Toma Chihiro, Kuramoto Goro, Homma Jun, Sakaguchi Katsuhisa, Shimizu Tatsuya
Department of Obstetrics and Gynecology, Tokyo Women's Medical University, Tokyo, JPN.
Department of Clinical Regenerative Medicine, The Center for Advanced Reproductive Medicine, Fujita Medical Innovation Center Tokyo, Tokyo, JPN.
Cureus. 2023 Nov 28;15(11):e49613. doi: 10.7759/cureus.49613. eCollection 2023 Nov.
Infertility in women is associated with various uterine and ovarian disorders. Treatment strategies for infertility can range from medications to embryo implantation through assisted reproductive technology (ART). ART has enabled considerable progress; however, there is currently no treatment to replace the endometrium itself. Decidualization requires a complex interaction between endometrial tissue and estrogen and progesterone. We aimed to create a three-dimensional endometrial-like tissue model using in-vitro cell sheet engineering with rat endometrium, and culture cells at different progesterone concentrations to mimic local concentrations. Histological and morphological changes revealed that development of the endometrial-like tissue was not proportional to progesterone concentrations in terms of thickness, number of endometrial glands, or area fraction of intimal glands. These results suggest that decidualization may not be commensurate with the local endometrial progesterone concentration. Notably, the number of endometrial glands increased in the high concentration group and compaction occurred, indicating that the endometrial conditions in the high concentration group may be most conducive to increase pregnancy rates. These findings suggest that there may be an "optimal progesterone concentration" for decidualization, application of which may lead to new strategies for improving pregnancy rates in women with infertility.
女性不孕症与多种子宫和卵巢疾病相关。不孕症的治疗策略涵盖从药物治疗到通过辅助生殖技术(ART)进行胚胎植入。ART已取得了显著进展;然而,目前尚无能够替代子宫内膜本身的治疗方法。蜕膜化需要子宫内膜组织与雌激素和孕激素之间进行复杂的相互作用。我们旨在利用大鼠子宫内膜的体外细胞片工程技术创建一种三维子宫内膜样组织模型,并在不同孕激素浓度下培养细胞以模拟局部浓度。组织学和形态学变化显示,就厚度、子宫内膜腺体数量或内膜腺体面积分数而言,子宫内膜样组织的发育与孕激素浓度不成正比。这些结果表明,蜕膜化可能与局部子宫内膜孕激素浓度不相称。值得注意的是,高浓度组的子宫内膜腺体数量增加且出现了致密化,这表明高浓度组的子宫内膜状况可能最有利于提高妊娠率。这些发现表明,可能存在一个用于蜕膜化的“最佳孕激素浓度”,应用该浓度可能会为提高不孕女性的妊娠率带来新策略。