title: Histidine-rich glycoprotein derived peptides affect endometrial angiogenesis in vitro but has no effect on embryo development.
abstract: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: a Department of Women's and Children's Health , Uppsala University , Uppsala , Sweden.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Lindgren
authors.affiliation: a Department of Women's and Children's Health , Uppsala University , Uppsala , Sweden.|b IVF Sweden, IVF-Clinic Falun , Falun , Sweden.
authors.forename: Julius
authors.initials: J
authors.lastname: Hreinsson
authors.affiliation: a Department of Women's and Children's Health , Uppsala University , Uppsala , Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Helmestam
authors.affiliation: a Department of Women's and Children's Health , Uppsala University , Uppsala , Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Wånggren
authors.affiliation: a Department of Women's and Children's Health , Uppsala University , Uppsala , Sweden.
authors.forename: Inger Sundström
authors.initials: IS
authors.lastname: Poromaa
authors.affiliation: a Department of Women's and Children's Health , Uppsala University , Uppsala , Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Kårehed
authors.affiliation: a Department of Women's and Children's Health , Uppsala University , Uppsala , Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Åkerud
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D015925:Cryopreservation; D047108:Embryonic Development; D004717:Endometrium / Q000098:blood supply*; D005260:Female; D006801:Humans; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000378:metabolism; D011506:Proteins / Q000502:physiology*; D019699:Thrombospondins / Q000096:biosynthesis; D000099053:Histidine-Rich Glycoprotein
chemical_list: D010455:Peptides; D011506:Proteins; D019699:Thrombospondins; D000099053:Histidine-Rich Glycoprotein
keywords: Angiogenesis; HRG; endothelial cells; human embryo culture; single nucleotide polymorphism