scholarly journals TRIM28-dependent SUMOylation protects the adult ovary from the male pathway

2021 ◽  
Author(s):  
Moïra Rossitto ◽  
Stephanie Dejardin ◽  
Chris M Rands ◽  
Stephanie Legras ◽  
Roberta Migale ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Granulosa Cells ◽  
Sertoli Cells ◽  
Ovary Cell ◽  
Protective Mechanism ◽  
Intermediate Cell ◽  
Post Translational Modification ◽  
Ovarian Granulosa Cells ◽  
Adult Ovary

Gonadal sexual fate in mammals is determined during embryonic development and must be actively maintained in adulthood. Therefore, gonadal sex-specific transcription factors are required to prevent transdifferentiation of gonadal somatic cells to the other sexual fate. Mouse genetic experiments have shown that oestrogen receptor signalling and the transcription factor FOXL2 protect ovarian granulosa cells from transdifferentiation into Sertoli cells, their testicular counterpart. However, the mechanism underlying this protective mechanism is unknown. Here, we show that one post-translational modification (i.e. SUMOylation catalysed by TRIM28) is sufficient to prevent female-to-male sex reversal of the mouse ovary after birth. We found that upon loss of TRIM28 SUMO-E3 ligase activity, ovarian granulosa cells transdifferentiate to Sertoli cells through an intermediate cell type different from gonadal embryonic progenitors. TRIM28 binds to chromatin close to the critical transcription factor FOXL2 to maintain the female pathway through SUMOylation of specific chromatin regions. Therefore, FOXL2 signalling might maintain the adult ovary cell fate via TRIM28-dependent SUMOylation. Improper SUMOylation of chromatin regions in granulosa cells might lead to female reproductive disorders and infertility, the incidence of which is currently increasing.

scholarly journals Author response: The transcription factor FOXL2 mobilizes estrogen signaling to maintain the identity of ovarian granulosa cells

2014 ◽  
Author(s):  
Adrien Georges ◽  
David L'Hôte ◽  
Anne Laure Todeschini ◽  
Aurélie Auguste ◽  
Bérangère Legois ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Granulosa Cells ◽  
Author Response ◽  
Estrogen Signaling ◽  
Ovarian Granulosa Cells

scholarly journals Protective mechanism of FSH against oxidative damage in mouse ovarian granulosa cells by repressing autophagy

Autophagy ◽  
2017 ◽  
Vol 13 (8) ◽  
pp. 1364-1385 ◽  
Author(s):  
Ming Shen ◽  
Yi Jiang ◽  
Zhiqiang Guan ◽  
Yan Cao ◽  
Liechuan Li ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Granulosa Cells ◽  
Protective Mechanism ◽  
Ovarian Granulosa Cells

scholarly journals Ethanol-Induced Mitochondrial Damage in Sertoli Cells is Associated with Parkin Overexpression and Activation of Mitophagy

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 283 ◽  
Author(s):  
Nabil Eid ◽  
Yuko Ito ◽  
Akio Horibe ◽  
Yoshinori Otsuki ◽  
Yoichi Kondo
Keyword(s):  
Transcription Factor ◽  
Sertoli Cells ◽  
Molecular Mechanisms ◽  
Mitochondrial Damage ◽  
Control Group ◽  
Protective Mechanism ◽  
Adult Rats ◽  
Therapeutic Implications ◽  
Protein Levels ◽  
Enhanced Expression

This study was conducted to elucidate the involvement of the PINK1-Parkin pathway in ethanol-induced mitophagy among Sertoli cells (SCs). In the research, adult rats were given intraperitoneal injections of ethanol (5 gm/kg) and sacrificed at various time periods within 24 h. Transmission electron microscopy was applied to reveal enhanced mitochondrial damage in SCs of the ethanol-treated rats (ETRs) in association with a significant increase in numbers of mitophagic vacuoles (mitophagosomes and autolysosomes) in contrast to very low levels in a control group treated with phosphate-buffered saline (PBS). This enhancement was ultra-structurally verified via observation of trapped mitochondria within LC3-labeled membranes, upregulation of LC3 protein levels, colocalization of LC3 and cytochrome c, and reduced expression of mitochondrial proteins. Importantly, Parkin expression was found to be upregulated in ETR SCs, specifically in mitochondria and mitophagosomes in addition to colocalization with PINK1 and pan-cathepsin, indicating augmented mitophagy. Transcription factor EB (TFEB, a transcription factor for autophagy and mitophagy proteins) was also found to be upregulated in nuclei of ETR SCs and associated with enhanced expression of iNOS. Enhanced Parkin-related mitophagy in ETR SCs may be a protective mechanism with therapeutic implications. To the authors’ knowledge, this is the first report demonstrating the ultrastructural characteristics and molecular mechanisms of Parkin-related mitophagy in ETR SCs.

