Chambliss Christopher, Manci Elizabeth, Fields Earl, Bueno Jesse, Michael Adeola, Eldeiry Elizabeth, Hall Cameron, Gee Beatrice, Chonat Satheesh, Archer David R
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
Children's Healthcare of Atlanta, Aflac Cancer and Blood Disorders Center, Atlanta, Georgia, USA.
Br J Haematol. 2025 Sep;207(3):813-823. doi: 10.1111/bjh.70024. Epub 2025 Jul 20.
Although increased risk for adverse pregnancy outcomes has been well characterized in women with sickle cell disease (SCD), there remains unexplored value in the characterization of a preclinical model which could minimize human risk. This study aimed to characterize pregnancy outcomes in the SCD mouse model with emphasis on analogous clinical correlates and biological contributors. As such, we identified worsened outcomes including reduced litter sizes (haemoglobin HbSS (SS) 5.18 ± 1.25 embryos vs. haemoglobin HbAA (AA) 6.86 ± 1.51**), fetal weight (SS 0.38 ± 0.16 g vs. AA 0.49 ± 0.14 g**), viability of embryos (SS 20.00% interquartile range (IQR) 33.33 vs. AA 100.00% IQR 0.0***) and maternal mortality (SS 7.14% (2/28) vs. AA 0.00% (0/27) odds ratio (OR) = 4.82 ns). We further noted a significant reduction in vascular density and impaired uterine and umbilical artery blood flow within SCD placentae. Assessments of soluble growth factors revealed evidence of angiogenic dysregulation but maintained limited translational utility due to the multiparous nature of mouse pregnancy. These results serve as a cornerstone characterization of pregnancy outcomes in the SCD mouse model while highlighting the implications of placental vascular insufficiency. They further demonstrate both the utility and limitations of the model, emphasizing the need for continued clinical assessment.
尽管镰状细胞病（SCD）女性不良妊娠结局的风险增加已得到充分描述，但在一个可将人类风险降至最低的临床前模型的特征描述方面，仍有未被探索的价值。本研究旨在描述SCD小鼠模型中的妊娠结局，重点关注类似的临床相关性和生物学因素。因此，我们确定了不良结局，包括窝仔数减少（血红蛋白HbSS（SS）组为5.18±1.25只胚胎，而血红蛋白HbAA（AA）组为6.86±1.51只**）、胎儿体重（SS组为0.38±0.16克，AA组为0.49±0.14克**）、胚胎存活率（SS组四分位数间距（IQR）为20.00%，范围为33.33，而AA组为100.00%，IQR为0.0***）和孕产妇死亡率（SS组为7.14%（2/28），AA组为0.00%（0/27），优势比（OR）=4.82，无显著性差异）。我们还进一步注意到SCD胎盘内血管密度显著降低，子宫和脐动脉血流受损。对可溶性生长因子的评估显示存在血管生成失调的证据，但由于小鼠妊娠的多胎性质，其转化应用价值有限。这些结果是SCD小鼠模型妊娠结局的基础特征描述，同时突出了胎盘血管功能不全的影响。它们进一步证明了该模型的实用性和局限性，强调了持续进行临床评估的必要性。
