Research question

Proinflammatory advanced glycation end products (AGE), highly elevated within the uterine cavity of obese women, compromise endometrial function. Do AGE also impact preimplantation embryo development and function?

Design

Mouse embryos were cultured in AGE equimolar to uterine fluid concentrations in lean (1–2 µmol/l) or obese (4–8 µmol/l) women. Differential nuclear staining identified cell allocation to inner cell mass (ICM) and trophectoderm (TE) (day 4 and 5 of culture). Cell apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling assay (day 5). Day 4 embryos were placed on bovine serum albumin/fibronectin-coated plates and embryo outgrowth assessed 93 h later as a marker of implantation potential. AGE effects on cell lineage allocation were reassessed following pharmacological interventions: either 12.5 nmol/l AGE receptor (RAGE) antagonist; 0.1 nmol/l metformin; or combination of 10 µmol/l acetyl-l-carnitine, 10 µmol/l N-acetyl-l-cysteine, and 5 µmol/l alpha-lipoic acid.

Results

8 µmol/l AGE reduced: hatching rates (day 5, P < 0.01); total cell number (days 4, 5, P < 0.01); TE cell number (day 5, P < 0.01), and embryo outgrowth (P < 0.01). RAGE antagonism improved day 5 TE cell number.

Conclusions

AGE equimolar with the obese uterine environment detrimentally impact preimplantation embryo development. In natural cycles, prolonged exposure to AGE may developmentally compromise embryos, whereas following assisted reproductive technology cycles, placement of a high-quality embryo into an adverse ‘high AGE’ environment may impede implantation success. The modest impact of short-term RAGE antagonism on improving embryo outcomes indicates preconception AGE reduction via pharmacological or dietary intervention may improve reproductive outcomes for overweight/obese women.

中文翻译：

---

肥胖子宫环境中存在的晚期糖基化终产物会影响植入前胚胎发育

研究问题

促炎晚期糖基化终产物 (AGE) 在肥胖女性的子宫腔内高度升高，会损害子宫内膜功能。AGE 是否也会影响植入前胚胎的发育和功能？

设计

小鼠胚胎在与瘦 (1–2 µmol/l) 或肥胖 (4–8 µmol/l) 妇女的子宫液浓度等摩尔的 AGE 中培养。差异核染色确定细胞分配到内细胞团 (ICM) 和滋养外胚层 (TE)（培养的第 4 天和第 5 天）。通过末端脱氧核苷酸转移酶介导的 dUDP 缺口末端标记测定（第 5 天）检查细胞凋亡。第 4 天胚胎被放置在牛血清白蛋白/纤连蛋白包被的平板上，93 小时后评估胚胎生长作为植入潜力的标志。在药物干预后重新评估 AGE 对细胞谱系分配的影响：12.5 nmol/l AGE 受体 (RAGE) 拮抗剂；0.1 nmol/l 二甲双胍；或 10 µmol/l 乙酰-l-肉碱、10 µmol/l N-乙酰-l 的组合-半胱氨酸和 5 µmol/l α-硫辛酸。

结果

8 µmol/l AGE 降低：孵化率（第 5 天，P  < 0.01）；总细胞数（第 4、5 天，P  < 0.01）；TE 细胞数（第 5 天，P  < 0.01）和胚胎生长（P  < 0.01）。RAGE 拮抗作用改善了第 5 天的 TE 细胞数。

结论

与肥胖子宫环境等摩尔的 AGE 会对植入前胚胎发育产生不利影响。在自然周期中，长期暴露于 AGE 可能会损害胚胎的发育，而在辅助生殖技术周期之后，将高质量胚胎置于不利的“高 AGE”环境中可能会阻碍植入成功。短期 RAGE 拮抗剂对改善胚胎结局的适度影响表明，通过药物或饮食干预减少孕前 AGE 可能会改善超重/肥胖女性的生殖结局。