Reproduction Abstracts

Introduction: Uterine natural killer (uNK) cells have a largely recognised role in normal uterine function, particular successful pregnancy. We have previously found that infertile women have more uNK progenitor cells than fertile women. We aim to study the differentiation of uNK cells in women with endometriosis.

Material and methods: Numbers and phenotype of uNKs (CD45+, CD56+, CD3+, and CD16−) were defined using flow cytometry: CD10, CD34, CD94, CD117, CD161, integrinβ7, and NKp46. Levels of interleukin 15 (IL15), stem cell factor (SCF), and IGF1 were analysed using qRT-PCR and western blot. CD56+CD34+ cells were detected using double immunohistochemistry. CD34+ (progenitor marker) cells were isolated from endometrial biopsies and cultured with IL15, SCF, and IGF1.

Results and discussion: CD56+ cell numbers were higher in women with endometriosis when compared with unaffected women. This appears to be because UNK progenitors (CD56+CD34+) at all phases of development were also higher in women with endometriosis. Additionally, NK growth factors (GFs) IL15, SCF, and IGF1 are reduced in women with endometriosis. Culturing CD34+ endometrial cells from women with and without endometriosis with these GFs resulted in higher numbers of mature NK cells from women with endometriosis.

This study shows for the first time that altered uNK maturation, as evidenced by accumulated progenitor cells and abnormal levels of significant GFs, occurs in endometriosis. Replacement of these GFs in cell culture restores NK maturation. Stunted development of a cell vital for fertility, uNK cells, provides an explanation for endometriosis-related infertility.