Diabetes is a chronic metabolic disorder characterized by hyperglycemia and associated with many health complications due to the long-term damage and dysfunction of various organs. A consequential complication of diabetes in men is reproductive dysfunction, reduced fertility, and poor reproductive outcomes. However, the molecular mechanisms responsible for diabetic environment-induced sperm damage and overall decreased reproductive outcomes are not fully established. We evaluated the effects of type 2 diabetes exposure on the reproductive system and the reproductive outcomes of males and their male offspring, using a mouse model. We demonstrate that paternal exposure to type 2 diabetes mediates intergenerational and transgenerational effects on the reproductive health of the offspring, especially on sperm quality, and on metabolic characteristics. Given the transgenerational impairment of reproductive and metabolic parameters through two generations, these changes likely take the form of inherited epigenetic marks through the germline. Our results emphasize the importance of improving metabolic health not only in women of reproductive age, but also in potential fathers, in order to reduce the negative impacts of diabetes on subsequent generations.
- MeSH
- diabetes mellitus 2. typu krev chemicky indukované genetika MeSH
- dieta s vysokým obsahem tuků škodlivé účinky MeSH
- experimentální diabetes mellitus MeSH
- fenotyp * MeSH
- infertilita krev chemicky indukované genetika MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- paternální dědičnost účinky léků genetika MeSH
- spermie účinky léků fyziologie MeSH
- streptozocin toxicita MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The pathogenesis of Alzheimer's disease (AD), the most prevalent form of dementia, remains unclear. Over the past few years, evidence has accumulated indicating that perturbed cerebral bioenergetics and neuroinflammation may compromise cognitive functions and precedes the onset of AD and that impaired function of glial cells can likely contribute to the development of the disease. Recently, N6-methyladenosine (m6A) modification of RNA has been implicated in the regulation of different processes in the brain and to play a potential role in neurodegeneration. In the present study, we investigated the potential role of the m6A machinery enzymes in a streptozotocin (STZ) model of AD in human astrocytoma CCF-STTG1 cells. We observed that STZ-treated astrocytes expressed significantly higher levels of m6A demethylase fat mass and obesity-associated protein (FTO) and m6A reader YTHDF1 (YTH domain-containing family protein 1). Our experiments revealed that MO-I-500, a novel pharmacological inhibitor of FTO, can strongly reduce the adverse effects of STZ. Inhibition of FTO enhanced the survival of cells exposed to STZ and suppressed oxidative stress, apoptosis, elevated expression of glial fibrillary acidic protein, mitochondrial dysfunction, and bioenergetic disturbances induced by this compound. Overall, the results of this study indicate that perturbed m6A signaling may be contributing to AD pathogenesis, likely by compromising astrocyte bioenergetics.
- MeSH
- adenosin MeSH
- astrocyty * MeSH
- gen pro FTO * MeSH
- lidé MeSH
- mitochondrie MeSH
- streptozocin toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The aqueous extract of Cichorium intybus (CIE) leaves have shown the properties of protecting against pancreatic β-cell damage by streptozotocin (STZ), but the molecular mechanisms of its protection are not completely elucidated yet. Our current study focuses on elucidating the mechanisms of these preventive effects of CIE in MIN6 cells and an in-vivo model of Wistar rats. CIE offers protection against STZ in MIN6 cells by reducing the pro-oxidants and increasing the activity of the antioxidant enzymes. In vitro results also indicated that CIE inhibited cytotoxicity, reduced Reactive oxygen species (ROS), maintained glucose-stimulated insulin secretion and reduced NF-κB p65 translocation into the nucleus. The group administered with a 250 mg/kg dose of CIE in vivo has shown an ability to maintain blood glucose level and also to preserve the number and morphology of pancreatic islets when compared to the diabetic group treated with STZ. Probably, active compounds like quercetin, rutin, and catechin present in CIE, preserve the integrity of pancreatic islets thereby protecting β-cells from the adverse effects of STZ.
- MeSH
- čekanka obecná * chemie metabolismus účinky léků MeSH
- diabetes mellitus chemicky indukované MeSH
- krysa rodu rattus MeSH
- ochranné faktory MeSH
- streptozocin * farmakologie škodlivé účinky toxicita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- hodnotící studie MeSH
- MeSH
- antibakteriální látky toxicita MeSH
- diabetes mellitus chemicky indukované MeSH
- experimenty na zvířatech MeSH
- fixní kombinace léků MeSH
- hypoglykemie MeSH
- krysa rodu rattus MeSH
- Langerhansovy ostrůvky patologie sekrece účinky léků MeSH
- nádory slinivky břišní chemicky indukované MeSH
- niacinamid toxicita MeSH
- streptozocin toxicita MeSH
- Check Tag
- krysa rodu rattus MeSH
