The endogenous hydrogen sulfide generating system regulates ovulation

Anthony Estienne, Valério M. Portela, Yohan Choi, Gustavo Zamberlam, Derek Boerboom, Vickie Roussel, Marie Charlotte Meinsohn, Mats Brännström, Thomas E. Curry, Misung Jo, Christopher A. Price

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The generation of free-radicals such as nitric oxide has been implicated in the regulation of ovarian function, including ovulation. Tissues that generate nitric oxide typically generate another free-radical gas, hydrogen sulfide (H2S), although little is known about the role of H2S in ovarian function. The hypothesis of this study was that H2S regulates ovulation. Treatment with luteinizing hormone (LH)increased the levels of mRNA and protein of the H2S generating enzyme cystathionine γ-lyase (CTH)in granulosa cells of mice and humans in vivo and in vitro. Pharmacological inhibition of H2S generating enzymes reduced the number of follicles ovulating in mice in vivo and in vitro, and this inhibitory action was reversed by cotreatment with a H2S donor. Addition of a H2S donor to cultured mouse granulosa cells increased basal and LH-dependent abundance of mRNA encoding amphiregulin, betacellulin and tumor necrosis alpha induced protein 6, proteins important for cumulus expansion and follicle rupture. Inhibition of CTH activity reduced abundance of mRNA encoding matrix metalloproteinase-2 and -9 and tissue-type plasminogen activator, and cotreatment with the H2S donor increased the levels of these mRNA above those stimulated by LH alone. We conclude that the H2S generating system plays an important role in the propagation of the preovulatory cascade and rupture of the follicle at ovulation.

Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalFree Radical Biology and Medicine
Volume138
DOIs
StatePublished - Jul 2019

Bibliographical note

Funding Information:
We are grateful to Dr A.F. Parlow and National Hormone & Peptide Program, NIDDK for ovine FSH and LH, to Dr Lisa Mehlmann for assistance with in-vitro follicle culture, to Drs Curtis McCloskey and Barbara C. Vanderhyden for assistance with intra-bursal injections, and to Morad Ben Koura, Alix Barbe and Esdras Correa for their technical support. This work was supported by NSERC (to CAP) and NIH ( P01HD71875 to MB, TEC, MJ) and VMP was supported by a scholarship from CNPq .

Funding Information:
We are grateful to Dr A.F. Parlow and National Hormone & Peptide Program, NIDDK for ovine FSH and LH, to Dr Lisa Mehlmann for assistance with in-vitro follicle culture, to Drs Curtis McCloskey and Barbara C. Vanderhyden for assistance with intra-bursal injections, and to Morad Ben Koura, Alix Barbe and Esdras Correa for their technical support. This work was supported by NSERC (to CAP)and NIH (P01HD71875 to MB, TEC, MJ)and VMP was supported by a scholarship from CNPq.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • Follicle
  • Granulosa cells
  • Ovary
  • Ovulation

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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