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Evidence for the involvement of FXR signaling in ovarian granulosa cell function

Kentaro Takae1, Mizuho Nakata1, Takafumi Watanabe2

  • 1Laboratory of Applied Reproductive Science, Faculty of Agriculture, Shinshu University, Nagano 399-4598, Japan.

The Journal of Reproduction and Development
|November 20, 2018
PubMed

Insights

Farnesoid X receptor (FXR) is present in mouse ovaries, regulating granulosa cell function. FXR signaling impacts genes involved in steroidogenesis and follicle development, suggesting a role in ovarian physiology.

Area of Science:

  • Endocrinology
  • Reproductive Biology
  • Molecular Biology

Background:

  • Farnesoid X receptor (FXR) is a nuclear receptor primarily known for regulating cholesterol, lipid, and glucose metabolism in enterohepatic tissues.
  • FXR's expression and function in reproductive tissues, particularly the ovary, remain largely uncharacterized.
  • Granulosa cells are crucial for ovarian follicle development and function.

Purpose of the Study:

  • To investigate the expression and function of FXR in mouse ovarian granulosa cells.
  • To identify FXR target genes within the ovary.
  • To elucidate the role of FXR signaling in granulosa cell function and steroidogenesis.

Main Methods:

  • In situ hybridization and immunohistochemical staining to determine FXR localization in mouse ovaries.
  • Primary culture of mouse granulosa cells for gene expression analysis.
  • Treatment with FXR agonists and siRNA-mediated gene silencing to assess FXR activity and target gene regulation.
  • Quantitative analysis of gene expression, including steroidogenic enzymes and follicle development markers.

Main Results:

  • FXR expression was detected primarily in secondary and tertiary follicles within the mouse ovary.
  • FXR activation in cultured granulosa cells upregulated SHP and FABP6 expression.
  • FXR knockdown decreased the expression of CYP19a1 and HSD17b1.
  • SHP overexpression reduced StAR, CYP11a1, and HSD3b gene expression.
  • FABP6 modulation affected CYP19a1 and HSD17b1 expression, with overexpression increasing CYP19a1.

Conclusions:

  • FXR signaling is present and active in the mouse ovary.
  • FXR, through its target genes SHP and FABP6, plays a significant role in regulating granulosa cell function.
  • FXR signaling influences key genes involved in steroidogenesis and follicle maturation, indicating a potential role in ovarian physiology.
Keywords:
Farnesoid X receptor (FXR)Granulosa cellOvarySteroidogenesis

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