The CXCL12-CXCR4 signaling promotes oocyte maturation by regulating cumulus expansion in sheep

Theriogenology. 2018 Feb:107:85-94. doi: 10.1016/j.theriogenology.2017.10.039. Epub 2017 Nov 4.

Abstract

Gonadotropins and growth factors synergistically regulate folliculogenesis and oocyte development. C-X-C motif chemokine 12 (CXCL12) and its receptor CXCR4 are expressed in ovaries of sheep, cattle and other species, however, roles of this multifunctional signal axis in oocyte maturation are not defined. Using sheep as a model, we examined the expression patterns and functions of the CXCL12-CXCR4 axis during oocyte maturation. CXCL12 and CXCR4 mRNA and protein were present in oocytes and granulosa cells. Relative abundance of CXCR4 transcript was controlled by epidermal growth factor (EGF). Transient inhibition of CXCR4 suppressed oocyte nuclear maturation while supplementing recombination CXCL12 significantly increased percent of oocyte undergone metaphase I phase. Inhibition of CXCR4 function decreased cumulus expansion growth rate. Furthermore, granulosa cell migration was impaired and expression of hyaluronan synthase 2 (HAS2) and hyaluronan binding protein tumor necrosis factor-alpha-induced protein 6 (TNFAIP6) were downregulated by CXCR4 inhibition. These findings revealed a novel role of the CXCL12-CXCR4 signaling in oocyte development in sheep.

Keywords: CXCL12; CXCR4; In vitro maturation; Oocyte; Ovary; Sheep.

MeSH terms

  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / metabolism*
  • Cumulus Cells / physiology*
  • Female
  • Gene Expression Regulation
  • Granulosa Cells / physiology
  • Hyaluronan Synthases / genetics
  • Hyaluronan Synthases / metabolism
  • Oocytes / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*
  • Sheep*
  • Signal Transduction / physiology

Substances

  • Cell Adhesion Molecules
  • Chemokine CXCL12
  • RNA, Messenger
  • Receptors, CXCR4
  • Hyaluronan Synthases