Improved uterine conditions following ovarian transplantation of adipose-derived mesenchymal stem cell conditioned media in rats with letrozole-induced polycystic ovary syndrome: Histomorphometrical, biochemical, and molecular analysis

Regenerative medicine is a new hope for the treatment of diseases such as polycystic ovarian syndrome (PCOS). Due to the beneficial effects of adipose stem cell-derived conditioned media transplantation (ASC-CM) on polycystic ovary phenotypes and also considering the relationship between uterine function and ovarian hormone level, this study, for the first time, evaluates the transplantation of ASC-CM in compared to ASC on the altered state of the uterus, estrogen level as well as its receptors expression in PCOS model. Animals were divided randomly into two groups, including the CMC group and the PCOS group. After PCOS confirmation, the PCOS rats were allocated into four subgroups, including PCOS-Vehicle, PCOS-Media, PCOS-ASC, and PCOS-ASC-CM. After four weeks, the uterus tissues were removed for weighing, histomorphometrical evaluation, and immunoblotting assessments of estrogen receptors (ERα and ERβ). The sera were obtained for estrogen hormone level evaluation. Uterine histopathological conditions, such as marked reductions of the heights of the luminal and glandular epithelial cells as well as altered lining epithelial cells of the lumen and glands, alongside diminished uterine weight and thickness, were observed in the PCOS-V and PCOS-Media groups when compared to those of the CMC group. Additionally, their estrogen levels and ERα and ERβ expression levels decreased. However, ASC-CM administration, compared to ASCs alone, more effectively improved these altered uterine conditions of PCOS rats, resulting in enhanced uterine and endometrial wall thickness, luminal and glandular epithelial cell heights, estrogen levels, and also ESRα and ESRβ mRNA transcripts expression compared to those of the PCOS-V and PCOS-Media groups. So, the transplantation of ASC-CM, compared to ASC, could induce more estrogenic histological changes in the PCOS uterine alterations, which suggests a helpful strategy for improving forgotten uterine status in PCOS phenotypes.