Potential of thrombospondin-1 in treatment of polycystic ovary syndrome rat model: a preliminary study

Liu, Meimei; Wang, Chao; Zhang, Yuhong; Wang, Rui-Jing; Lu, Xiu-Min; Li, Peiling; Wang, Yuxin; Gong, Pi-Dong; Liu, Ning; Zhang, Ting; Tian, Tingting

doi:10.1080/09513590.2021.1950682

Gynecological Endocrinology

2021

DOI: 10.1080/09513590.2021.1950682

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Potential of thrombospondin-1 in treatment of polycystic ovary syndrome rat model: a preliminary study

Meimei Liu

Chao Wang

Yuhong Zhang

et al.

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2023

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Cited by 2 publications

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Improvement of Inflammation and Abnormal Vascularization by TSP1 Treatment Combined with ADSCs Transplantation in Mice with Induced Polycystic Ovary Syndrome

Ju,

Wang,

Yang

et al. 2023

Advanced Biology

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Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease with a certain degree of chronic inflammation and abnormal ovarian angiogenesis in reproductive women. Mesenchymal stem cells (MSCs) have potent immunomodulatory properties to regulate ovarian function, while thrombospondin 1 (TSP1) improves the abnormal formation of ovarian vessels. The present study investigated the efficacy of the combined use of adipose‐derived mesenchymal stem cells (ADSCs) and TSP1 in PCOS mice. The PCOS model is established using dehydroepiandrosterone (DHEA) by subcutaneous injection. Ovarian apoptosis is assessed using terminal deoxynucleotidyl transferase dUTP nick‐end labeling (TUNEL). Real‐time quantitative PCR (RT‐PCR) and western blotting are used to detect the expression of inflammatory factors and the levels of angiogenesis‐related factors in ovarian tissues. Inflammatory cells count and ovarian angiogenesis are evaluated by immunofluorescence staining. This research shows that TSP1 and ADSCs treatment can significantly reduce the inflammatory state of PCOS mice, relieve the degree of ovarian cell apoptosis, optimize the ovarian histological manifestations, and restore the levels of related hormones. The proportion of CD31‐positive cells in PCOS mice returned to near‐normal levels. The synergistic use of ADSCs and TSP1 therapy can exert a more impressive effect by inhibiting the ovarian inflammatory response and regulating the balance of angiogenesis than the single application in PCOS mice.

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Improvement of Inflammation and Abnormal Vascularization by TSP1 Treatment Combined with ADSCs Transplantation in Mice with Induced Polycystic Ovary Syndrome

Ju,

Wang,

Yang

et al. 2023

Advanced Biology

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Ovarian ERβ cistrome and transcriptome reveal chromatin interaction with LRH-1

Birgersson,

Indukuri,

Lindquist

et al. 2023

BMC Biol

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Background Estrogen receptor beta (ERβ, Esr2) plays a pivotal role in folliculogenesis and ovulation, yet its exact mechanism of action is mainly uncharacterized. Results We here performed ERβ ChIP-sequencing of mouse ovaries followed by complementary RNA-sequencing of wild-type and ERβ knockout ovaries. By integrating the ERβ cistrome and transcriptome, we identified its direct target genes and enriched biological functions in the ovary. This demonstrated its strong impact on genes regulating organism development, cell migration, lipid metabolism, response to hypoxia, and response to estrogen. Cell-type deconvolution analysis of the bulk RNA-seq data revealed a decrease in luteal cells and an increased proportion of theca cells and a specific type of cumulus cells upon ERβ loss. Moreover, we identified a significant overlap with the gene regulatory network of liver receptor homolog 1 (LRH-1, Nr5a2) and showed that ERβ and LRH-1 extensively bound to the same chromatin locations in granulosa cells. Using ChIP-reChIP, we corroborated simultaneous ERβ and LRH-1 co-binding at the ERβ-repressed gene Greb1 but not at the ERβ-upregulated genes Cyp11a1 and Fkbp5. Transactivation assay experimentation further showed that ERβ and LRH-1 can inhibit their respective transcriptional activity at classical response elements. Conclusions By characterizing the genome-wide endogenous ERβ chromatin binding, gene regulations, and extensive crosstalk between ERβ and LRH-1, along with experimental corroborations, our data offer genome-wide mechanistic underpinnings of ovarian physiology and fertility.

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Potential of thrombospondin-1 in treatment of polycystic ovary syndrome rat model: a preliminary study

Cited by 2 publications

References 20 publications

Improvement of Inflammation and Abnormal Vascularization by TSP1 Treatment Combined with ADSCs Transplantation in Mice with Induced Polycystic Ovary Syndrome

Improvement of Inflammation and Abnormal Vascularization by TSP1 Treatment Combined with ADSCs Transplantation in Mice with Induced Polycystic Ovary Syndrome

Ovarian ERβ cistrome and transcriptome reveal chromatin interaction with LRH-1

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