RESUMO
To explore whether granulosa cell (GC)-derived exosomes (GC-Exos) and follicular fluid-derived exosomes (FF-Exos) have functional similarities in follicle development and to establish relevant experiments to validate whether GC-Exos could serve as a potential substitute for follicular fluid-derived exosomes to improve folliculogenesis. GC-Exos were characterized. MicroRNA (miRNA) profiles of exosomes from human GCs and follicular fluid were analyzed in depth. The signature was associated with folliculogenesis, such as phosphatidylinositol 3 kinases-protein kinase B signal pathway, mammalian target of rapamycin signal pathway, mitogen-activated protein kinase signal pathway, Wnt signal pathway, and cyclic adenosine monophosphate signal pathway. A total of five prominent miRNAs were found to regulate the above five signaling pathways. These miRNAs include miRNA-486-5p, miRNA-10b-5p, miRNA-100-5p, miRNA-99a-5p, and miRNA-21-5p. The exosomes from GCs and follicular fluid were investigated to explore the effect on folliculogenesis by injecting exosomes into older mice. The proportion of follicles at each stage is counted to help us understand folliculogenesis. Exosomes derived from GCs were isolated successfully. miRNA profiles demonstrated a remarkable overlap between the miRNA profiles of FF-Exos and GC-Exos. The shared miRNA signature exhibited a positive influence on follicle development and activation. Furthermore, exosomes derived from GCs and follicular fluid promoted folliculogenesis in older female mice. Exosomes derived from GCs had similar miRNA profiles and follicle-promoting functions as follicular fluid exosomes. Consequently, GC-Exos are promising for replacing FF-Exos and developing new commercial reagents to improve female fertility.
Assuntos
Exossomos , Células da Granulosa , MicroRNAs , Folículo Ovariano , Animais , Feminino , Humanos , Camundongos , Exossomos/genética , Exossomos/metabolismo , Líquido Folicular/metabolismo , Células da Granulosa/metabolismo , MicroRNAs/genética , Folículo Ovariano/metabolismo , Transdução de SinaisRESUMO
Although several studies have reported that high maternal BMI could influence the cumulative live birth rate (CLBR) in fresh embryo transfer cycles, the association of BMI with CLBR remains unclear in patients that completed IVF treatment. In this study, we examined the association of maternal BMI with CLBR, including repetitive one oocyte pick-up (OPU) and all fresh and frozen embryo transfer until live birth or embryos were run out. A total of 16,126 patients' data were included in the analysis and were divided into four groups based on BMI. We found that patients' characteristics, embryo parameters, and pregnancy outcomes differed among different BMI groups. Multivariate logistic regression showed that being underweight was associated with a higher possibility of having live birth than the reference group (OR (95% CI) 1.40 (1.22-1.59), P < 0.001), whereas being overweight and obese were associated with a lower possibility of having live birth than the reference group ((OR (95% CI) 0.81 (0.74-0.90), P < 0.001) and (OR (95% CI) 0.68 (0.55-0.85), P < 0.001)). After adjustment for confounding factors, the reference group was associated with a higher possibility of having live birth, with a significant difference found between the obese and reference groups (OR (95% CI) 0.55 (0.43-0.70), P < 0.001). An association was found between CLBR and BMI, indicating that an increase in BMI results in a decline in CLBR. Moreover, the CLBR of patients with different characteristics differed in the various BMI groups. Taken together, our data show that maternal BMI has a significant impact on CLBR.