Induction of proteinases in the human preovulatory follicle of the menstrual cycle by human chorionic gonadotropin

Fertil Steril. 2015 Mar;103(3):826-33. doi: 10.1016/j.fertnstert.2014.11.017. Epub 2014 Dec 13.


Objective: To explore the temporal expression in granulosa and theca cells of key members of the MMP and ADAMTS families across the periovulatory period in women to gain insight into their possible roles during ovulation and early luteinization.

Design: Experimental prospective clinical study and laboratory-based investigation.

Setting: University medical center and private IVF center.

Animal and patient(s): Thirty-eight premenopausal women undergoing surgery for tubal ligation and six premenopausal women undergoing assisted reproductive techniques.

Intervention(s): Administration of hCG and harvesting of follicles by laparoscopy and collection of granulosa-lutein cells at oocyte retrieval.

Main outcome measure(s): Expression of mRNA for matrix metalloproteinase (MMPs) and the A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) in human granulosa cells and theca cells collected across the periovulatory period of the menstrual cycle and in cultured granulosa-lutein cells after hCG. Localization of MMPs and ADAMTSs by immunohistochemistry.

Result(s): Expression of MMP1 and MMP19 mRNA increased in both granulosa and theca cells after hCG administration. ADAMTS1 and ADAMTS9 mRNA increased in granulosa cells after hCG treatment, however, thecal cell expression for ADAMTS1 was unchanged, while ADAMTS9 expression was decreased. Expression of MMP8 and MMP13 mRNA was unchanged. Immunohistochemistry confirmed the localization of MMP1, MMP19, ADAMTS1, and ADAMTS9 to the granulosa and thecal cell layers.

Conclusion(s): The collection of the dominant follicle throughout the periovulatory period has allowed the identification of proteolytic remodeling enzymes in the granulosa and theca compartments that may be critically involved in human ovulation. These proteinases may work in concert to regulate breakdown of the follicular wall and release of the oocyte.

Keywords: ADAMTS; Ovulation; granulosa cell; matrix metalloproteinase; theca cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism
  • Cells, Cultured
  • Chorionic Gonadotropin / pharmacology*
  • Enzyme Induction / drug effects
  • Female
  • Follicular Phase* / drug effects
  • Follicular Phase* / genetics
  • Follicular Phase* / metabolism
  • Humans
  • Luteal Cells / drug effects
  • Luteal Cells / metabolism
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Ovarian Follicle / drug effects*
  • Ovarian Follicle / enzymology
  • Ovarian Follicle / metabolism*
  • Peptide Hydrolases / biosynthesis*


  • Chorionic Gonadotropin
  • Peptide Hydrolases
  • ADAM Proteins
  • Matrix Metalloproteinases