Immunoexpression of DNA fragmentation factor 40, DNA fragmentation factor 45, and B-cell lymphoma 2 protein in normal human endometrium and uterine myometrium depends on menstrual cycle phase and menopausal status

Arch Med Sci. 2018 Oct;14(6):1254-1262. doi: 10.5114/aoms.2017.69383. Epub 2017 Jul 31.

Abstract

Introduction: DNA fragmentation factors 40 and 45 (DFF40 and DFF45) are final executors of apoptosis, and B-cell lymphoma 2 (Bcl-2) is a well-recognized apoptosis inhibitor. We aimed to evaluate DFF40, DFF45 and Bcl-2 immunoexpression in the normal human endometrium with respect to the glandular and stromal layer and in uterine myometrium.

Material and methods: DFF40, DFF45, and Bcl-2 expression was assessed via immunohistochemistry in the endometrium and myometrium collected postmenopausally and premenopausally during the proliferative and secretory phases of the menstrual cycle.

Results: Compared to the myometrium and stroma, endometrial glands showed the highest DFF40 and DFF45 expression in pre- and postmenopausal specimens. DFF45, but not DFF40, glandular expression dependent on menstrual cycle phase and DFF40 and DFF45 scoring was significantly lower in postmenopausal specimens. Significantly higher Bcl-2 expression was observed in proliferative glandular endometrium compared to secretory and postmenopausal specimens. No cycle- or menopause-dependent changes were reported for stromal or myometrial DFF40, DFF45 or Bcl-2 expression. DFF40, DFF45 and Bcl-2 expression was independent of age, age at menarche and menopause, BMI, menstrual cycle and menses lengths, parity and gravidity.

Conclusions: The study provides important evidence regarding menstrual cycle-dependent changes in the expression of DFF40, DFF45 and Bcl-2 in the normal human endometrium, especially in the glandular layer, and shows that their levels are stable in the normal uterine myometrium.

Keywords: B-cell lymphoma 2; Bcl-2; DFF40; DFF45; DNA fragmentation factor 45; DNA fragmentation factors 40; endometrium; menstrual cycle; uterine myometrium.