Research question

Is the blastocyst's idiosyncratic metabolic production of lactate, and creation of a specialized microenvironment at the implatation site, an important mediator of maternal–fetal signalling to promote endometrial receptivity and implantation?

Design

Hormonally primed ECC-1 and Ishikawa cells were used to assess functional changes to the endometrial epithelium after exposure to lactic acid (LA), LA with neutralized pH (nLA) or acidic pH (pH_L). Tight junction integrity (transepithelial resistance [TER]), cellular proliferation or changes to gene expression by RT-PCR were analysed. The effect of LA on Endometrial stromal cells decidualization and migratory capacity, and HUVEC endothelial tube formation and angiogenesis, were also assessed.

Results

Treatment of ECC-1 cells with 2.5 mM (P = 0.0037), 5 mM (P = 0.0044), 7.5 mM and 10 mM (P = 0.003) (P = 0.0021) LA significantly decreased the rate of cellular proliferation while TER was decreased with exposure to 2.5 mM LA (P = 0.024), 5 mM LA (P = 0.021) and 7.5 mM LA (P = 0.033). Exposure to nLA or pH_L had no effect on proliferation or TER. Upregulation of GLUT4 (P = 0.002), GPR81 (P = 0.048), VEGF, SNAI1 (both P < 0.001) and RELA (P = 0.023) mRNA expression was observed after exposure of Ishikawa cells to combined LA plus pH_L. Lactic acid increased the migratory capacity of decidualized stromal cells (P = 0.047) without changing the extent of decidualization. HUVEC tube formation was significantly increased by 5 mM LA exposure (P = 0.009).

Conclusions

The identification of LA as an important mediator in the maternal–fetal dialogue underpinning implantation is supported. Further examination of the role of LA within the infertile or compromised endometrium could improve natural and assisted pregnancy success and needs further investigation.

中文翻译：

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由胚泡创造的高乳酸和低 pH 微环境促进子宫内膜容受性和着床

研究问题

胚泡特殊的乳酸代谢产生，以及在着床部位形成的特殊微环境，是否是促进子宫内膜容受性和着床的母胎信号传导的重要介质？

设计

激素引发的 ECC-1 和 Ishikawa 细胞用于评估暴露于乳酸 (LA)、具有中和 pH 值 (nLA) 或酸性 pH 值 (pH _L ) 的 LA 后子宫内膜上皮的功能变化。通过 RT-PCR 分析了紧密连接完整性（跨上皮电阻 [TER]）、细胞增殖或基因表达的变化。还评估了 LA 对子宫内膜基质细胞蜕膜和迁移能力以及 HUVEC 内皮管形成和血管生成的影响。

结果

用 2.5 mM ( P  = 0.0037)、5 mM ( P  = 0.0044)、7.5 mM 和 10 mM ( P = 0.003) ( P = 0.0021) LA处理 ECC-1 细胞 显着降低细胞增殖率而 TER 降低暴露于 2.5 mM LA ( P = 0.024)、5 mM LA ( P = 0.021) 和 7.5 mM LA ( P = 0.033)。暴露于 nLA 或 pH _L对增殖或 TER 没有影响。GLUT4 ( P = 0.002)、GPR81 ( P = 0.048)、VEGF、SNAI1 (均P < 0.001) 和RELA ( P =0.023) 将 Ishikawa 细胞暴露于 LA 加 pH _L组合后观察到 mRNA 表达。乳酸增加了蜕膜基质细胞的迁移能力（P  = 0.047），而不改变蜕膜的程度。5 mM LA 暴露显着增加了 HUVEC 管的形成 ( P  = 0.009)。

结论

支持将 LA 确定为支持植入的母胎对话中的重要介质。进一步检查 LA 在不孕或受损子宫内膜中的作用可以提高自然妊娠和辅助妊娠的成功率，需要进一步研究。