PATL2 regulated the apoptosis of ovarian granulosa cells in patients with PCOS

Peng, S; Wu, Qiongfang; Xie, Qiang; Tan, Jun; Shu, Kuanyong

doi:10.1080/09513590.2021.1928066

Cited by 17 publications

(12 citation statements)

References 27 publications

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“…In this study, we first proposed that the mature adipocytes could inhibit the viability of CC cells and promote the apoptosis when compared with preadipocytes. Some studies believed that PCOS patients have the phenomenon of reduced apoptosis of granulosa cells (29), and the programmed apoptosis of granulosa cells is shown to be necessary for follicular maturation (30). However, in the current study, the apoptosis rate increased after treatment with adipocytes extracellular vesicles when compared with the control, which means that even if the programmed apoptosis of granulosa cells in the body is cycle specific, the apoptosis rate is increased when treated with the adipocytes extracellular vesicles.…”

Section: Discussioncontrasting

confidence: 78%

Adipocytes-Derived Extracellular Vesicle-miR-26b Promotes Apoptosis of Cumulus Cells and Induces Polycystic Ovary Syndrome

Zhou

et al. 2022

Front. Endocrinol.

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BackgroundPolycystic ovary syndrome (PCOS) is a refractory reproductive disease and also a kind of endocrine and metabolic disease. Adipocyte cells can produce a mass of extracellular vesicles and orchestrate the status of other types cells. The objective of this study was to determine the effects of adipocyte-derived extracellular vesicles-miR-26b on cumulus cells (CCs) and development of PCOS.MethodsThe crosstalk mediated by extracellular vesicle-miR-26b between adipocytes and CCs was determined in CC cells co-cultured with mature adipocytes or incubated with extracellular vesicle isolated from mature adipocytes. CCK-8 assay and flow cytometry were conducted in CCs treated with or without extracellular vesicles; microRNA (miRNA) sequencing was conducted for clarifying the key molecular. Hormone levels and ovary ovulation ability were conducted with animal experiment.ResultsThe results revealed that miR-26b was upregulated in extracellular vesicles derived from mature adipocytes. Adipocyte-derived extracellular vesicles inhibited viability and promoted apoptosis in CCs via targeting JAG1. Furthermore, extracellular vesicles derived from mature adipocyte disrupted the ovary ovulation and impaired the hormone levels.ConclusionsThese results identify a novel signaling pathway that adipocytes-derived extracellular vesicles-miR-26b promotes cell apoptosis in CCs and disrupted the ovary ovulation in the development of PCOS. The study indicates that adipose tissue-derived extracellular vesicles-miR-26b may play a key role in the PCOS and also provides insight into developing new therapeutic strategies for PCOS.

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Section: Discussioncontrasting

confidence: 78%

Adipocytes-Derived Extracellular Vesicle-miR-26b Promotes Apoptosis of Cumulus Cells and Induces Polycystic Ovary Syndrome

Zhou

et al. 2022

Front. Endocrinol.

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“…One of the pathological features of PCOS is abnormal follicular development. The augmented apoptosis of granulosa cells may have a key role in the pathogenesis of PCOS ( 57 , 58 ). Sphingosine could inhibit cell growth and induce cell apoptosis ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

Brown Adipose Transplantation Improves Polycystic Ovary Syndrome-Involved Metabolome Remodeling

et al. 2021

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Polycystic ovary syndrome (PCOS) is a complex reproductive, endocrine, and metabolic disorder in reproductive-age women. In order to explore the active metabolites of brown adipose tissue (BAT) transplantation in improving the reproductive and metabolic phenotypes in a PCOS rat model, the metabolites in the recipient’s BAT were explored using the liquid chromatography–mass spectrometry technique. In total, 9 upregulated and 13 downregulated metabolites were identified. They were roughly categorized into 12 distinct classes, mainly including glycerophosphoinositols, glycerophosphocholines, and sphingolipids. Ingenuity pathway analysis predicted that these differentially metabolites mainly target the PI3K/AKT, MAPK, and Wnt signaling pathways, which are closely associated with PCOS. Furthermore, one of these differential metabolites, sphingosine belonging to sphingolipids, was randomly selected for further experiments on a human granulosa-like tumor cell line (KGN). It significantly accelerated the apoptosis of KGN cells induced by dihydrotestosterone. Based on these findings, we speculated that metabolome changes are an important process for BAT transplantation in improving PCOS. It might be a novel therapeutic target for PCOS treatment.

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“…There is evidence that the rate of granular cell apoptosis is significantly increased in the antral follicles of women with PCOS compared to normal controls ( 40 , 41 ). Apoptosis of follicular granulosa cells may therefore also be involved in the abnormal development of follicles associated with PCOS ( 42 ). PCOS is an inflammatory disease characterized by persistent nonspecific low-grade inflammation ( 43 , 44 ).…”

Section: Discussionmentioning

confidence: 99%

The PNA mouse may be the best animal model of polycystic ovary syndrome

et al. 2022

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Polycystic ovary syndrome (PCOS) exerts negative effects on females of childbearing age. It is important to identify more suitable models for fundamental research on PCOS. We evaluated animal models from a novel perspective with the aim of helping researchers select the best model for PCOS. RNA sequencing was performed to investigate the mRNA expression profiles in the ovarian tissues of mice with dehydroepiandrosterone (DHEA) plus high-fat diet (HFD)-induced PCOS. Meanwhile, 14 datasets were obtained from the Gene Expression Omnibus (GEO), including eight studies on humans, three on rats and three on mice, and genes associated with PCOS were obtained from the PCOSKB website. We compared the consistency of each animal model and human PCOS in terms of DEGs and pathway enrichment analysis results. There were 239 DEGs shared between prenatally androgenized (PNA) mice and PCOS patients. Moreover, 1113 genes associated with PCOS from the PCOSKB website were identified among the DEGs of PNA mice. A total of 134 GO and KEGG pathways were shared between PNA mice and PCOS patients. These findings suggest that the PNA mouse model is the best animal model to simulate PCOS.

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PATL2 regulated the apoptosis of ovarian granulosa cells in patients with PCOS

Cited by 17 publications

References 27 publications

Adipocytes-Derived Extracellular Vesicle-miR-26b Promotes Apoptosis of Cumulus Cells and Induces Polycystic Ovary Syndrome

Adipocytes-Derived Extracellular Vesicle-miR-26b Promotes Apoptosis of Cumulus Cells and Induces Polycystic Ovary Syndrome

Brown Adipose Transplantation Improves Polycystic Ovary Syndrome-Involved Metabolome Remodeling

The PNA mouse may be the best animal model of polycystic ovary syndrome

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