MiR-126* is a novel functional target of transcription factor SMAD4 in ovarian granulosa cells

Gene ◽  
2019 ◽  
Vol 711 ◽  
pp. 143953 ◽  
Author(s):  
Qiqi Li ◽  
Xing Du ◽  
Lu Liu ◽  
Zengxiang Pan ◽  
Shaoxian Cao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Granulosa Cells ◽  
Ovarian Granulosa Cells

cDNA cloning reveals the potential of human ovarian granulosa cells to secrete collagenase inhibitor

1989 ◽  
Vol 120 (3_Suppl) ◽  
pp. S138
Author(s):  
J. FREUDENSTEIN ◽  
J. MUCHA ◽  
G. RAPP ◽  
K. H. SHEIT
Keyword(s):  
Cdna Cloning ◽  
Granulosa Cells ◽  
Ovarian Granulosa Cells ◽  
Collagenase Inhibitor

E-cadherin-catenin complex in the rat ovary: cell-specific expression during folliculogenesis and luteal formation

Reproduction ◽  
2000 ◽  
pp. 375-385 ◽  
Author(s):  
K Sundfeldt ◽  
Y Piontkewitz ◽  
H Billig ◽  
L Hedin
Keyword(s):  
Granulosa Cells ◽  
Interstitial Cells ◽  
Ovary Cell ◽  
Beta Catenin ◽  
Oestrogen Treatment ◽  
Altered Expression ◽  
Preantral Follicles ◽  
Rat Ovary ◽  
E Cadherin ◽  
Cell Cell

The cadherins and their cytoplasmic counterparts, the catenins, form the adherens junctions, which are of importance for tissue integrity and barrier functions. The development and maturation of the ovarian follicle is characterized by structural changes, which require altered expression or function of the components involved in cell-cell contacts. The present study examined the cell-specific localization and temporal expression of epithelial cadherin (E-cadherin) and alpha- and beta-catenin during follicular development, ovulation and corpus luteum formation in the immature gonadotrophin- and oestrogen-stimulated rat ovary. Immunohistochemistry and immunoblotting demonstrated the expression of E-cadherin in theca and interstitial cells of immature ovaries before and after injection of equine chorionic gonadotrophin (eCG). E-cadherin was not detected in granulosa cells, except in the preantral follicles located to the inner region of the ovary. The content of E-cadherin in theca and interstitial cells decreased after an ovulatory dose of hCG. Granulosa cells of apoptotic follicles did not express E-cadherin. Oestrogen treatment (diethylstilboestrol) of immature rats for up to 3 days did not result in a measurable expression of E-cadherin in granulosa cells. alpha- and beta-catenin were expressed in all ovarian compartments. The concentration of beta-catenin was constant during the follicular phase, whereas the content of alpha-catenin decreased in granulosa cells after treatment with diethylstilboestrol or hCG. The expression of alpha-catenin was also reduced in theca and interstitial cells after hCG. alpha- and beta-catenin were present in most ovarian cells at all stages of folliculogenesis. Therefore, the catenins have the potential to associate with different members of the cadherin family and to participate in the regulation of cytoskeletal structures and intracellular signalling. The restricted expression of E-cadherin in granulosa cells of preantral follicles indicates a role in the recruitment of these follicles to subsequent cycles. The specific decrease of alpha-catenin in granulosa cells and the reduction of both alpha-catenin and E-cadherin in theca cells of ovulatory follicles might reflect some of the molecular changes in cell-cell adhesion associated with ovulation and luteinization.

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