TY - JOUR
T1 - The endogenous hydrogen sulfide generating system regulates ovulation
AU - Estienne, Anthony
AU - Portela, Valério M.
AU - Choi, Yohan
AU - Zamberlam, Gustavo
AU - Boerboom, Derek
AU - Roussel, Vickie
AU - Meinsohn, Marie Charlotte
AU - Brännström, Mats
AU - Curry, Thomas E.
AU - Jo, Misung
AU - Price, Christopher A.
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
KW - Follicle
KW - Granulosa cells
KW - Ovary
KW - Ovulation
UR - http://www.scopus.com/inward/record.url?scp=85065542276&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065542276&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2019.03.028
DO - 10.1016/j.freeradbiomed.2019.03.028
M3 - Article
C2 - 30930295
AN - SCOPUS:85065542276
SN - 0891-5849
VL - 138
SP - 43
EP - 52
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -