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The effect of a specific histidine-rich glycoprotein polymorphism on male infertility and semen parameters.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. (Reproduktiv hälsa/Sundström-Poromaa)
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.
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 Women's and Children's Health, Obstetrics and Gynaecology. (Reproduktiv hälsa/Sundström-Poromaa)
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2016 (English)In: Reproductive Biomedicine Online, ISSN 1472-6483, E-ISSN 1472-6491, Vol. 33, no 2, 180-188 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
2016. Vol. 33, no 2, 180-188 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-296211DOI: 10.1016/j.rbmo.2016.05.004ISI: 000380751000009PubMedID: 27210772OAI: oai:DiVA.org:uu-296211DiVA: diva2:936714
Funder
Swedish Research Council, D0277902, D0277901Swedish Society of MedicineStiftelsen Olle Engkvist Byggmästare
Available from: 2016-06-14 Created: 2016-06-14 Last updated: 2017-11-28Bibliographically approved
In thesis
1. The Histidine-rich Glycoprotein in Reproduction
Open this publication in new window or tab >>The Histidine-rich Glycoprotein in Reproduction
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Infertility affects 15% of reproductive-aged couples. The milieu surrounding the growing embryo is of outmost importance, and should be optimised during in vitro fertilisation (IVF). Many biological processes, such as angiogenesis, coagulation, and immune processes need to be well regulated for a pregnancy to occur and progress normally. Histidine-rich glycoprotein (HRG) is a plasma protein that regulates components of these systems by building complexes with various ligands. A single nucleotide polymorphism (SNP) in HRG, denoted HRG C633T, seem to be of importance for IVF treatment outcomes. The aim of this thesis was to further investigate the proposed human fertility effects of the HRG C633T SNP.

According to the findings of this thesis, the HRG C633T genotype is associated with primary recurrent miscarriage. Male HRG C633T genotype is associated with semen characteristics in infertile men, and pregnancy rates following IVF. However, the distribution of the HRG C633T SNP does not differ between infertile and fertile couples.

We further examined the role of the region surrounding the HRG C633T SNP for regulation of endometrial angiogenesis and human embryo development. The region affects primary endometrial endothelial cell migration, proliferation and tube-formation in vitro but does not appear to affect human embryo development. No effect of the HRG peptide was noted on the secretome of human embryos. However, early embryos secrete proteins into the surrounding culture media and the level of secretion of VEGF-A, IL-6, EMMPRIN and PlGF is greater in embryos of higher developmental stages.

In conclusion, the HRG C633T genotype appears to play a role only if infertility is established. The region surrounding HRG C633T SNP is of relevance in vitro for regulation of human endometrial endothelial cell angiogenesis. To predict which embryos to transfer in IVF, we have highlighted a number of proteins of interest for further investigation.     

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 76 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1244
Keyword
Angiogenesis, embryo culture medium, embryogenesis, embryonic secretome, endometrium, histidine-rich glycoprotein, human embryo development, human embryo implantation, human endometrial endothelial cells, in vitro fertilisation, infertility, male infertility, proximity extension assay, recurrent miscarriage, single nucleotide polymorphism, sperm quality, time-lapse technique, vascular endothelial growth factor
National Category
Medical and Health Sciences Obstetrics, Gynecology and Reproductive Medicine Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-300769 (URN)978-91-554-9648-7 (ISBN)
External cooperation:
Public defence
2016-09-30, Auditorium minus, Museum Gustavianum, Akademigatan 3, Uppsala, 09:15 (English)
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Supervisors
Available from: 2016-09-09 Created: 2016-08-12 Last updated: 2016-09-13

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Lindgren, Karin E

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