Maternal and Fetal Health Centre and Division of Developmental Biology and Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences Centre, St Mary's Hospital, Manchester M13 9WL, UK.
Department of Reproductive Medicine, Old St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Oxford Road, Manchester M13 9WL, UK.
Mol Hum Reprod. 2019 May 1;25(5):265-273. doi: 10.1093/molehr/gaz011.
Implantation failure is an important impediment to increasing success rates in assisted reproductive technologies. Knowledge of the cascade of morphological and molecular events at implantation remains limited. Cell surface CD44 and hyaluronate (HA) have been reported in the uterus, but a role in intercellular interaction at implantation remains to be evaluated. Mouse embryos were co-cultured with human Ishikawa endometrial epithelial monolayers over 2 days. Attachment was tenuous during the first 24 h, after which it became stable, leading to breaching of the monolayer. The effects of enzymatically reducing the density of HA, or introducing a function-blocking antibody to CD44, were monitored during progression from weak to stable embryonic attachment. Hyaluronidase-mediated removal of surface HA from the epithelial cells enhanced the speed of attachment, while a similar treatment of embryos had no effect. The antibody to CD44 caused retardation of initial attachment. These results suggest that CD44-HA binding could be employed by embryos during initial docking, but the persistence of HA in epithelial cells might be detrimental to later stages of implantation by retarding attainment of stable attachment.
着床失败是辅助生殖技术提高成功率的一个重要障碍。对着床过程中形态和分子事件的级联反应的认识仍然有限。细胞表面 CD44 和透明质酸（HA）已在子宫中报道，但在着床过程中的细胞间相互作用中的作用仍有待评估。将小鼠胚胎与人类 Ishikawa 子宫内膜上皮单层共培养 2 天。在前 24 小时内，附着很脆弱，之后变得稳定，导致单层破裂。在从弱附着到稳定胚胎附着的过程中，监测了通过酶降低 HA 密度或引入针对 CD44 的功能阻断抗体的影响。透明质酸酶介导的去除上皮细胞表面的 HA 可加快附着速度，而对胚胎进行类似处理则没有影响。针对 CD44 的抗体导致初始附着延迟。这些结果表明，CD44-HA 结合可被胚胎用于初始对接，但上皮细胞中 HA 的持续存在可能通过延迟达到稳定附着而不利于着床的后期阶段。
