Recombinant Anti-Müllerian Hormone (rAMH) for Stalling In Vitro Granulosa Cell Replication

Reprod Sci. 2020 Oct;27(10):1873-1878. doi: 10.1007/s43032-020-00206-6. Epub 2020 Jul 2.

Abstract

To investigate whether recombinant AMH (rAMH) is able to decrease cellular proliferation/apoptosis in luteinized granulosa cells (GCs) through hormonal regulation, a primary culture of GCs was established from GCs obtained at time of oocyte retrieval from follicular fluid of 3 patients. Cells were seeded in well cell culture plates at a density of 100,000 cells/well in medium and treated with rAMH 20 ng/ml (rAMH group), or phosphate-buffered saline (PBS-control group), for 24 h. Total RNA was extracted from all cells, followed by cDNA synthesis and real-time RT-PCR to quantify the expression levels of AMH, AMH-R2, FSH-R, inhibin B, cell proliferation (Ki67), and apoptosis (Caspase 3). We used independent sample t test (SPSS v25) and a p < 0.05 significance. Cellular expressions of AMH, AMH-R2, FSH-R, and inhibin B were reduced greater than 50% in the rAMH group, compared with that of the the control group (p ≤ 0.005 for all). Ki67 and Caspase3 were also reduced greater than 30% in the rAMH group (p ≤ 0.001 for both). Our findings show a direct inhibitory effect of AMH on luteinized GCs' expression of the major regulatory hormones, in addition to a significant decrease in markers of cell proliferation and apoptosis. These results confirm the inhibitory effects of AMH on follicular development.

Keywords: Anti-Müllerian hormone; Cell proliferation; Granulosa cells; Recombinant.

MeSH terms

  • Anti-Mullerian Hormone / metabolism
  • Anti-Mullerian Hormone / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Proliferation / drug effects*
  • Female
  • Follicular Fluid
  • Granulosa Cells / cytology
  • Granulosa Cells / drug effects*
  • Humans
  • Inhibins / metabolism
  • Oocyte Retrieval
  • Receptors, FSH / metabolism
  • Receptors, Peptide / metabolism
  • Receptors, Transforming Growth Factor beta / metabolism
  • Recombinant Proteins / pharmacology*

Substances

  • Receptors, FSH
  • Receptors, Peptide
  • Receptors, Transforming Growth Factor beta
  • Recombinant Proteins
  • anti-Mullerian hormone receptor
  • inhibin B
  • Inhibins
  • Anti-Mullerian Hormone
  • Caspase 3