Single-nucleus RNA Sequencing reveals the mechanism of cigarette smoke exposure on diminished ovarian reserve in mice

Li, Fang; Wang, Ying; Xu, Mengting; Hu, Nengyin; Jiang, Miao; Zhao, Yu; Wang, Lili

doi:10.1016/j.ecoenv.2022.114093

Cited by 10 publications

(6 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…WNT10B was specifically expressed only in the granulosa cells, and WNT signaling pathway genes were enriched. Cigarette smoke increased the expression of WNT10B mRNA ( Li F. et al, 2022 ). Others have identified WNT10B expression in the full-grown oocyte, ovulated oocyte, zygote, and two-cell stage embryo ( Harwood et al, 2008 ).…”

Section: Wnt10b and The Ovarymentioning

confidence: 99%

The role of WNT10B in physiology and disease: A 10-year update

Perkins

Singh

Abell

et al. 2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

WNT10B, a member of the WNT family of secreted glycoproteins, activates the WNT/β-catenin signaling cascade to control proliferation, stemness, pluripotency, and cell fate decisions. WNT10B plays roles in many tissues, including bone, adipocytes, skin, hair, muscle, placenta, and the immune system. Aberrant WNT10B signaling leads to several diseases, such as osteoporosis, obesity, split-hand/foot malformation (SHFM), fibrosis, dental anomalies, and cancer. We reviewed WNT10B a decade ago, and here we provide a comprehensive update to the field. Novel research on WNT10B has expanded to many more tissues and diseases. WNT10B polymorphisms and mutations correlate with many phenotypes, including bone mineral density, obesity, pig litter size, dog elbow dysplasia, and cow body size. In addition, the field has focused on the regulation of WNT10B using upstream mediators, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). We also discussed the therapeutic implications of WNT10B regulation. In summary, research conducted during 2012–2022 revealed several new, diverse functions in the role of WNT10B in physiology and disease.

show abstract

Section: Wnt10b and The Ovarymentioning

confidence: 99%

The role of WNT10B in physiology and disease: A 10-year update

Perkins

Singh

Abell

et al. 2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…When SLC7A11, the major functional subunit of system Xc − , is deficient or has reduced activity, GSH synthesis is reduced, causing reduced expression and activity of GPX4, resulting in the inability of cells to effectively scavenge lipid peroxides, and finally oxidative damage to the cell membrane, leading to cell ferroptosis 42 . Previous studies have reported a correlation between GSH, GPX4 and ovarian dysfunction; however, few studies have focused on the correlation between SLC7A11 and POI [43][44][45][46] . Therefore, we mainly selected SLC7A11 to further validate the association of POI and ferroptosis, but we still validated the expression of GPX4 in animal experiments.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of ferroptosis in a rat model of premature ovarian insufficiency induced by cisplatin

Cheng

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Ferroptosis is widely present in fibrosis-related diseases. The basic pathology of premature ovarian insufficiency (POI) involves ovarian tissue fibrosis, and there are currently fewer relevant studies addressing the association between ferroptosis and POI. This study aimed to demonstrate that ferroptosis induced by cisplatin (CDDP) caused ovarian tissue fibrosis, leading to POI. Vitamin E (VE), a ferroptosis inhibitor, could repair damaged ovarian function. CDDP was used to establish a rat model of POI, and VE was administered to reverse the reproductive toxicity of CDDP. Ovarian function was assessed by histological section staining, follicle counts, sex hormone levels, as well as fertility assays. The extent of ferroptosis was assessed by transmission electron microscopy (TEM), malondialdehyde (MDA), Perls staining. CCK-8, Ethynyl-2-Deoxyuridine (EdU), and scratch assays were used to determine the effect of CDDP and VE on ovarian granulosa cell (GC) viability. Western blot, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were performed to evaluate ferroptosis-related molecular changes. Our results showed that CDDP caused follicle development disorders and ovarian tissue fibrosis, the levels of sex hormones suggested impaired ovarian function, and VE could reverse the reproductive toxicity of CDDP. The results of TEM, MDA and Perls staining suggested that the typical mitochondrial signature of ferroptosis was altered in ovarian GCs from the CDDP group, with significantly higher levels of lipid peroxidation and significant iron deposition in ovarian tissue, whereas VE mitigated the extent of ferroptosis. Molecular experiments then confirmed that the ferroptosis-related molecules acetyl CoA synthetase long chain family member 4 (ACSl4), 15-lipoxygenase-1 (ALOX15), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were differentially expressed in each group. In summary, our study preliminarily demonstrated that CDDP may promote GCs to undergo ferroptosis, cause follicle development disorders, ovarian tissue fibrosis, and induce POI by regulating the expression of ACSl4, ALOX15, SLC7A11, and GPX4, while VE improved impaired ovarian function.

show abstract

“…Meanwhile, ACSl4 promotes sensitivity to ferroptosis by shaping cellular lipid components [ 42 ]. The GPX4 is an important factor in ovarian ultrastructural changes [ 43 ] and a potential target for treating ovarian clear cell carcinoma [ 44 ]. Peroxiredoxin 2 (PRDX2) and peroxiredoxin 4 (PRDX4), the member of the PRDX family, are vital antioxidants in cells.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiling of human granulosa cells between women with advanced maternal age with different ovarian reserve

Jia,

Li,

Zhou

et al. 2023

J Assist Reprod Genet

View full text Add to dashboard Cite

Background Age-related diminished ovarian reserve (DOR) is not absolute. Some advanced maternal age (AMA) still have normal ovarian reserve (NOR) and often show better pregnancy outcomes. Exploring the transcriptomic profile of granulosa cells (GCs) in AMA could lead to new ideas for mitigating age-related diminished ovarian reserve. Aim This study aimed to analyze the transcriptomic profile of GCs in AMA with different ovarian reserve. Results In total, 6273 statistically significant differential expression genes (DEGs) (|log2fc|> 1, q < 0.05) were screened from the two groups, among which 3436 genes were upregulated, and 2837 genes were downregulated in the DOR group. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the potential functions of dysregulated genes in AMA with DOR or NOR were predicted. The GO enrichment analysis revealed that the DEGs were mainly enriched in obsolete oxidation–reduction process, mitochondrion, metal ion binding, ATP binding, etc. The KEGG pathway enrichment analysis revealed that the above-mentioned DEGs were mainly enriched in ferroptosis, regulation of actin cytoskeleton, oxidative phosphorylation, etc. Meanwhile, verification of the mRNA expression levels of DEGs revealed the possible involvement of “ferroptosis” in age-related diminished ovarian reserve. Conclusions From a new clinical perspective, we presented the first data showing the transcriptomic profile in GCs between AMA with different ovarian reserve. At the same time, we identified the role of ferroptosis in the GCs of AMA, providing a new biological basis for studying ovarian aging and improving pregnancy outcomes of AMA.

show abstract

Single-nucleus RNA Sequencing reveals the mechanism of cigarette smoke exposure on diminished ovarian reserve in mice

Cited by 10 publications

References 59 publications

The role of WNT10B in physiology and disease: A 10-year update

The role of WNT10B in physiology and disease: A 10-year update

Mechanism of ferroptosis in a rat model of premature ovarian insufficiency induced by cisplatin

Transcriptomic profiling of human granulosa cells between women with advanced maternal age with different ovarian reserve

Contact Info

Product

Resources

About