Clin Exp Reprod Med.  2025 Mar;52(1):44-55. 10.5653/cerm.2024.07094.

Serum miR-329-3p as a potential biomarker for poor ovarian response in an in vitro fertilization

Affiliations
  • 1Department of Biomedical Science, Institute of Reproductive Medicine, College of Life Science, CHA University, Seongnam, Republic of Korea
  • 2CHA Fertility Center Gangnam, CHA University School of Medicine, Seoul, Republic of Korea
  • 3Department of Obstetrics & Gynecology, CHA Fertility Center Seoul Station, CHA University School of Medicine, Seoul, Republic of Korea
  • 4CHAYON Laboratories Inc., Seoul, Republic of Korea
  • 5Department of Obstetrics & Gynecology, CHA Fertility Center Daegu, CHA University School of Medicine, Daegu, Republic of Korea

Abstract


Objective
Several miRNAs have been identified as differentially expressed in patients with poor ovarian response (POR) compared to those with normal responses. This study aims to assess the potential of serum miR-329-3p as a biomarker for diagnosing POR.
Methods
We conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to confirm the target genes of miR-329-3p. KGN cells were transfected with both miR-329-3p mimic and inhibitor to assess the differential expression of these target genes. In accordance with the Bologna criteria, we enrolled 16 control patients and 16 patients with POR. We collected patient samples, including serum from day 2 and the human chorionic gonadotropin (hCG) day, as well as granulosa and cumulus cells, to validate the expression of miR-329-3p using quantitative real-time polymerase chain reaction.
Results
KEGG pathway analysis revealed that miR-329-3p targeted adenylyl cyclase 9 (ADCY9) and protein kinase A subunit beta (PRKACB), both of which are involved in ovarian steroidogenesis. In KGN cells treated with a miR-329-3p mimic, ADCY9 and PRKACB expression levels were significantly reduced (p<0.05). Elevated levels of miR-329-3p suppressed aromatase expression and 17β-estradiol production by modulating ADCY9 and PRKACB in KGN cells. These effects were also observed in POR patients. Follicle-stimulating hormone receptor (FSHR) expression was diminished in the granulosa cells of POR patients. On day 2, on hCG day, and in granulosa cells, miR-329-3p exhibited high expression levels in the serum of POR patients.
Conclusion
miR-329-3p exhibited increased expression in granulosa cells and in the sera of POR patients. Consequently, we propose that miR-329-3p may be a potential biomarker for the diagnosis of POR.

Keyword

Biomarkers; Controlled ovarian hyperstimulation; MicroRNAs; miR-329-3p; Poor ovarian response; Receptors, FSH
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