RESUMEN
BACKGROUND/AIM: Age-related decline in the number of ovulations and ovum quality are major causes of female infertility, and stem cells have been reported to be effective in tissue regeneration. However, current therapeutic modalities are inadequate. This study investigated the effects of adipose-derived mesenchymal stem cells (ASCs) on ovarian functions in aged mice. MATERIALS AND METHODS: Following the characterization of ASCs using flow cytometry, the effects of ASCs on the number of ovulations, fertilization rate, and blastocyst-formation rate were investigated. In addition, the number of ovarian follicles and serum anti-Müllerian hormone (AMH) levels were examined. ASCs marked with Kusabira Orange were used to examine the location after cell administration. The quality of ovulated oocytes was analyzed using next-generation RNA sequencing. RESULTS: ASCs showed characteristics of mesenchymal stem cells and were distributed to various organs, including the ovarian stroma. The transplantation resulted in increased number of oocytes and ovulation in the ovaries and increased AMH values. Genetic analysis revealed improved oocyte quality and increased fertilization and blastocyst-formation rates. CONCLUSION: ASC therapy may be effective in improving fertility in older women.
Asunto(s)
Tejido Adiposo , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Oocitos , Ovario , Animales , Femenino , Trasplante de Células Madre Mesenquimatosas/métodos , Ratones , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Tejido Adiposo/citología , Envejecimiento/fisiología , Hormona Antimülleriana/sangre , Hormona Antimülleriana/metabolismo , Folículo Ovárico/metabolismo , Folículo Ovárico/citología , OvulaciónRESUMEN
Many countries, including Japan, are experiencing declining birth rates. Assisted reproductive technologies have consistently demonstrated good results in resolving infertility. Although the development of fertilized eggs into blastocysts has been recognized as a crucial step in assisted reproductive technologies, the involved mechanisms are currently unclear. Here, we established a new culture system for the in vitro development of fertilized eggs into blastocysts. In the Transwell culture system, the rate of blastocysts hatching from fertilized eggs cultured with adipose-derived stem cells (ASCs) was significantly higher than that of blastocysts cultured only with fertilized eggs. Gene ontology analysis revealed that the developed blastocysts displayed essential gene expression patterns in mature blastocysts. Additionally, when cultured with 3rd-passage ASCs, the developed blastocysts expressed the core genes for blastocyst maturation and antioxidant properties compared to those cultured only with fertilized eggs or cultured with 20th-passage ASCs. These results suggest that the Transwell culture system may imitate the in vivo tubal culture state for fertilized eggs. Exosomes derived from stem cells with stemness potential play a powerful role in the development of blastocysts from fertilized eggs. Additionally, the exosomes expressed specific microRNAs; therefore, the Transwell culture system resulted in a higher rate of pregnancy. In future, the extraction of their own extracellular vesicles from the culture medium might contribute to the development of novel assisted reproductive technologies.