Granulosa-Lutein Cell Sirtuin Gene Expression Profiles Differ between Normal Donors and Infertile Women

Abstract

Sirtuins are a family of deacetylases that modify structural proteins, metabolic enzymes, and histones to change cellular protein localization and function. In mammals, there are seven sirtuins involved in processes like oxidative stress or metabolic homeostasis associated with aging, degeneration or cancer. We studied gene expression of sirtuins by qRT-PCR in human mural granulosa-lutein cells (hGL) from IVF patients in different infertility diagnostic groups and in oocyte donors (OD; control group). Study 1: sirtuins genes’ expression levels and correlations with age and IVF parameters in women with no ovarian factor. We found significantly higher expression levels of SIRT1, SIRT2 and SIRT5 in patients ≥40 years old than in OD and in women between 27 and 39 years old with tubal or male factor, and no ovarian factor (NOF). Only SIRT2, SIRT5 and SIRT7 expression correlated with age. Study 2: sirtuin genes’ expression in women poor responders (PR), endometriosis (EM) and polycystic ovarian syndrome. Compared to NOF controls, we found higher SIRT2 gene expression in all diagnostic groups while SIRT3, SIRT5, SIRT6 and SIRT7 expression were higher only in PR. Related to clinical parameters SIRT1, SIRT6 and SIRT7 correlate positively with FSH and LH doses administered in EM patients. The number of mature oocytes retrieved in PR is positively correlated with the expression levels of SIRT3, SIRT4 and SIRT5. These data suggest that cellular physiopathology in PR’s follicle may be associated with cumulative DNA damage, indicating that further studies are necessary.

Establishment, immunological analysis, and drug prediction of a prognostic signature of ovarian cancer related to histone acetylation

“…HDAC4 and HDAC10 are Class II HDACs, which are associated with proliferation, migration, and invasion of a variety of cancers ( Cai et al, 2018 ; Cheng et al, 2021 ). SIRT5 is a Class III HDAC that is involved in oxidative stress or metabolic homeostasis related to aging, degeneration, or cancer ( Gonzalez-Fernandez et al, 2019 ). Relevant studies revealed that SIRT5 can promote autophagy of gastric cancer cells, and SIRT5 can inhibit peroxisome-induced oxidative stress, thus protecting the liver and inhibiting the development of hepatoma cells ( Chen et al, 2018 ; Gu et al, 2021 ).…”

SIRT7 in the aging process

“…As feedback, TGF-β signaling antagonizes SIRT7 expression by causing SMAD3/4 to recruit HDAC8 to the SIRT7 promoter and thus chromatin to be remodeled through H4 deacetylation [ 102 , 103 ]. Meanwhile, SIRT7 expression in granulosa-lutein cells from women without ovarian factor was higher with increasing age and was significantly higher in women who responded poorly to in vitro fertilization (IVF) [ 104 ]. Regarding the immune system, SIRT7 silencing reduced lipopolysaccharide (LPS)-induced pro-inflammatory effects and induced an endomesenchymal transition that increased endothelial barrier permeability.…”

Hypoxia: Role of SIRT1 and the protective effect of resveratrol in ovarian function

“… 47 , 48 , 49 The presence of all sirtuins has been confirmed in granulosa cells (GCs) and human ovarian granulosa‐like tumor (KGN) cells. 50 …”