Micro-RNAs involved in cellular proliferation have altered expression profiles in granulosa of young women with diminished ovarian reserve
The study aims to determine differences in micro-RNA (miRNA) expression in granulosa (GC) and cumulus cells (CC) between young women with diminished ovarian reserve (DOR) or normal ovarian reserve (NOR). Secondary objective was to identify downstream signaling pathways that could ultimately indicate causes of lower developmental competence of oocytes from young women with DOR.
The method of the study is prospective cohort study.
Of the miRNA, 125 are differentially expressed in GC between DOR and NOR. Only nine miRNA were different in CC; therefore, we focused analysis on GC. In DOR GC, miR-100-5p, miR-16-5p, miR-30a-3p, and miR-193a-3p were significantly downregulated, while miR-155-5p, miR-192-5p, miR-128-3p, miR-486-5p, miR130a-3p, miR-92a-3p, miR-17-3p, miR-221-3p, and miR-175p were increased. This pattern predicted higher cell proliferation in the DOR GC. The primary pathways include MAPK, Wnt, and TGFbeta.
The miRNA pattern identified critical functions in cell proliferation and survival associated with DOR. GC in women with DOR seems to respond differently to the LH surge.
KeywordsMicro-RNA Granulosa cells Cumulus cells Diminished ovarian reserve
The research was supported by NIH grant HD082484 awarded to LKM and LKC.
- 9.Paul P, Chakraborty A, Sarkar D, Langthasa M, Rahman M, Bari M, Singha RS, Malakar AK, Chakraborty S. Interplay between miRNAs and human diseases. J Cell Physiol 2017.Google Scholar
- 16.da Silveira JC, Winger QA, Bouma GJ, Carnevale EM. Effects of age on follicular fluid exosomal microRNAs and granulosa cell transforming growth factor-? signalling during follicle development in the mare. Reprod Fertil Dev 2015.Google Scholar
- 20.Santonocito M, Vento M, Guglielmino MR, Battaglia R, Wahlgren J, Ragusa M, et al. Molecular characterization of exosomes and their microRNA cargo in human follicular fluid: bioinformatic analysis reveals that exosomal microRNAs control pathways involved in follicular maturation. Fertil Steril. 2014;102:1751–61. e1751CrossRefPubMedGoogle Scholar
- 23.Sang Q, Yao Z, Wang H, Feng R, Wang H, Zhao X, et al. Identification of microRNAs in human follicular fluid: characterization of microRNAs that govern steroidogenesis in vitro and are associated with polycystic ovary syndrome in vivo. J Clin Endocrinol Metab. 2013;98:3068–79.CrossRefPubMedGoogle Scholar
- 25.La Marca A, Minasi MG, Sighinolfi G, Greco P, Argento C, Grisendi V, et al. Female age, serum antimullerian hormone level, and number of oocytes affect the rate and number of euploid blastocysts in in vitro fertilization/intracytoplasmic sperm injection cycles. Fertil Steril. 2017;108:777–83. e772CrossRefPubMedGoogle Scholar
- 28.Cohen J, Mounsambote L, Prier P, Mathieu D’Argent E, Selleret L, Chabbert-Buffet N, et al. Outcomes of first IVF/ICSI in young women with diminished ovarian reserve. Minerva Ginecol. 2016;Google Scholar
- 31.Andrews S. FastQC: a quality control tool for high throughput sequence data. 2010. Available online at: http://www.bioinformatics.babraham.ac.uk/projects/fastqc.
- 35.Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol. 1995:289–300.Google Scholar
- 45.Baumgarten SC, Armouti M, Ko C, Stocco C. IGF1R Expression in Ovarian Granulosa Cells is Essential for Steroidogenesis, Follicle Survival, and Fertility in Female Mice. Endocrinology 2017.Google Scholar