Glucose metabolism disorder related to follicular fluid exosomal miR-122-5p in cumulus cells of endometriosis patients.

Abstract

Elevated expression of miR-122-5p in exosomes in the follicular fluid of patients with endometriosis impairs glucose metabolism in cumulus cells and may further impair oocyte quality. Endometriosis (EMs) affects fertility in women of childbearing age in many ways. The underlying mechanisms, including the decrease in oocyte quality, require further investigation. Exosomes, small vesicles responsible for intercellular information exchange, have been found to be involved in many biological events, including follicle development and oocyte meiosis recovery. From the perspective of follicular fluid exosomes, this study aimed to elucidate the mechanisms involved in EMs-related oocyte quality decline. Follicular fluid was collected from three groups of women: the untreated EMs group (EMs_UT), the satisfactorily treated EMs group (EMs_ST), and the control group (Ctrl). Mouse cumulus-oocyte complexes (COCs) were co-cultured with exosomes extracted from follicular fluid during in vitro maturation. Oocyte quality and cumulus cell function were assessed. High-throughput sequencing of miRNA in exosomes was conducted. The function of differentially expressed miRNAs was studied by using SVOG human ovarian granulosa cells transfected with an miRNA mimic and inhibitor. It was found that the follicular fluid exosomes from patients with untreated EMs reduced both the rate of maturation and the quality of mouse oocytes. Overexpression of miR-122-5p in untreated EMs inhibited the translation of key aldolase enzymes related to glucose metabolism and partly impaired glucose metabolism in the cumulus cells of patients with endometriosis. miR-122-5p was also observed to reduce proliferation and increase apoptosis after cell transfection with an miR-122-5p mimic and inhibitor. Further experiments are needed to determine whether there are additional small molecules in the follicular fluid of patients with endometriosis that could be involved in damaging oocyte quality and to identify where harmful substances in follicular fluid exosomes are loaded.