Abnormal expression levels of BMP15/Smad1 are associated with granulosa cell apoptosis in patients with polycystic ovary syndrome

Mol Med Rep. 2017 Dec;16(6):8231-8236. doi: 10.3892/mmr.2017.7658. Epub 2017 Sep 28.

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects reproductive dysfunction and metabolism in women of childbearing age. An increasing number of studies have suggested that the bone morphogenetic protein 15 (BMP15) signalling pathway serves an important role in the pathogenesis of PCOS; however, the full mechanism remains unknown. The present study revealed that intrinsic follicular dysplasia may be associated with regulation disorders of ovarian granulosa cell apoptosis. Compared with the control group, body mass index, luteinising hormone and testosterone levels were significantly increased (P<0.05). The percentage of S phase cells was significantly higher, cells in G2/M phase cells was significantly lower, and cells undergoing apoptosis was significantly higher in the PCOS group compared with the control group (P<0.05). The expression levels of B‑cell lymphoma 2 was significantly decreased in granulosa cells of PCOS group, whereas the expression of caspase‑3 was higher than the control group (P<0.05). The rate of apoptosis of granulosa cells was measured by a terminal deoxynucleotide transferase dUTP nick‑end labelling assay. The relative mRNA expression levels of BMP receptor 2 and SMAD1 were significantly decreased in granulosa cells in the PCOS group compared with the control (P<0.05). In addition, the expression of BMP15 in follicular fluid and Smad1 in granulosa cells was significantly decreased in the PCOS group compared with the control (P<0.05). The data suggested that the BMP15/Smad1 signalling pathway may be involved in granulosa cell apoptosis, and may be a target for clinical treatment for PCOS.

MeSH terms

  • Adult
  • Apoptosis / genetics*
  • Biomarkers
  • Bone Morphogenetic Protein 15 / genetics*
  • Bone Morphogenetic Protein 15 / metabolism
  • Bone Morphogenetic Protein Receptors, Type II / genetics
  • Bone Morphogenetic Protein Receptors, Type II / metabolism
  • Case-Control Studies
  • Female
  • Fertilization
  • Gene Expression Regulation*
  • Granulosa Cells / metabolism*
  • Humans
  • Polycystic Ovary Syndrome / genetics*
  • Polycystic Ovary Syndrome / metabolism
  • Smad1 Protein / genetics*
  • Smad1 Protein / metabolism

Substances

  • Biomarkers
  • Bone Morphogenetic Protein 15
  • SMAD1 protein, human
  • Smad1 Protein
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II