generation-mouse-artificial-decidualization-model-with-ovariectomy

Generation of a Mouse Artificial Decidualization Model with Ovariectomy for Endometrial Decidualization Research

Endometrial decidualization is a unique differentiation process of the endometrium, closely related to menstruation and pregnancy. Impairment of ...

mitochondrial-transfer-from-mouse-adipose-derived-mesenchymal-stem

Mitochondrial Transfer from Mouse Adipose-Derived Mesenchymal Stem Cells into Aged Mouse Oocytes

Due to the decline in the quantity and quality of oocytes related to age, the fertility of women over 35 years of age has declined sharply. The molecular ...

isolation-culture-three-kinds-umbilical-cord-mesenchymal-stem

Isolation and Culture of Three Kinds of Umbilical Cord Mesenchymal Stem Cells

Umbilical cord mesenchymal stem cells (UC-MSCs) are an important cell source for regenerative medicine. UC-MSCs can be isolated from the umbilical cord ...

Nanjing University Medical School

The Affiliated Drum Tower Hospital of Nanjing University Medical School

Nanjing Medical University

Nanjing University

Premature ovarian failure (POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study, umbilical cord mesenchymal stem cells on a collagen scaffold (collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.

Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility.

Female fertility declines dramatically over the age of 35 due to age-related decreases in oocyte quality and quantity. Although mitochondrial transfer promises to be a technology that can improve the quality of such age-impaired oocytes, the ideal mitochondrial donor remains elusive. In the present study, we aimed to identify whether aged adipose-derived stem cells constitute an excellent mitochondrial donor that would improve the quality of aged mouse oocytes. We showed that aging significantly impaired the mitochondrial function in mouse oocytes, but did not significantly affect the mitochondrial function of adipose-derived stem cells. However, the mitochondrial transfer from aged adipose-derived stem cells did not mitigate the poor fertilization and embryonic development rates of aged oocytes.

Mitochondrial transfer from aged adipose-derived stem cells does not improve the quality of aged oocytes in C57BL/6 mice.

Premature ovarian failure (POF) is a refractory disease; one of the most important goals of treatment is to improve fertility. In the study, collagen scaffold loaded with human umbilical cord-derived mesenchymal stem cells (collagen/UC-MSCs) transplantation in POF mice preserved ovarian function, as supported by increased estrogen (E) and anti-Mullerian hormone (AMH) levels, increased ovarian volume, and an increased number of antral follicles. Immunohistochemistry results of Ki67 indicated transplantation of collagen/UC-MSCs promoted granulosa cell proliferation, which is crucial to oocyte maturation and follicular development. Additionally, transplantation of collagen/UC-MSCs significantly promoted ovarian angiogenesis with the increased expression of CD31. In general, collagen/UC-MSCs transplantation probably is an effective therapeutic strategy of POF.

Transplantation of umbilical cord-derived mesenchymal stem cells on a collagen scaffold improves ovarian function in a premature ovarian failure model of mice.

Disruptions of angiogenesis can have a significant effect on the healing of uterine scars. Human endometrial perivascular cells (CD146+PDGFRβ+) function as stem cells in the endometrium. Cysteine-rich angiogenic inducer 61 (CYR61) plays an important role in vascular development. The purpose of this study was to observe the effects of the transplantation of human endometrial perivascular cells (En-PSCs) overexpressing CYR61 on structural and functional regeneration in rat models of partial full-thickness uterine excision.

Transplantation of human endometrial perivascular cells with elevated CYR61 expression induces angiogenesis and promotes repair of a full-thickness uterine injury in rat.

The establishment of endometrial receptivity is a prerequisite for successful pregnancy. Women with adenomyosis possess a lower chance of clinical pregnancy after assisted reproductive technology, which is partially due to impaired endometrial receptivity. The establishment of endometrial receptivity requires the participation of multiple processes, and proper endometrial epithelial cell (EEC) proliferation is indispensable. Monoamine oxidase A (MAOA) is a key molecule that regulates neurotransmitter metabolism in the nervous system. In the present study, we demonstrated a novel role for MAOA in the establishment of endometrial receptivity in women with adenomyosis and in an adenomyotic mouse model. Attenuated MAOA impairs endometrial receptivity by promoting inappropriate proliferation of EECs via the downregulation of FOXO1 during the window of implantation. These results revealed that MAOA plays a vital role in endometrial receptivity in female reproduction.

Attenuated monoamine oxidase a impairs endometrial receptivity in women with adenomyosis via downregulation of FOXO1†.

Oogenesis is a fundamental process of human reproduction, and mitochondria play crucial roles in oocyte competence. Mitochondrial ATP-dependent Lon protease 1 (LONP1) functions as a critical protein in maintaining mitochondrial and cellular homeostasis in somatic cells. However, the essential role of LONP1 in maintaining mammalian oogenesis is far from elucidated.

The mitochondrial protease LONP1 maintains oocyte development and survival by suppressing nuclear translocation of AIFM1 in mammals.

