Abstract：
OBJECTIVE: Does type 1 diabetes mellitus (T1DM) affect reproductive health of female patients? What is the potential mechanism of reproductive dysfunction in female patients caused by T1DM?
METHODS: Preliminary assessment of serum levels of female hormones in women with or without T1DM. Then histological and immunological examinations were carried out on the pancreas, ovaries and uteri at different stages in non-obese diabetic (NOD) and Institute of Cancer Research (ICR) mice, as well as assessment of their fertility. A protein array was carried out to detect the changes in serum inflammatory cytokines. Furthermore, RNA-sequencing was used to identify the key abnormal genes/pathways in ovarian and uterine tissues of female NOD mice, which were further verified at the protein level.
RESULTS: Testosterone levels were significantly increased (P = 0.0036) in female mice with T1DM. Increasing age in female NOD mice was accompanied by obvious lymphocyte infiltration in the pancreatic islets. Moreover, the levels of serum inflammatory factors in NOD mice were sharply increased with increasing age. The fertility of female NOD mice declined markedly, and most were capable of conceiving only once. Furthermore, ovarian and uterine morphology and function were severely impaired in NOD female mice. Additionally, ovarian and uterine tissues revealed that the differentially expressed genes were primarily enriched in metabolism, cytokine-receptor interactions and chemokine signalling pathways.
CONCLUSIONS: T1DM exerts a substantial impairment on female reproductive health, leading to diminished fertility, potentially associated with immune disorders and alterations in energy metabolism.
METHODS: Preliminary assessment of serum levels of female hormones in women with or without T1DM. Then histological and immunological examinations were carried out on the pancreas, ovaries and uteri at different stages in non-obese diabetic (NOD) and Institute of Cancer Research (ICR) mice, as well as assessment of their fertility. A protein array was carried out to detect the changes in serum inflammatory cytokines. Furthermore, RNA-sequencing was used to identify the key abnormal genes/pathways in ovarian and uterine tissues of female NOD mice, which were further verified at the protein level.
RESULTS: Testosterone levels were significantly increased (P = 0.0036) in female mice with T1DM. Increasing age in female NOD mice was accompanied by obvious lymphocyte infiltration in the pancreatic islets. Moreover, the levels of serum inflammatory factors in NOD mice were sharply increased with increasing age. The fertility of female NOD mice declined markedly, and most were capable of conceiving only once. Furthermore, ovarian and uterine morphology and function were severely impaired in NOD female mice. Additionally, ovarian and uterine tissues revealed that the differentially expressed genes were primarily enriched in metabolism, cytokine-receptor interactions and chemokine signalling pathways.
CONCLUSIONS: T1DM exerts a substantial impairment on female reproductive health, leading to diminished fertility, potentially associated with immune disorders and alterations in energy metabolism.
摘要：
目的：1型糖尿病（T1DM）是否影响女性患者的生殖健康？T1DM导致女性患者生殖功能障碍的潜在机制是什么？
方法：初步评估有或没有T1DM的女性血清雌性激素水平。然后对胰腺进行组织学和免疫学检查，非肥胖糖尿病（NOD）和癌症研究所（ICR）小鼠的卵巢和子宫处于不同阶段，以及对其生育能力的评估。进行蛋白质阵列以检测血清炎性细胞因子的变化。此外，RNA测序用于鉴定雌性NOD小鼠卵巢和子宫组织中的关键异常基因/途径。这在蛋白质水平上得到了进一步验证。
结果：在患有T1DM的雌性小鼠中睾酮水平显著升高(P=0.0036)。雌性NOD小鼠的年龄增加伴随着胰岛中明显的淋巴细胞浸润。此外，NOD小鼠血清炎症因子水平随日龄增加而急剧升高。雌性NOD小鼠的生育力明显下降，大多数人只能怀孕一次。此外，NOD雌性小鼠的卵巢和子宫形态和功能严重受损。此外,卵巢和子宫组织显示，差异表达的基因主要富集在代谢中，细胞因子-受体相互作用和趋化因子信号通路。
结论：T1DM对女性生殖健康有实质性损害，导致生育率下降，可能与免疫紊乱和能量代谢改变有关。
方法：初步评估有或没有T1DM的女性血清雌性激素水平。然后对胰腺进行组织学和免疫学检查，非肥胖糖尿病（NOD）和癌症研究所（ICR）小鼠的卵巢和子宫处于不同阶段，以及对其生育能力的评估。进行蛋白质阵列以检测血清炎性细胞因子的变化。此外，RNA测序用于鉴定雌性NOD小鼠卵巢和子宫组织中的关键异常基因/途径。这在蛋白质水平上得到了进一步验证。
结果：在患有T1DM的雌性小鼠中睾酮水平显著升高(P=0.0036)。雌性NOD小鼠的年龄增加伴随着胰岛中明显的淋巴细胞浸润。此外，NOD小鼠血清炎症因子水平随日龄增加而急剧升高。雌性NOD小鼠的生育力明显下降，大多数人只能怀孕一次。此外，NOD雌性小鼠的卵巢和子宫形态和功能严重受损。此外,卵巢和子宫组织显示，差异表达的基因主要富集在代谢中，细胞因子-受体相互作用和趋化因子信号通路。
结论：T1DM对女性生殖健康有实质性损害，导致生育率下降，可能与免疫紊乱和能量代谢改变有关。
