Functional Oocytes Derived from Granulosa Cells

Tian, Chenglei; Liu, Linlin; Ye, Xiaoying; Fu, Haifeng; Sheng, Xiaoyan; Wang, Lingling; Wang, Huasong; Dai, Hongyue; Liu, Lin

doi:10.1016/j.celrep.2019.11.080

Cited by 42 publications

(37 citation statements)

References 70 publications

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“…PGC‐like cells (PGCLCs) have been successfully achieved from pluripotent stem cells, embryonic stem cells, or induced pluripotent stem cells (Hayashi et al, 2012; Hikabe et al, 2016), as well as from chemically induced pluripotent stem cells by pure chemical reprogramming of adult somatic granulosa cells (Tian et al, 2019). PGCLCs reaggregated with E12.5 female gonadal somatic cells are subjected to ovarian cyst transplantation to obtain functional mature eggs (Hayashi et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…PGCLCs reaggregated with E12.5 female gonadal somatic cells are subjected to ovarian cyst transplantation to obtain functional mature eggs (Hayashi et al, 2012). Excitingly, PGCLCs derived from granulosa cells also can reconstitute ovarian functions in the recipient mice following kidney capsule transplantation (Tian et al, 2019). It is likely that PGCLCs derived from pluripotent stem cells or reprogrammed from somatic cells could be used to extend ovarian functions in combination with mTOR inhibition by INK128, opening wider applications in preservation of fertility and endocrine functions.…”

Section: Discussionmentioning

confidence: 99%

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Mtor inhibition by INK128 extends functions of the ovary reconstituted from germline stem cells in aging and premature aging mice

et al. 2021

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Stem cell transplantation has been generally considered as promising therapeutics in preserving or recovering functions of lost, damaged, or aging tissues. Transplantation of primordial germ cells (PGCs) or oogonia stem cells (OSCs) can reconstitute ovarian functions that yet sustain for only short period of time, limiting potential application of stem cells in preservation of fertility and endocrine function. Here, we show that mTOR inhibition by INK128 extends the follicular and endocrine functions of the reconstituted ovaries in aging and premature aging mice following transplantation of PGCs/OSCs. Follicular development and endocrine functions of the reconstituted ovaries by transplanting PGCs into kidney capsule of the recipient mice were maintained by INK128 treatment for more than 12 weeks, in contrast to the controls for only about 4 weeks without receiving the mTOR inhibitors. Comparatively, rapamycin also can prolong the ovarian functions but for limited time. Furthermore, our data reveal that INK128 promotes mitochondrial function in addition to its known function in suppression of immune response and inflammation. Taken together, germline stem cell transplantation in combination with mTOR inhibition by INK128 improves and extends the reconstituted ovarian and endocrine functions in reproductive aging and premature aging mice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mtor inhibition by INK128 extends functions of the ovary reconstituted from germline stem cells in aging and premature aging mice

et al. 2021

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“…GCs also support oocytes by producing nutrients and growth factors. GC death results in the abnormal development of oocytes [ 59 ]. The effect of miR-21 overexpression in BMSCs may be mediated by a reduction in the expression of programmed cell death protein 4 (PDCD4) and phosphatase and tensin homolog (PTEN).…”

Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

Esfandyari

Chugh

Park

et al. 2020

Cells

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Female infertility is a global medical condition that can be caused by various disorders of the reproductive system, including premature ovarian failure (POF), polycystic ovary syndrome (PCOS), endometriosis, Asherman syndrome, and preeclampsia. It affects the quality of life of both patients and couples. Mesenchymal stem cells (MSCs) have received increasing attention as a potential cell-based therapy, with several advantages over other cell sources, including greater abundance, fewer ethical considerations, and high capacity for self-renewal and differentiation. Clinical researchers have examined the therapeutic use of MSCs in female infertility. In this review, we discuss recent studies on the use of MSCs in various reproductive disorders that lead to infertility. We also describe the role of microRNAs (miRNAs) and exosomal miRNAs in controlling MSC gene expression and driving MSC therapeutic outcomes. The clinical application of MSCs holds great promise for the treatment of infertility or ovarian insufficiency, and to improve reproductive health for a significant number of women worldwide.

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“…In addition, StAR can transport the cholesterol from the outer to the inner mitochondrial membrane, where it is converted to pregnenolone by CYP11A1. Estradiol promotes the formation of follicles and gonadotropin receptors in the ovary [10,11], inhibits the apoptosis of GCs [12], facilitates the formation of corpus luteum, and maintains the corpus luteum and regulates steroid synthesis.…”

Section: Introductionmentioning

confidence: 99%

MiR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine granulosa cells

Shi

Zhou

et al. 2020

J Animal Sci Biotechnol

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Background Granulosa cells (GCs) proliferation and estradiol synthesis significantly affect follicular development. The miR-214-3p expression in the ovarian tissues of high-yielding sows is higher than that in low-yielding sows, indicating that miR-214-3p may be involved in sow fertility. However, the functions and mechanisms of miR-214-3p on GCs are unclear. This study focuses on miR-214-3p in terms of the effects on GCs proliferation and estradiol synthesis. Results Our findings revealed that miR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine GCs. MiR-214-3p can increase the percentage of S-phase cells, the number of EdU labeled positive cells, and cell viability. However, E2 concentration was reduced after miR-214-3p agomir treatment. We also found that miR-214-3p up-regulates the expression of cell cycle genes including cell cycle protein B (Cyclin B), cell cycle protein D (Cyclin D), cell cycle protein E (Cyclin E), and cyclin-dependent kinase 4 (CDK4) at the transcription and translation levels, but down-regulates the mRNA and protein levels of cytochrome P450 family 11 subfamily A member 1 (CYP11A1), cytochrome P450 family 19 subfamily A member 1 (CYP19A1), and steroidogenic acute regulatory protein (StAR) (i.e., the key enzymes in estradiol synthesis). On-line prediction, bioinformatics analysis, a luciferase reporter assay, RT-qPCR, and Western blot results showed that the target genes of miR-214-3p in proliferation and estradiol synthesis are Mfn2 and NR5A1, respectively. Conclusions Our findings suggest that miR-214-3p plays an important role in the functional regulation of porcine GCs and therefore may be a target gene for regulating follicular development.

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Functional Oocytes Derived from Granulosa Cells

Abstract: Highlights d Granulosa cells can be reprogrammed to form oocytes by chemical reprogramming d Rock inhibition and crotonic acid facilitate the chemical induction of gPSCs from GCs d PGCLCs derived from gPSCs exhibit longer telomeres and high genomic stability

Cited by 42 publications

References 70 publications

Mtor inhibition by INK128 extends functions of the ovary reconstituted from germline stem cells in aging and premature aging mice

Mtor inhibition by INK128 extends functions of the ovary reconstituted from germline stem cells in aging and premature aging mice

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

MiR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine granulosa cells

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