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Tissue Factor and Tissue Factor Pathway Inhibitors TFPI and TFPI2 in Human Secretory Endometrium—Possible Link to Female Infertility

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Abstract

The aim of this study was to investigate tissue factor (TF) and its inhibitors TFPI and TFPI2 in secretory endometrium of fertile women and in women with unexplained infertility in relation to endometrial receptivity. In addition, common variation in the regulatory area of TF and TFPI genes was studied. Immunostaining of TF and TFPI, together with the appearance of pinopodes, revealed similar expression pattern in fertile endometrium throughout the secretory phase, being highest at the time of implantation. When compared protein expression levels at the time of implantation, infertile women demonstrated significantly higher TFPI expression in luminal epithelium. Furthermore, polymorphism TF-603 A/G was associated with the endometrial protein level in infertile women, being highest in women with GG genotype, and variation TFPI-287 T/C was associated with unexplained infertility, where infertile women presented more frequently T allele than fertile women. Contrary to TF and TFPI, TFPI2 showed different mRNA and protein expression patterns in fertile endometrium, and no differences between fertile and infertile women were detected. We conclude that the TF pathway is involved in normal endometrial maturation, where TF and TFPI seem to have important roles at the time of embryo implantation. Higher TFPI expression level during the time of embryo implantation and TFPI-287 T allele could be risk factors for unexplained infertility. No distinct involvement of TFPI2 in the regulation of endometrial receptivity and unexplained infertility was found.

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Authors and Affiliations

  1. Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynaecology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

    Signe Altmäe PhD, Kerstin Bjuresten MSc, Britt-Marie Landgren MD, PhD & Outi Hovatta MD, PhD

  2. Competence Centre on Reproductive Medicine and Biology, Tartu, Estonia

    Signe Altmäe PhD & Andres Salumets PhD

  3. Department of Obstetrics and Gynaecology, University of Tartu, Tartu, Estonia

    Andres Salumets PhD

  4. Department of Women’s and Children’s Health, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden

    Theodora Kunovac Kallak MSc, Kjell Wånggren MD, PhD & Anneli Stavreus-Evers PhD

  5. Department of Obstetrics and Gynaecology K57, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186, Stockholm, Sweden

    Signe Altmäe PhD

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  1. Signe Altmäe PhD
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  2. Andres Salumets PhD
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Correspondence to Signe Altmäe PhD.

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Altmäe, S., Salumets, A., Bjuresten, K. et al. Tissue Factor and Tissue Factor Pathway Inhibitors TFPI and TFPI2 in Human Secretory Endometrium—Possible Link to Female Infertility. Reprod. Sci. 18, 666–678 (2011). https://doi.org/10.1177/1933719111400633

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