scholarly journals Ovarian Stem Cell Nests in Reproduction and Ovarian Aging

2017 ◽  
Vol 43 (5) ◽  
pp. 1917-1925 ◽  
Author(s):  
Haifeng Ye ◽  
Tuochen Zheng ◽  
Wei Li ◽  
Xiaoyan Li ◽  
Xinxin Fu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Immune System ◽  
Ovarian Function ◽  
Circulatory System ◽  
Primordial Follicle ◽  
Cell Aging ◽  
Germline Stem Cell ◽  
Primordial Follicles ◽  
Ovarian Aging

The fixed primordial follicles pool theory, which monopolized reproductive medicine for more than one hundred years, has been broken by the discovery, successful isolation and establishment of ovarian stem cells. It has brought more hope than ever of increasing the size of primordial follicle pool, improving ovarian function and delaying ovarian consenescence. Traditional view holds that stem cell aging contributes to the senility of body and organs. However, in the process of ovarian aging, the main factor leading to the decline of the reproductive function is the aging and degradation of ovarian stem cell nests, rather than the senescence of ovarian germ cells themselves. Recent studies have found that the immune system and circulatory system are involved in the formation of ovarian germline stem cell niches, as well as regulating the proliferation and differentiation of ovarian germline stem cells through cellular and hormonal signals. Therefore, we can improve ovarian function and delay ovarian aging by improving the immune system and circulatory system, which will provide an updated program for the treatment of premature ovarian failure (POF) and infertility.

scholarly journals Effects of shikonin on the development of ovarian follicles and female germline stem cells

2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110294
Author(s):  
Shu-Xin Ma ◽  
Li-Bo Tang ◽  
Zhi-Hang Chen ◽  
Min-Li Wei ◽  
Zi-Juan Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ovarian Follicles ◽  
Germline Stem Cell ◽  
Stem Cell Markers ◽  
Germline Stem Cells ◽  
Primordial Follicles ◽  
Cell Markers ◽  
Female Germline ◽  
Ovarian Index

Objective To investigate the effects and potential mechanism of action of shikonin (SHK) on the development of ovarian follicles and female germline stem cells (FGSCs). Methods Female Kunming adult mice were administered SHK (0, 20 and 50 mg/kg) by oral gavage. Cultures of FGSCs were treated with SHK 32 μmol/l for 24 h. The ovarian index in mouse ovaries was calculated. Numbers of primordial, primary and atretic follicles were counted. Germline stem cell markers and apoptosis were examined. Levels of glutathione (GSH), superoxide dismutase (SOD) and reactive oxygen species (ROS) were measured. Results Both doses of SHK significantly decreased the ovarian index, the numbers of primordial follicles, primary follicles and antral follicles in mice. SHK significantly increased the numbers of atretic follicles and atretic corpora lutea. SHK promoted apoptosis in vivo and in vitro. SHK significantly decreased the levels of the germline stem cell markers. SHK significantly lowered GSH levels and the activity of SOD in the peripheral blood from mice, whereas SHK significantly elevated cellular ROS content in FGSCs. Conclusions These current results suggested that follicular development and FGSCs were suppressed by SHK through the induction of apoptosis and oxidative stress might be involved in this pathological process.

scholarly journals Aging germline stem cells in C. elegans

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 740-740
Author(s):  
E Jane Hubbard
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell System ◽  
Cell Aging ◽  
Germline Stem Cell ◽  
Germline Stem Cells ◽  
C Elegans ◽  
Cell Pool ◽  
Stem Cell System ◽  
Stem Cell Pool

Abstract Failure to maintain stem cells with age is associated with conditions such as tissue degeneration and increased susceptibility to tissue damage. We use the C. elegans germline stem cell system as a model to study stem cell aging. This system combines a well-established model for aging with an accessible stem cell system, providing a unique opportunity to understand how aging influences stem cell dynamics. The germline stem/progenitor pool in in C. elegans becomes depleted over time. At the cellular level, aging influences both the size of the stem cell pool and the proliferation rate of stem cells. The flux of differentiated cells also affects how aging impacts the pool. This depletion is partially alleviated in mutants with reduced insulin/IGF-like signaling via inhibition of the transcription factor DAF-16/FOXO. In this role, DAF-16 does not act in the germ line, and its anatomical requirements are different from its previously described roles in larval germline proliferation, dauer control, and lifespan regulation. We found that DAF-16/FOXO is required in certain somatic cells in the proximal part of the reproductive system to regulate the stem cell pool. We also find that the degree to which various age-defying perturbations affect lifespan does not correlate with their effect on germline stem cell maintenance. We are investigating additional aspects of aging germline stem cells using this system.