The purpose of this study was to explore the potential molecular mechanisms of excess homocysteine in relation to autophagic activity in the ovarian tissue of polycystic ovarian syndrome (PCOS) with hyperandrogenism.A PCOS model was constructed using ICR mice. ELISA was used to detect the Hcy levels in the serum and ovarian tissues of PCOS model. The expression level of key enzymes (Methionine synthase and Betaine-homocysteine methyltransferase, MTR and BHMT) in homocysteine metabolism and autophagy-related proteins were detected in ovarian tissues and mouse granulosa cells (mGCs) that were treated with homocysteine, androgen, autophagy inhibitors or BHMT-expressing plasmid by western blot and immunohistochemistry. Electron microscope experiments were used to evaluate autophagosomes in Hcy-treated mGCs. The prenatally androgenized (PNA) PCOS mouse model showed hyperhomocysteinemia and hyperandrogenism. Homocysteine levels displayed a significant increase, while its metabolic enzymes levels were significantly decreased in ovarian tissues of PCOS mice and dihydrotestosterone (DHT)-stimulated mGCs. The LC3II and Beclin1 expression levels were increased and the P62 and p-mTOR levels were decreased in vivo in ovarian tissue from the PCOS mice. The in vitro data were similarly with the in vivo by stimulation of mGCs with DHT or homocysteine. These effects could be diminished by the autophagy inhibitor (MHY1485), androgen receptor antagonists (ARN509) or BHMT-expressing plasmid. Androgen increases homocysteine concentration by downregulating the key enzymes in homocysteine metabolism. And then Hcy promotes GCs autophagy via the mTOR signal pathway.

Increased homocysteine regulated by androgen activates autophagy by suppressing the mammalian target of rapamycin pathway in the granulosa cells of polycystic ovary syndrome mice.

Poor decidualization and abnormal autophagy conditions in the endometria of adenomyosis patients have been reported previously. However, the specific regulatory mechanism of decidualization in adenomyosis and its relationship with autophagy levels have not been clarified.

Decreased Krüppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells.

Oxidative stress leads to ovarian functional decline by inducing granulosa cell (GC) apoptosis. Circular RNA circFoxo3 acts as a critical factor in regulating cell cycle and apoptosis, and cellular senescence in tumor cells. However, function of circFoxo3 is little understood in oxidative stress-induced injury of follicular GCs. In this study, we aimed to illustrate the regulation pattern of circFoxo3 in GCs under oxidative stress. CircFoxo3 was confirmed to be expressed in both human and mouse GCs by amplification with divergent primers and sequencing.  and  ovarian oxidative stress model, the expression of circFoxo3, FOXO3 protein, and its downstream targets were examined by quantitative real-time PCR and Western blotting, respectively. Knockdown of circFoxo3 was performed to evaluate the effects of circFoxo3-mediated GC apoptosis . RNA pull-down was used to discover the protein that interacted with circFoxo3 so as to illustrate the mechanism of circFoxo3 in GCs. Our results demonstrated that circFoxo3 was significantly upregulated in hydrogen peroxide (HO)-treated GCs and a 3-nitropropionic acid (3-NP)-induced mouse model of ovarian oxidative stress. Protein level of transcriptional factor FOXO3 was also remarkably increased in both  and  oxidative stress model, but  mRNA expression revealed no significant difference. Knockdown of endogenous circFoxo3 downregulated FOXO3 protein level and blocked HO-induced cell apoptosis. CircFoxo3 could pull down high levels of MDM2 protein that induced FOXO3 ubiquitination and degradation. Furthermore, knockdown of MDM2 and circFoxo3 showed remarkably higher level of apoptosis when compared with the knockdown of circFoxo3 alone. Our study suggested that circFoxo3 regulated FOXO3 protein level in GCs by reducing interactions between FOXO3 and MDM2. In conclusion, circFoxo3 was positively associated with FOXO3 protein and jointly played crucial roles in mediating GC apoptosis induced by oxidative stress.

ArticleTotal : 3	Year
Publication title Cited by 7	2022
Publication title Cited by 5	2023
Publication title Cited by 6	2022

Article	Year
Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility. Science China. Life sciences\| PubMed ID: 29546669	2018
Mitochondrial transfer from aged adipose-derived stem cells does not improve the quality of aged oocytes in C57BL/6 mice. Molecular reproduction and development\| PubMed ID: 30779242	2019
Transplantation of umbilical cord-derived mesenchymal stem cells on a collagen scaffold improves ovarian function in a premature ovarian failure model of mice. In vitro cellular & developmental biology. Animal\| PubMed ID: 30820812	2019
Transplantation of human endometrial perivascular cells with elevated CYR61 expression induces angiogenesis and promotes repair of a full-thickness uterine injury in rat. Stem cell research & therapy\| PubMed ID: 31215503	2019
Attenuated monoamine oxidase a impairs endometrial receptivity in women with adenomyosis via downregulation of FOXO1†. Biology of reproduction\| PubMed ID: 34568943	2021
The mitochondrial protease LONP1 maintains oocyte development and survival by suppressing nuclear translocation of AIFM1 in mammals. EBioMedicine\| PubMed ID: 34974310	2022
Increased homocysteine regulated by androgen activates autophagy by suppressing the mammalian target of rapamycin pathway in the granulosa cells of polycystic ovary syndrome mice. Bioengineered\| PubMed ID: 35485387	2022
Decreased Krüppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells. BMC molecular and cell biology\| PubMed ID: 35761172	2022
Circular RNA circFoxo3 Promotes Granulosa Cell Apoptosis Under Oxidative Stress Through Regulation of FOXO3 Protein. DNA and cell biology\| PubMed ID: 36394459	2022

Xiaoqiang Sheng

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