scholarly journals Implications of environmental toxicants on ovarian follicles: how it can adversely affect the female fertility?

2021 ◽  
Author(s):  
Keerthi Priya ◽  
Manjunath Setty ◽  
Uddagiri Venkanna Babu ◽  
Karkala Sreedhara Ranganath Pai
Keyword(s):  
Polycystic Ovary ◽  
Endocrine Disrupting Chemicals ◽  
Epidemiological Studies ◽  
Female Fertility ◽  
Environmental Toxicants ◽  
Primordial Follicles ◽  
Reproductive Life ◽  
Sanitary Product

AbstractThe pool of primordial follicles formed in the ovaries during early development determines the span and quality of fertility in the reproductive life of a woman. As exposure to occupational and environmental toxicants (ETs) has become inevitable, consequences on female fertility need to be established. This review focuses on the ETs, especially well-studied prototypes of the classes endocrine disrupting chemicals (EDCs), heavy metals, agrochemicals, cigarette smoke, certain chemicals used in plastic, cosmetic and sanitary product industries etc that adversely affect the female fertility. Many in vitro, in vivo and epidemiological studies have indicated that these ETs have the potential to affect folliculogenesis and cause reduced fertility in women. Here, we emphasize on four main conditions: polycystic ovary syndrome, primary ovarian insufficiency, multioocytic follicles and meiotic defects including aneuploidies which can be precipitated by ETs. These are considered main causes for reduced female fertility by directly altering the follicular recruitment, development and oocytic meiosis. Although substantial experimental evidence is drawn with respect to the detrimental effects, it is clear that establishing the role of one ET as a risk factor in a single condition is difficult as multiple conditions have common risk factors. Therefore, it is important to consider this as a matter of public and wildlife health.

scholarly journals miR-378-3p maintains the size of mouse primordial follicle pool by regulating cell autophagy and apoptosis

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Xiaowen Sun ◽  
Francesca Gioia Klinger ◽  
Jing Liu ◽  
Massimo De Felici ◽  
Wei Shen ◽  
...  
Keyword(s):  
Post Partum ◽  
Expression System ◽  
Primordial Follicle ◽  
Underlying Mechanism ◽  
Newborn Mice ◽  
Primordial Follicles ◽  
Reproductive Life ◽  
Reproductive Life Span

Abstract Primordial follicle pool provides all available oocytes throughout the whole reproductive life span. Abnormal regulation in primordial follicle assembly leads to abnormal size of primordial follicle pool, even causes infertility. Here, miR-378-3p was proved to regulate mouse primordial follicle assembly both in vivo and in vitro. The expression of miR-378-3p significantly increased in mice ovaries from 17.5 dpc (days post coitum) up to 3 dpp (day post partum) compared with the expression of 16.5 dpc ovaries, which suggested that miR-378-3p was involved in primordial follicle assembly. To uncover the underlying mechanism, newborn mice ovaries were cultured in vitro in the presence of rapamycin and 3-methyladenine, which showed that the expression of miR-378-3p changed together with the percentage of primordial follicle. Moreover, during the normal process of primordial follicle assembly between 17.6 dpc and 3 dpp, autophagy is activated, while, apoptosis is inhibited. The in vivo results showed that newborn mice starved for 1.5 days showing the increased miR-378-3p, activated autophagy and inhibited apoptosis in the ovaries, had more percentage of primordial follicles. Over-expression of miR-378-3p using miR-378-3p agomir caused increased percentage of primordial follicle, increased level of autophagy, and decreased level of apoptosis. Knockdown of miR-378-3p by miR-378-3p antiagomir had the opposite results. Using pmirGLO Dual-Luciferase miRNA Target Expression system, we confirmed both PDK1 and Caspase9 were targets of miR-378-3p, which suggested that miR-378-3p activated autophagy by targeting PDK1 and inhibited apoptosis by targeting Caspase9. MiR-378-3p could be used as a biomarker of diseases caused by abnormal size of primordial follicle pool for diagnosis, prevention, or therapy.

scholarly journals In vitro ovarian culture system provides insight into the mechanism underlying follicle assembly in vivo

Development ◽  
2021 ◽  
pp. dev.197459
Author(s):  
Ren Tanimoto ◽  
Kiyono Sekii ◽  
Kanako Morohaku ◽  
Jianzhen Li ◽  
David Pepin ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Endocrine Disrupting Chemicals ◽  
Ectopic Expression ◽  
Perinatal Period ◽  
Primordial Follicles ◽  
Estrogen Exposure ◽  
Endocrine Disrupting ◽  
Insight Into

