the same, regardless of genotype (C/C 31.2%, C/T 32.9% and T/T 32.5%). However, an association between homozygous T/T carriers and recurrent miscarriage was detected in a subgroup of women with primary recurrent miscarriage (odds ratio 2.44, 95% CI 1.01-5.92). Our results indicate an important role for the HRG C633T SNP in the occurrence of recurrent miscarriage.

  • 5.
    Lindgren, Karin E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Nordqvist, Sarah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Fertilitetscentrum, Storangsvagen 10, SE-11542 Stockholm, Sweden.; Carl von Linne Clin, Uppsala Sci Pk, SE-75183 Uppsala, Sweden.
    Kårehed, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    The effect of a specific histidine-rich glycoprotein polymorphism on male infertility and semen parameters.2016In: Reproductive BioMedicine Online, ISSN 1472-6483, E-ISSN 1472-6491, Vol. 33, no 2, p. 180-188Article in journal (Refereed)
    Abstract [en]

    In women, there is evidence that a single nucleotide polymorphism (SNP) in the histidine-rich glycoprotein (HRG) named HRG C633T is relevant for a number of fertility outcomes including recurrent miscarriage, ovarian response and pregnancy outcome after IVF. This case-control study was designed to investigate whether the HRG C633T SNP is important for male infertility and pregnancy rate following IVF. Cases were 139 infertile couples and controls were 196 pregnant couples. The 335 couples all contributed with one blood sample per partner. Genomic DNA was extracted and genotyping was performed using a TaqMan® SNP Genotyping Assay. Information on pregnancy rate and semen parameters was derived from medical records. Infertile couples in which the male partner was a homozygous carrier of the HRG C633T SNP had significantly lower (P < 0.01) pregnancy rate following IVF in comparison with couples where the male partner was a heterozygous HRG C633T SNP carrier. Male homozygous HRG 633T SNP carriers had overall lower total sperm count, sperm concentration, motility score and yield after preparation. In conclusion, once infertility is established the HRG C633T SNP seems to be important for male infertility and pregnancy rate following IVF.

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  • 6.
    Lindgren, Karin Elvine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Yaldir, Fatma Gulen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hreinsson, Julius
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Karolinska Univ Hosp, Karolinska Inst, Dept Clin Sci Intervent & Technol, SE-14186 Stockholm, Sweden;Karolinska Univ Hosp, Unit Reprod Med, SE-14186 Stockholm, Sweden.
    Holte, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology. Carl von Linne Clin, SE-75183 Uppsala, Sweden.
    Kårehed, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Kaihola, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Differences in secretome in culture media when comparing blastocysts and arrested embryos using multiplex proximity assay2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 3, p. 143-152Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this study was to assess different patterns of the human embryo secretome analysed as protein levels in culture media. Furthermore, analyses to correlate protein levels with quality and timing to development of human embryos were performed.

    Material and methods: Human day-2 cryopreserved embryos were cultured for four days in an EmbryoScope((R)) with a time-lapse camera, and embryo quality was evaluated retrospectively. After culture, the media were collected and relative levels of secreted proteins were analysed using Proseek Multiplex Assays. Protein levels were evaluated in relation to timing to development and the ability to form a blastocyst.

    Results: Specific patterns of timing of development of blastocysts were found, where a difference in time to start of cavitation was found between high- and low-quality blastocysts. There appeared to be a correlation between specific protein patterns and successful formation of morulae and blastocysts. Embryos developing into blastocysts had higher levels of EMMPRIN than arrested embryos, and levels of caspase-3 were lower in high- versus low-quality blastocysts. Also, higher levels of VEGF-A, IL-6, and EMMPRIN correlated with shorter times to morula formation.

    Conclusions: The secretome and timing to development differ in embryos forming blastocysts and those that become arrested, and in high- versus low-quality blastocysts. The levels of certain proteins also correlate to specific times to development.

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  • 7.
    Nordqvist, Sarah
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kårehed, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hambiliki, Fredwell
    Department of Clinical Science, Karolinska Institutet, Stockholm, Sweden.
    Wånggren, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    The Presence of Histidine-Rich Glycoprotein in the Female Reproductive Tract and in Embryos2010In: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 17, no 10, p. 941-947Article in journal (Refereed)
    Abstract [en]

    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.

  • 8.
    Nordqvist, Sarah
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kårehed, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skoog Svanberg, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Menezes, Judith
    Fertilitetscentrum Stockholm.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Ovarian Response is Affected by a Specific Histidine-Rich Glycoprotein Polymorphism: a preliminary study2015In: Reproductive BioMedicine Online, ISSN 1472-6483, E-ISSN 1472-6491, Vol. 30, no 1, p. 74-81Article in journal (Refereed)
    Abstract [en]

    Genetic polymorphisms involved in angiogenesis, apoptosis and chemokine signalling are associated with varying ovarian response and oocyte quality. The protein, histidine-rich glycoprotein (HRG), is involved in these processes, but its effect on ovarian response in IVF has not been previously studied. A single nucleotide polymorphism (SNP) in the HRG gene (C633T) seems to affect pregnancy results in IVF. Women with the C/C genotype had higher pregnancy rates, C/T had moderate rates and none of those in the T/T group conceived. The aim of this study was to investigate if the HRG C633T SNP affects ovarian response. The HRG C633T SNP genotype of 67 women with unexplained infertility undergoing IVF was analysed and related to medical data. The T/T genotype obtained fewer oocytes, including mature oocytes, despite higher dosages of FSH administered. Additionally, the highest proportion of women who had exclusively poor-quality embryos was in the T/T group. No differences in demographic factors known to affect these parameters were found. The results suggest that the HRG C633T SNP influences ovarian response. Further studies of this SNP may increase knowledge about the biological processes involved in oocyte development and, furthermore, improve predicted ovarian response and fertilization.

