Histidine-rich glycoprotein derived peptides affect endometrial angiogenesisin vitrobut has no effect on embryo development

Abstract

(2016) Histidine-rich glycoprotein derived peptides affect endometrial angiogenesis invitro but has no effect on embryo development, Systems Biology in Reproductive Medicine, 62:3, 192-200, DOI: 10.3109/19396368.2016.1156785 To link to this article: https://doi.org/10. 3109/19396368.2016 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.

HRG C633T polymorphism and risk of gestational hypertensive disorders: a pilot study

“…heterozygous C/T and homozygous T/T carrier status) is associated with a risk of developing gestational hypertensive disorders. Our findings are in line with previous studies demonstrating the T-minor allele (homozygous T/T genotype) to be less favourable, both regarding fertility [ 9 , 16 , 17 ] and the occurrence of recurrent pregnancy loss [ 14 ].…”

“…Furthermore, specific HRG polymorphisms have been associated with recurrent miscarriage [ 13 , 14 ] and infertility [ 9 ] with the possible hypothesis that the amino acid substitution induces a conformational change on the HRG protein which affects its function [ 15 ]. It has thus been further hypothesized that HRG, by regulating angiogenesis, might be an important intermediary for adequate implantation and placentation [ 16 ] . Nonetheless, gene expression studies, validated by proteomics and metabolomics, are required in order to fully understand the underlying regulatory pathways involved in fertility and pregnancy related disorders.…”

Live births after embryo selection using morphokinetics versus conventional morphology: a retrospective analysis

“…Such technology has captured the imagination of practitioners as both a research tool (Costa-Borges et al, 2016;Hardarson et al, 2015;Mölder et al, 2015), comparing embryos resulting from various clinical conditions (Balakier et al, 2016;Gurbuz et al, 2016;Hashimoto et al, 2016;Kaihola et al, 2016;Lindgren et al, 2016), and as a potential prognosticator in clinical practice (Adamson et al, 2016;Chen et al, 2016;Kong et al, 2016;Liu et al, 2016;Milewski et al, 2015;Mizobe et al, 2016;Rubio et al, 2014;VerMilyea et al, 2014;Wu et al, 2016aWu et al, , 2016bYang et al, 2014), although some studies negate this (Freour et al, 2015;Wu et al, 2016aWu et al, , 2016b. Bronet et al (2015) even found distinctive morphokinetic differences between male and female embryos.…”

Genetic Causes of Recurrent Miscarriages

“…This protein is synthesized in liver [24]. Some studies showed that HGR acts in implantation process, embryo development and fertility [25,26]. In their study Lindgren et al were trying to find association between HRG C633T SNP and RSA [24].…”