In mammals, primordial follicles assembled in fetuses or during infancy constitute the oocyte resources for life. Exposure to 17beta-estradiol and phytogenic or endocrine-disrupting chemicals during pregnancy and/or the perinatal period leads to the failure of normal follicle formation. However, the mechanisms underlying estrogen-mediated abnormal follicle formation and physiological follicle formation in the presence of endogenous natural estrogen are not well-understood. Here, we reveal that estrogen receptor 1, activated by estrogen, binds to the 5′ region of the anti-Mullerian hormone (Amh) gene and upregulates its transcription before follicle formation in cultured mouse fetal ovaries. Ectopic expression of AMH protein was observed in pregranulosa cells of these explants. Furthermore, AMH addition to the culture medium inhibited normal follicle formation. Conversely, alpha-fetoprotein (AFP) produced in fetal liver reportedly blocks estrogen action, although its role in follicle formation is unclear. We further demonstrated that AFP addition to the medium inhibited ectopic AMH expression via estrogen, leading to successful follicle formation in vitro. Collectively, our in vitro experiments suggest that upon estrogen exposure, the integrity of follicle assembly in vivo is ensured by AFP.

scholarly journals Epigenetic Transgenerational Inheritance of the Effects of Obesogen Exposure

2021 ◽  
Vol 12 ◽  
Author(s):  
Nicole Mohajer ◽  
Erika M. Joloya ◽  
Jeongbin Seo ◽  
Toshi Shioda ◽  
Bruce Blumberg
Keyword(s):  
Large Scale ◽  
Metabolic Disorders ◽  
Endocrine Disrupting Chemicals ◽  
Epidemiological Studies ◽  
Phenotypic Traits ◽  
Transgenerational Inheritance ◽  
Transgenerational Effects ◽  
Inherited Susceptibility

Obesity and metabolic disorders have become a worldwide pandemic affecting millions of people. Although obesity is a multifaceted disease, there is growing evidence supporting the obesogen hypothesis, which proposes that exposure to a subset of endocrine disrupting chemicals (EDCs), known as obesogens, promotes obesity. While these effects can be observed in vitro using cell models, in vivo and human epidemiological studies have strengthened this hypothesis. Evidence from animal models showed that the effects of obesogen exposure can be inherited transgenerationally through at least the F4 generation. Transgenerational effects of EDC exposure predispose future generations to undesirable phenotypic traits and diseases, including obesity and related metabolic disorders. The exact mechanisms through which phenotypic traits are passed from an exposed organism to their offspring, without altering the primary DNA sequence, remain largely unknown. Recent research has provided strong evidence suggesting that a variety of epigenetic mechanisms may underlie transgenerational inheritance. These include differential DNA methylation, histone methylation, histone retention, the expression and/or deposition of non-coding RNAs and large-scale alterations in chromatin structure and organization. This review highlights the most recent advances in the field of epigenetics with respect to the transgenerational effects of environmental obesogens. We highlight throughout the paper the strengths and weaknesses of the evidence for proposed mechanisms underlying transgenerational inheritance and why none of these is sufficient to fully explain the phenomenon. We propose that changes in higher order chromatin organization and structure may be a plausible explanation for how some disease predispositions are heritable through multiple generations, including those that were not exposed. A solid understanding of these possible mechanisms is essential to fully understanding how environmental exposures can lead to inherited susceptibility to diseases such as obesity.

scholarly journals Hypoxia induces the dormant state in oocytes through expression of Foxo3

2019 ◽  
Vol 116 (25) ◽  
pp. 12321-12326 ◽  
Author(s):  
So Shimamoto ◽  
Yohei Nishimura ◽  
Go Nagamatsu ◽  
Norio Hamada ◽  
Haruka Kita ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Analysis ◽  
Hypoxic Condition ◽  
Primordial Follicle ◽  
Primordial Follicles ◽  
Dormant State ◽  
Precise Understanding ◽  
Reproductive Life