  • 9.
    Nordqvist, Sarah
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kårehed, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Stavreus-Evers, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Histidine-Rich Glycoprotein Polymorphism and Pregnancy Outcome: a pilot study2011In: Reproductive BioMedicine Online, ISSN 1472-6483, E-ISSN 1472-6491, Vol. 23, no 2, p. 213-219Article in journal (Refereed)
    Abstract [en]

    Histidine-rich glycoprotein (HRG) is involved in fibrinolysis and coagulation, the immune system and angiogenesis. These processes are all crucial in establishing and maintaining pregnancy. The primary aim of this pilot study was to determine if HRG affects pregnancy outcome. The secondary aim was to investigate if a specific genetic polymorphism (rs9898 C/T) in the HRG gene is associated with pregnancy results. The polymorphism leads to expression of either a serine or proline residue at position 186 in the protein sequence. In this study, women undergoing IVF were included. The genetic polymorphism in the HRG gene was analysed by Western blot and single nucleotide polymorphism analysis. None of the women homozygous for the serine at residue 186 became pregnant whereas the women homozygous for proline at residue 186 had higher than expected pregnancy rates. As far as is known,this is the first study to show that a specific genetic polymorphism in the HRG gene of a woman affects her chances of becoming pregnant after IVF. The results may be essential in improving advice and IVF treatment for couples with unexplained infertility.

    We have found a new test which might potentially improve advice and treatment for infertile couples considering IVF treatment. Histidine-rich glycoprotein (HRG) is involved in the system preventing blood clots or excess bleeding, the immune system and the system regulating blood vessel formation. Tight regulation of these processes is necessary for a pregnancy to be successful. This study examines how a specific genetic variant of HRG can affect pregnancy rates after IVF. The genetic polymorphism leads to expression of two different protein variations. One variation has a serine amino acid attached at position 186 and the other variation has a proline amino acid attached at the same position. Which variation a women produces is inherited co-dominantly. In this study, women undergoing IVF were included. To determine which variation each woman had, two different methods were used: Western blot and single nucleotide polymorphism analysis. The experimental results were then related to the woman’s medical records. None of the women who only produced the variation of HRG with a serine attached became pregnant, whereas the women who produced only the proline variation had higher than expected pregnancy rates. We show for the first time that the genetic background of a woman may affect her chances of becoming pregnant after IVF. The results might be essential in improving advice and IVF treatment for infertile couples.

  • 10.
    Nordqvist, Sarah
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kårehed, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    IVF treatment is affected by Histidine-rich glycoprotein (HRG) polymorphism2013In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 28, no S1, p. 305-305Article in journal (Other academic)
  • 11.
    Nordqvist, Sarah
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kårehed, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    The Effect of SHB Gene Polymorphisms on Ovarian Response and Oocyte Maturation in IVF2014In: Reproduction, ISSN 1470-1626, E-ISSN 1476-3990Article in journal (Refereed)
  • 12.
    Thulin, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ringvall, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Dimberg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Kårehed, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Väisänen, Timo
    Biocenter Oulu, Department of Medical Biochemistry and Molecular Biology, University of Oulu, Finland.
    Väisänen, Marja-Riitta
    Biocenter Oulu, Department of Medical Biochemistry and Molecular Biology, University of Oulu, Finland.
    Hamad, Osama
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Wang, Jian
    Department of Biomedicine, University of Bergen, Norway.
    Bjerkvig, Rolf
    Department of Biomedicine, University of Bergen, Norway.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Pihlajaniemi, Taina
    Biocenter Oulu, Department of Medical Biochemistry and Molecular Biology, University of Oulu, Finland.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Pietras, Kristian
    Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm.
    Jahnen-Dechent, Wilhelm
    Department of Biomedical Engineering, RWTH, Aachen University, Biointerface Laboratory, Germany.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Olsson, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Activated platelets provide a functional microenvironment for the antiangiogenic fragment of histidine-rich glycoprotein2009In: Molecular Cancer Research, ISSN 1541-7786, E-ISSN 1557-3125, Vol. 7, no 11, p. 1792-1802Article in journal (Refereed)
    Abstract [en]

    The angiogenesis inhibitor histidine-rich glycoprotein (HRG) constitutes one of several examples of molecules regulating both angiogenesis and hemostasis. The antiangiogenic properties of HRG are mediated via its proteolytically released histidine- and proline-rich (His/Pro-rich) domain.Using a combination of immunohistochemistry and massspectrometry, we here provide biochemical evidence for thepresence of a proteolytic peptide, corresponding to the antiangiogenic domain of HRG, in vivo in human tissue. This finding supports a role for HRG as an endogenous regulator of angiogenesis. Interestingly, the His/Pro-rich peptide bound to the vessel wall in tissue from cancer patients but not to the vasculature in tissue from healthy persons.Moreover, the His/Pro-rich peptide was found in close association with platelets. Relesate from in vitro–activated platelets promoted binding of the His/Pro-rich domain of HRG to endothelial cells, an effect mediated by Zn2+.Previous studies have shown that zinc-dependent bindingof the His/Pro-rich domain of HRG to heparan sulfate on endothelial cells is required for inhibition of angiogenesis.We describe a novel mechanism to increase the local concentration and activity of an angiogenesis inhibitor,which may reflect a host response to counteract angiogenesis during pathologic conditions. Our finding that tumor angiogenesis is elevated in HRG-deficient mice supports this conclusion.

  • 13.
    Åkerud, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kårehed, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Histidine-rich glycoprotein and infertilityPatent (Other (popular science, discussion, etc.))
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