Department of Obstetrics and Gynecology, School of Medicine, Balikesir University, Cagis Yerleskesi Bigadic yolu 17 km pc, 10145, Balikesir, Turkey.
Department of Pathology, School of Medicine, Balikesir University, Balikesir, Turkey.
Reprod Sci. 2021 May;28(5):1447-1456. doi: 10.1007/s43032-020-00423-z. Epub 2021 Jan 15.
The objective of this study was to investigate proliferation, apoptosis, and antiapoptotic molecule expression in endometrial cells of reproductive-aged women with and without type II diabetes mellitus (T2D). In this case-control study, a total of 80 endometrial tissue specimens from reproductive-aged women (35 in the proliferative phase and 45 in the secretory phase) were examined. The age and body mass index (BMI) were matched between the groups. Formalin-fixed and paraffin-embedded endometrial tissue samples were used for immunohistochemistry analysis. The presence of proliferation was evaluated with Ki-67 expression, antiapoptotic function of cells was evaluated with Bcl-2 expression, and apoptosis was evaluated with terminal deoxynucleotidyl transferase (TUNEL) immunoreactivity in both the glandular epithelium and stroma of endometrial tissue samples from women with and without T2D. Ki-67 expression in the glandular epithelium and Bcl-2 expression in both the glandular epithelium and stroma were significantly higher in endometrial tissue samples of women in the T2D group than the control group (p = 0.0008, p = 0.0022, and p = 0.0261, respectively). TUNEL immunoreactivity was significantly lower in the glandular epithelium of women in the T2D group than the control group (p = 0.0001). Glandular Ki-67 expression correlated positively with BMI, use of insulin, and hemoglobin A1c level (p = 0.0034, p = 0.0154, and p = 0.0011, respectively). Glandular Bcl-2 expression correlated positively with BMI and duration of T2D (p = 0.0090 and p = 0.0109, respectively). Stromal Bcl-2 expression correlated positively with duration of T2D (p = 0.0069). TUNEL immunoreactivity in the glandular epithelium correlated negatively with duration of T2D (p = 0.0340) and positively with the use of oral antidiabetic agents (p = 0.0226). Compared to age and BMI-matched controls, women with T2D experienced increased cell proliferation and decreased apoptosis in the glandular epithelium and increased antiapoptotic function in both the glandular epithelium and stromal cells. High BMI values in women with diabetes seemed to contribute to increased cell proliferation and increased antiapoptotic function in the glandular epithelium but not the stromal cells.
本研究旨在探讨生殖年龄段患有 2 型糖尿病（T2D）和不患有 2 型糖尿病的女性子宫内膜细胞的增殖、凋亡和抗凋亡分子表达情况。在这项病例对照研究中，共检查了 80 名生殖年龄段女性的子宫内膜组织标本（增殖期 35 例，分泌期 45 例）。两组的年龄和体重指数（BMI）相匹配。使用免疫组织化学分析固定在福尔马林和石蜡包埋的子宫内膜组织样本。Ki-67 表达评估细胞增殖，Bcl-2 表达评估细胞抗凋亡功能，TUNEL 免疫反应性评估子宫内膜组织样本中腺体上皮和基质中的细胞凋亡。T2D 组女性的腺体上皮中的 Ki-67 表达和腺体上皮和基质中的 Bcl-2 表达明显高于对照组（p=0.0008，p=0.0022 和 p=0.0261）。T2D 组女性的腺体上皮中的 TUNEL 免疫反应性明显低于对照组（p=0.0001）。腺体 Ki-67 表达与 BMI、胰岛素使用和糖化血红蛋白水平呈正相关（p=0.0034，p=0.0154 和 p=0.0011）。腺体 Bcl-2 表达与 BMI 和 T2D 持续时间呈正相关（p=0.0090 和 p=0.0109）。基质 Bcl-2 表达与 T2D 持续时间呈正相关（p=0.0069）。腺体上皮中的 TUNEL 免疫反应性与 T2D 持续时间呈负相关（p=0.0340），与口服抗糖尿病药物的使用呈正相关（p=0.0226）。与年龄和 BMI 匹配的对照组相比，患有 T2D 的女性的腺体上皮中细胞增殖增加，凋亡减少，腺体上皮和基质细胞中的抗凋亡功能增加。患有糖尿病的女性的高 BMI 值似乎导致腺体上皮中细胞增殖和抗凋亡功能增加，但对基质细胞没有影响。
