SOD2 deficiency-induced oxidative stress attenuates steroidogenesis in mouse ovarian granulosa cells.


Journal

Molecular and cellular endocrinology
ISSN: 1872-8057
Titre abrégé: Mol Cell Endocrinol
Pays: Ireland
ID NLM: 7500844

Informations de publication

Date de publication:
01 01 2021
Historique:
received: 07 11 2019
revised: 27 05 2020
accepted: 01 06 2020
pubmed: 28 7 2020
medline: 28 7 2021
entrez: 28 7 2020
Statut: ppublish

Résumé

This study investigated the effects of SOD2 (MnSOD)-deficiency-induced excessive oxidative stress on ovarian steroidogenesis in vivo and isolated and cultured granulosa cells using WT and Sod2+/- mice. Basal and 48 h eCG-stimulated plasma progesterone levels were decreased ~50% in female Sod2+/- mice, whereas plasma progesterone levels were decreased ~70% in Sod2+/- mice after sequential stimulation with eCG followed by hCG. Sod2+/- deficiency caused about 50% reduction in SOD2 activity in granulosa cells. SOD2-deficiency also caused a marked reduction in progestins and estradiol in isolated granulosa cells. qRT-PCR measurements indicated that the mRNA expression levels of StAR protein and steroidogenic enzymes are decreased in the ovaries of Sod2+/- mice. Further studies showed a defect in the movement of mobilized cytosolic cholesterol to mitochondria. The ovarian membrane from Sod2+/- mice showed higher susceptibility to lipid peroxidation. These data indicates that SOD2-deficiency induced oxidative stress inhibits ovarian granulosa cell steroidogenesis primarily by interfering with cholesterol transport to mitochondria and attenuating the expression of Star protein gene and key steroidogenic enzyme genes.

Identifiants

pubmed: 32717420
pii: S0303-7207(20)30188-X
doi: 10.1016/j.mce.2020.110888
pmc: PMC8011630
mid: NIHMS1678509
pii:
doi:

Substances chimiques

Antioxidants 0
Hydroxycholesterols 0
Steroids 0
22-hydroxycholesterol 17711-16-9
Progesterone 4G7DS2Q64Y
Estradiol 4TI98Z838E
Catalase EC 1.11.1.6
Glutathione Peroxidase EC 1.11.1.9
Superoxide Dismutase EC 1.15.1.1
superoxide dismutase 2 EC 1.15.1.1

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

110888

Subventions

Organisme : BLRD VA
ID : I01 BX000398
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK116074
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

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Auteurs

Syed Kashif Zaidi (SK)

Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA; Division of Endocrinology, Gerontology and Metabolism, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Wen-Jun Shen (WJ)

Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA; Division of Endocrinology, Gerontology and Metabolism, Stanford University School of Medicine, Stanford, CA, 94305, USA. Electronic address: wenjun@stanford.edu.

Yuan Cortez (Y)

Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA.

Stefanie Bittner (S)

Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA.

Alex Bittner (A)

Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA.

Sara Arshad (S)

Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA; Division of Endocrinology, Gerontology and Metabolism, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Ting-Ting Huang (TT)

Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Fredric B Kraemer (FB)

Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA; Division of Endocrinology, Gerontology and Metabolism, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Salman Azhar (S)

Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA; Division of Endocrinology, Gerontology and Metabolism, Stanford University School of Medicine, Stanford, CA, 94305, USA. Electronic address: salman.azhar@va.gov.

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Classifications MeSH