Stem Cell Transplantation Improves Ovarian Function through Paracrine Mechanisms

2020 ◽  
Vol 20 (5) ◽  
pp. 347-355
Author(s):  
Wenlin Jiao ◽  
Xin Mi ◽  
Yingying Qin ◽  
Shidou Zhao
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Molecular Mechanisms ◽  
Ovarian Function ◽  
Loss Of Function ◽  
Ovarian Insufficiency ◽  
Ovarian Aging ◽  
Age Related

The ovary serves as the source of oocytes for the maintenance of female fertility and is a major supplier of sex hormones for endocrine homeostasis. Various circumstances such as genetic defects, autoimmune disorders, natural aging and environmental toxins can damage the ovaries leading to diminished ovarian function, and there are currently no effective treatment regimens for such loss of function. Stem cells show promise for treating many refractory diseases, and stem cell transplantation has been shown to be effective and safe as a new therapeutic method for ovarian injuries and ovarian aging in both animal models and women with premature ovarian insufficiency. However, the specific mechanisms that underlie the observed positive outcomes of improving ovarian function are not well understood. Evidence is mounting that stem cell-derived conditioned medium, exosomes, and trophic growth factors can also inhibit ovarian damage and alleviate the age-related fertility decline in female mice, indicating that stem cells exert the paracrine effects. Further studies to elucidate the cellular and molecular mechanisms, including signaling pathways, for improving ovarian function and promoting the secretory capacity of stem cells will fill the bench-to-bedside gap of stem cell therapy in the clinic. Furthermore, in-depth analyses of the stem cell secretome and identification of the key effective components will underlie a new paradigm in cell-free therapeutic strategies for ovarian insufficiency and ovarian aging.

scholarly journals Antioxidant Effects of Caffeic Acid Lead to Protection of Drosophila Intestinal Stem Cell Aging

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiao Sheng ◽  
Yuedan Zhu ◽  
Juanyu Zhou ◽  
La Yan ◽  
Gang Du ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Caffeic Acid ◽  
Stress Responses ◽  
Adult Stem Cells ◽  
Cell Function ◽  
Cell Aging ◽  
Positive Effects ◽  
Age Related ◽  
Tissue Aging

The dysfunction or exhaustion of adult stem cells during aging is closely linked to tissue aging and age-related diseases. Circumventing this aging-related exhaustion of adult stem cells could significantly alleviate the functional decline of organs. Therefore, identifying small molecular compounds that could prevent the age-related decline of stem cell function is a primary goal in anti-aging research. Caffeic acid (CA), a phenolic compound synthesized in plants, offers substantial health benefits for multiple age-related diseases and aging. However, the effects of CA on adult stem cells remain largely unknown. Using the Drosophila midgut as a model, this study showed that oral administration with CA significantly delayed age-associated Drosophila gut dysplasia caused by the dysregulation of intestinal stem cells (ISCs) upon aging. Moreover, administering CA retarded the decline of intestinal functions in aged Drosophila and prevented hyperproliferation of age-associated ISC by suppressing oxidative stress-associated JNK signaling. On the other hand, CA supplementation significantly ameliorated the gut hyperplasia defect and reduced environmentally induced mortality, revealing the positive effects of CA on tolerance to stress responses. Taken together, our findings report a crucial role of CA in delaying age-related changes in ISCs of Drosophila.

