Assisted Reproduction Unit, Jesús Usón Minimally Invasive Surgery Centre, Cáceres, Spain.
Department of Cell Biology, University of Extremadura, Badajoz, Spain.
Mol Hum Reprod. 2021 Feb 5;27(2). doi: 10.1093/molehr/gaaa075.
Embryo implantation in the uterus is a critical step to achieve success following ART. Despite favorable uterine conditions, a great number of good quality embryos fail to implant, often for reasons that are unknown. Hence, improving the implantation potential of embryos is a subject of great interest. 4-Hydroxyestradiol (4-OH-E2), a metabolic product of estradiol produced by endometrial cells, plays a key role in endometrial-embryonic interactions that are necessary for implantation. Nonetheless, the effects of 4-OH-E2 on embryos obtained in vitro have not been yet described. This study was designed to determine whether culture media enriched in 4-OH-E2 could improve the quality and implantation rate of embryos obtained in vitro, using both in vitro and in vivo models. We also analyzed its effects on the epidermal growth factor (EGF)-binding capability of the embryos. Our results showed that the presence of 4-OH-E2 in the culture media of embryos during the morula to blastocyst transition increases embryo quality and attachment to endometrial cells in vitro. 4-OH-E2 can also improve viable pregnancy rates of mouse embryos produced in vitro, reaching success rates that are similar to those from embryos obtained directly from the uterus. 4-OH-E2 improved the embryos' ability to bind EGF, which could be responsible for the increased embryo implantation potential observed. Therefore, our results strongly suggest that 4-OH-E2 is a strong candidate molecule to supplement human IVF culture media in order to improve embryo implantation. However, further research is required before these findings can be translated with efficacy and safety to fertility clinics.
胚胎在子宫内着床是辅助生殖技术（ART）成功的关键步骤。尽管子宫条件良好，但仍有大量优质胚胎无法着床，其原因通常未知。因此，提高胚胎着床能力是一个非常有吸引力的研究课题。4-羟基雌二醇（4-OH-E2）是子宫内膜细胞产生的雌二醇的代谢产物，在胚胎与子宫内膜相互作用中发挥关键作用，而胚胎着床则依赖于这种相互作用。然而，4-OH-E2 对体外获得的胚胎的影响尚未得到描述。本研究旨在使用体外和体内模型，确定富含 4-OH-E2 的培养基是否可以改善体外获得的胚胎的质量和着床率，并分析其对胚胎表皮生长因子（EGF）结合能力的影响。我们的研究结果表明，在胚胎从桑葚胚到囊胚过渡期间的培养基中添加 4-OH-E2 可以提高胚胎质量并增加胚胎在体外与子宫内膜细胞的黏附。4-OH-E2 还可以提高体外培养的小鼠胚胎的活产妊娠率，使其达到与直接从子宫中获得的胚胎相似的成功率。4-OH-E2 提高了胚胎结合 EGF 的能力，这可能是观察到的胚胎着床潜力增加的原因。因此，我们的研究结果强烈表明，4-OH-E2 是一种很有前途的候选分子，可以用于补充人类体外受精培养基，以提高胚胎着床。然而，在这些发现能够有效地、安全地应用于生育诊所之前，还需要进一步的研究。
