Seneszenz im Endometrium
Investigation of uterine NK-cells and age in the infertile endometrium
cand. Dr. med. Anne-Christin Wrzal
supervisor Dr. rer. nat. Astrid Schmidt
gefördert im Rahmen des JSAM 2021/ 2022
associated students: cand. Dr. med. Lingyu Wei, Yaroslava Anoshko
Uterine Natural Killer (uNK) cells in the endometrium are required for successful implantation and placentation. In contrast to cytotoxic peripheral blood NK cells endometrial uNKs are immunoregulatory [1]. Nevertheless, patients with fertility problems show lower or higher uNK cell concentration compared to a mid range in fertile women [2]. The aim of this study is to determine, whether indications of senescence can be found in the endometrium of patients with Recurrent Implantation Failure (RIF) and if so whether the expression of this senescence markers is associated with the age of the patient and/or the uNK cell concentration. The number of CD56+ uNK cells, CD138+ plasma cells and CD16+ cells as well as the expression of the senescence markers p16 and DIO2 were assessed by immunohistochemistry in endometrial biopsies from 63 RIF patients and 10 healthy controls (day 19-22). Pathologic and CD138 positive patients were excluded. An exemplary proteome analysis was performed using mass spectroscopy by using the eFASP method. Multiplex staining was performed to visualise the spacial relationships between the markers p16, DIO2, CD56, CK AE1/AE3 and CD31. Initial analyses show increased expression of senescence markers in RIF patients compared to healthy controls. In the groups with high uNK cell counts (>300 cells/mm2 ), a higher senescence marker expression was found than in the group with low concentrations (<100 cells/mm2). This findings will be validated by further data analysis of this study.
[1] S. Farag, M.A. Caligiuri, Human natural killer cell development and biology, Blood Rev 20(3) (2006) 123-37.
[2] Chiokadze, C. Bär, J. Pastuschek, B.V. Dons'koi, K.G. Khazhylenko, E. Schleussner, U.R. Markert, R.R. Favaro, Beyond Uterine Natural Killer Cell Numbers in Unexplained Recurrent Pregnancy Loss: Combined Analysis of CD45, CD56, CD16, CD57, and CD138, Diagnostics (Basel) 10(9) (2020).