Serine Metabolism Controls Dental Pulp Stem Cell Aging by Regulating the DNA Methylation of p16

2020 ◽  
Vol 100 (1) ◽  
pp. 90-97
Author(s):  
R.L. Yang ◽  
H.M. Huang ◽  
C.S. Han ◽  
S.J. Cui ◽  
Y.K. Zhou ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Stem Cell ◽  
Dental Pulp ◽  
Permanent Teeth ◽  
Deciduous Teeth ◽  
Cell Aging ◽  
Differentiation Capacity ◽  
Stem Cell Aging ◽  
Serine Metabolism

To investigate the characteristics and molecular events of dental pulp stem cells (DPSCs) for tissue regeneration with aging, we isolated and analyzed the stem cells from human exfoliated deciduous teeth (SHED) and permanent teeth of young (Y-DPSCs) and old (A-DPSCs) adults. Results showed that the stemness and osteogenic differentiation capacity of DPSCs decreased with aging. The RNA sequencing results showed that glycine, serine, and threonine metabolism was one of the most enriched gene clusters among SHED, Y-DPSCs, and A-DPSCs, according to analysis based on the Kyoto Encyclopedia of Genes and Genomes. The expression of serine metabolism–related enzymes phosphoserine aminotransferase 1 (PSAT1) and phosphoglycerate (PHGDH) decreased in A-DPSCs and provided less methyl donor S-adenosylmethionine (SAM) for DNA methylation, leading to the hypomethylation of the senescence marker p16 (CDNK2A). Furthermore, the proliferation and differentiation capacity of Y-DPSCs and SHED decreased after PHGDH siRNA treatment, which reduced the level of SAM. Convincingly, the ratios of PSAT1-, PHGDH-, or proliferating cell nuclear antigen–positive cells in the dental pulp of old permanent teeth were less than those in the dental pulp of deciduous teeth and young permanent teeth. In summary, the stemness and differentiation capacity of DPSCs decreased with aging. The decreased serine metabolism in A-DPSCs upregulated the expression of p16 via attenuating its DNA methylation, resulting in DPSC aging. Our finding indicated that serine metabolism and 1 carbon unit participated in stem cell aging, which provided new direction for stem cell aging study and intervention.

scholarly journals Loss of foxo rescues stem cell aging in Drosophila germ line

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Filippo Artoni ◽  
Rebecca E Kreipke ◽  
Ondina Palmeira ◽  
Connor Dixon ◽  
Zachary Goldberg ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Stem Cell ◽  
Ionizing Radiation ◽  
Cell Injury ◽  
Germ Line ◽  
Adult Stem Cell ◽  
Cell Aging ◽  
Germline Stem Cells ◽  
Cell Cycle Reentry

Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of Drosophila melanogaster germline stem cells (GSCs) to survive exposure to low doses of ionizing radiation (IR) as a model of adult stem cell injury and identified a regeneration defect in aging GSCs: while aging GSCs survive exposure to IR, they fail to reenter the cell cycle and regenerate the germline in a timely manner. Mechanistically, we identify foxo and mTOR homologue, Tor as important regulators of GSC quiescence following exposure to ionizing radiation. foxo is required for entry in quiescence, while Tor is essential for cell cycle reentry. Importantly, we further show that the lack of regeneration in aging germ line stem cells after IR can be rescued by loss of foxo.

scholarly journals Follistatin Regulates Germ Cell Nest Breakdown and Primordial Follicle Formation

Endocrinology ◽  
2010 ◽  
Vol 152 (2) ◽  
pp. 697-706 ◽  
Author(s):  
Fuminori Kimura ◽  
Lara M. Bonomi ◽  
Alan L. Schneyer
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Ovarian Function ◽  
Primordial Follicle ◽  
Biochemical Properties ◽  
The Body ◽  
Protein Isoforms ◽  
Primordial Follicles ◽  
Reduced Rate ◽  
Regulatory Functions