In mammals, most immature oocytes remain dormant in the primordial follicles to ensure the longevity of female reproductive life. A precise understanding of mechanisms underlying the dormancy is important for reproductive biology and medicine. In this study, by comparing mouse oogenesis in vivo and in vitro, the latter of which bypasses the primordial follicle stage, we defined the gene-expression profile representing the dormant state of oocytes. Overexpression of constitutively active FOXO3 partially reproduced the dormant state in vitro. Based on further gene-expression analysis, we found that a hypoxic condition efficiently induced the dormant state in vitro. The effect of hypoxia was severely diminished by disruption of the Foxo3 gene and inhibition of hypoxia-inducible factors. Our findings provide insights into the importance of environmental conditions and their effectors for establishing the dormant state.

scholarly journals A predictive in vitro risk assessment platform for pro-arrhythmic toxicity using human 3D cardiac microtissues

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Celinda M. Kofron ◽  
Tae Yun Kim ◽  
Fabiola Munarin ◽  
Arvin H. Soepriatna ◽  
Rajeev J. Kant ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Action Potentials ◽  
Induced Pluripotent Stem Cell ◽  
Human Action ◽  
Environmental Toxicants ◽  
Pharmaceutical Drugs ◽  
Industrial Chemicals ◽  
Endocrine Disrupting Chemical

AbstractCardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia and sudden cardiac death accurately is critical for defining safety profiles. Currently available approaches have limitations including a focus on single select ion channels, the use of non-human species in vitro and in vivo, and limited direct physiological translation. We have advanced the robustness and reproducibility of in vitro platforms for assessing pro-arrhythmic cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts in 3-dimensional microtissues. Using automated algorithms and statistical analyses of eight comprehensive evaluation metrics of cardiac action potentials, we demonstrate that tissue-engineered human cardiac microtissues respond appropriately to physiological stimuli and effectively differentiate between high-risk and low-risk compounds exhibiting blockade of the hERG channel (E4031 and ranolazine, respectively). Further, we show that the environmental endocrine disrupting chemical bisphenol-A (BPA) causes acute and sensitive disruption of human action potentials in the nanomolar range. Thus, this novel human 3D in vitro pro-arrhythmic risk assessment platform addresses critical needs in cardiotoxicity testing for both environmental and pharmaceutical compounds and can be leveraged to establish safe human exposure levels.

scholarly journals Antidiabetic Properties of Naringenin: A Citrus Fruit Polyphenol

Biomolecules ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 99 ◽  
Author(s):  
Danja J. Den Hartogh ◽  
Evangelia Tsiani
Keyword(s):  
Insulin Resistance ◽  
Animal Studies ◽  
Citrus Fruit ◽  
Epidemiological Studies ◽  
Personal Health ◽  
Current Review ◽  
Vegetables And Fruits

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringenin.

In Vitro and In Vivo Developmental Ability of Oocytes Derived from Porcine Primordial Follicles Xenografted into Nude Mice

2006 ◽  
Vol 52 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Kazuhiro KIKUCHI ◽  
Hiroyuki KANEKO ◽  
Michiko NAKAI ◽  
Junko NOGUCHI ◽  
Manabu OZAWA ◽  
...  
Keyword(s):  
Nude Mice ◽  
Primordial Follicles

scholarly journals Attenuation of Carcinogenesis and the Mechanism Underlying by the Influence of Indole-3-carbinol and Its Metabolite 3,3′-Diindolylmethane: A Therapeutic Marvel

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
V. L. Maruthanila ◽  
J. Poornima ◽  
S. Mirunalini
Keyword(s):  
Epidemiological Studies ◽  
Cruciferous Vegetables ◽  
Brussels Sprouts ◽  
Anticancer Properties ◽  
Depth Study ◽  
Dimeric Product ◽  
Indole Glucosinolate

Rising evidence provides credible support towards the potential role of bioactive products derived from cruciferous vegetables such as broccoli, cauliflower, kale, cabbage, brussels sprouts, turnips, kohlrabi, bok choy, and radishes. Many epidemiological studies point out thatBrassicavegetable protects humans against cancer since they are rich sources of glucosinolates in addition to possessing a high content of flavonoids, vitamins, and mineral nutrients. Indole-3-carbinol (I3C) belongs to the class of compounds called indole glucosinolate, obtained from cruciferous vegetables, and is well-known for tits anticancer properties. In particular, I3C and its dimeric product, 3,3′-diindolylmethane (DIM), have been generally investigated for their value against a number of human cancersin vitroas well asin vivo. This paper reviews an in-depth study of the anticancer activity and the miscellaneous mechanisms underlying the anticarcinogenicity thereby broadening its therapeutic marvel.

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