Abstract Follistatin (FST) is an antagonist of activin and related TGFβ superfamily members that has important reproductive actions as well as critical regulatory functions in other tissues and systems. FST is produced as three protein isoforms that differ in their biochemical properties and in their localization within the body. We created FST288-only mice that only express the short FST288 isoform and previously reported that females are subfertile, but have an excess of primordial follicles on postnatal day (PND) 8.5 that undergo accelerated demise in adults. We have now examined germ cell nest breakdown and primordial follicle formation in the critical PND 0.5–8.5 period to test the hypothesis that the excess primordial follicles derive from increased proliferation and decreased apoptosis during germ cell nest breakdown. Using double immunofluorescence microscopy we found that there is virtually no germ cell proliferation after birth in wild-type or FST288-only females. However, the entire process of germ cell nest breakdown was extended in time (through at least PND 8.5) and apoptosis was significantly reduced in FST288-only females. In addition, FST288-only females are born with more germ cells within the nests. Thus, the excess primordial follicles in FST288-only mice derive from a greater number of germ cells at birth as well as a reduced rate of apoptosis during nest breakdown. These results also demonstrate that FST is critical for normal regulation of germ cell nest breakdown and that loss of the FST303 and/or FST315 isoforms leads to excess primordial follicles with accelerated demise, resulting in premature cessation of ovarian function.

Caloric restriction maintains stem cells through niche and regulates stem cell aging

2019 ◽  
Vol 98 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Nagarajan Maharajan ◽  
Karthikeyan Vijayakumar ◽  
Chul Ho Jang ◽  
Goang-Won Cho
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Caloric Restriction ◽  
Cell Aging ◽  
Stem Cell Aging

scholarly journals Age-Related Changes in Methylome and Transcriptome of Hematopotietic Stem Cells Underlie Natural Genetic Variations

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2660-2660
Author(s):  
Ying Liang
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Stem Cell ◽  
Aging Process ◽  
Expression Patterns ◽  
Genetic Variations ◽  
Cell Aging ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Age Related Changes

The aging of hematopoietic stem cells (HSCs) contributes to the aging of blood system and perhaps the whole organism. The aging process is coordinately determined by both genetic and epigenetic factors, and demonstrates inter-individual variations. We used high-throughput sequencing methods to study the age-dependent changes of genome-wide DNA methylation and gene expression patterns in HSCs of C57BL/6 (B6) and DBA/2 mouse strains, which have shown natural variations in HSC aging process. We observed global age-associated decrease of DNA methylation in both strains, but D2 HSCs have a stronger loss of epigenetic control than B6 stem cells during aging. Majority age-related changes of DNA methylation occur from young to mid-aged stages. We identified stable strain-specific differentially methylated regions (DMRs) that overlap with cis-eQTLs. Moreover, transcription factor binding site motifs are more likely to be disrupted in the DMRs, suggesting the potential impact of genetic variations on epigenetic regulation of HSC aging. We further demonstrated that strain-specific DMRs have more profound effects on the aging of B6 HSCs than D2 stem cells. Transposons are differentially regulated by the DMRs in the two strains, in which D2 HSCs are prone to transposon insertion. This study comprehensively investigated the effects of natural genetic and epigenetic variations on HSC aging. Loss of DNA methylation is an epigenetic signature of stem cell aging, and DNA methylation variations correlates with genetic variations, both contributing to inter-individual differences in stem cell and perhaps organismal aging. Disclosures No relevant conflicts of interest to declare.

scholarly journals Investigation of Stem Cell Aging Throughout the Lifetime and Therapeutic Opportunities

2020 ◽  
Author(s):  
Sarah Karimi ◽  
Setareh Raoufi ◽  
Zohreh Bagher
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Aging Process ◽  
Cell Function ◽  
Cell Activity ◽  
The Body ◽  
Natural Phenomenon ◽  
Cell Aging ◽  
Molecular Pathways ◽  
Stem Cell Aging

Introduction: Aging is a natural phenomenon that is caused by changes in the cells of the body. Theoretically, aging starts from birth and lasts throughout life. These changes affect the function of the cells. Also, in old tissues, the capacity for homeostasis and tissue repair is decline due to destructive changes in specific tissue stem cells, niche of stem cells and systemic factors that regulate stem cell activity. Understanding molecular pathways that disrupt stem cell function during aging is crucial for the development of new treatments for aging-associated diseases. In this article, the symptoms of stem cell aging and the key molecular pathways that are commonly used for the aging of stem cells were discussed. We will consider experimental evidence for all of the mechanisms and evaluate the way that can slow down or even stop the aging process. Finally, we will look at the aging process of three types of stem cells.

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