Article
Environmental Sciences
Hai'e Xu, Wanshuang Cao, Hongliang Sun, Shougang Zhang, Pan Li, Surong Jiang, Caiyun Zhong
Summary: Studies have shown that DEHP induced significant hormetic effects at environmentally relevant concentrations (12 and 36 μg/L), leading to U-shaped or inverted U-shaped responses in gene expression levels related to stress response (CAT, GST, and MgGLYZ) and antioxidant enzyme activities (SOD and CAT). The metabolic profiles revealed that DEHP generally caused monophasic response in osmotic regulation (homarine) and biphasic response (hormesis) in energy metabolism (glucose, glycogen, and amino acids). These findings can assist in ecological risk assessment of DEHP and determination of hormetic dose responses.
FRONTIERS IN MARINE SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Liselott Kallsten, Radwa Almamoun, Paula Pierozan, Erik Nylander, Kalliroi Sdougkou, Jonathan W. Martin, Oskar Karlsson
Summary: This study found that di-n-butyl phthalate (DBP) exposure can lead to persistent effects on testosterone synthesis and spermatogenesis in adult male mice, resulting in decreased testosterone levels. The study also revealed increased levels of key cells and proteins, including steroidogenic enzymes, oxidative stress markers, and germ cell markers, in response to DBP exposure.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Fan Zhang, Hualong Zhen, Hengshun Cheng, Fengying Hu, Yunfei Jia, Binbin Huang, Minmin Jiang
Summary: This study found that gestational exposure to DEHP caused liver dysfunction and hepatocyte morphology changes in pregnant mice. It also increased oxidative stress, iron accumulation, and levels of ferroptosis-related indicators, while decreasing the expression of related genes. The ferroptosis inhibitor Fer-1 attenuated DEHP-induced liver injury and ferroptosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Benjamin M. Dungar, Chad D. Schupbach, Jessie R. Jacobson, Phillip G. Kopf
Summary: The study found that BDE-47 significantly increased aldosterone and cortisol secretion in HAC15 cells, as well as gene expression related to corticosteroid synthesis and mitochondrial metabolism. In Sprague Dawley rats, adrenal weight was significantly increased in BDE-47 treatment groups, with a notable rise in plasma corticosterone levels in the 100 μg BDE-47/kg treatment group. These results indicate that BDE-47 disrupts corticosteroid secretion and supports the notion that PBDEs could act as endocrine disruptors.
Article
Endocrinology & Metabolism
Benjamin M. Dungar, Chad D. Schupbach, Jessie R. Jacobson, Phillip G. Kopf
Summary: The study found that BDE-47 significantly increases adrenal corticosteroid secretion and upregulates gene expression of enzymes involved in corticosteroid synthesis and mitochondrial metabolism. In the rat experiment, adrenal weight and plasma corticosterone levels were significantly increased in the BDE-47 treatment groups, suggesting a potential disruption in corticosteroid regulation and supporting the role of PBDEs as endocrine disruptors.
Article
Microbiology
Sean Ting-Shyang Wei, Yi-Lung Chen, Yu-Wei Wu, Tien-Yu Wu, Yi-Li Lai, Po-Hsiang Wang, Wael Ismail, Tzong-Huei Lee, Yin-Ru Chiang
Summary: DEHP, the most widely used plasticizer globally, accumulates in estuarine sediments and poses adverse effects on ecosystems and human health. Through integrated meta-omics approaches, it was found that DEHP biodegradation in estuarine sediments mainly depends on synergistic networks between denitrifying proteobacteria. The side chain hydrolysis of DEHP is identified as the rate-limiting step in its degradation process.
Article
Biotechnology & Applied Microbiology
Yen-Shun Hsu, Yung-Hsin Liu, Chu-Hsuan Lin, Chih-Hsuan Tsai, Whei-Fen Wu
Summary: Burkholderia sp. SP4, isolated from agricultural soils, exhibits a high degradation capability of di-2-ethylhexyl-phthalate (DEHP). It can degrade up to 99% of DEHP (300 mg l(-1)) within 48 h in minimal salt (MS) media without additional carbon source. The optimal conditions for DEHP degradation by SP4 are determined to be at 35°C and pH 6.0. Supplementation of certain compounds in the media enhances the degradation activity. Kinetic analyses reveal that SP4 degrades DEHP through a first-order reaction and has a better degradative activity compared to other known microbes. Metabolic intermediates of DEHP are identified for SP4, indicating a novel degradation pathway diverged from benzoate products. This study provides insight into a resilient DEHP-degradable bacterium and a new pathway for DEHP biodegradation, which can be applied in the removal of DEHP from various environments.
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
(2023)
Article
Environmental Sciences
Pengfei Hou, Wenting Dai, Yanshan Jin, Fengqi Zhao, Jianxin Liu, Hongyun Liu
Summary: This study demonstrates that DEHP exposure has adverse effects on lactation, including energy insufficiency, inflammation activation, oxidative stress aggravation, and disturbance of milk production. These findings are important for understanding the health risks of the plastic additive DEHP on female lactation dysfunction.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Environmental Sciences
Delnia Ahmadpour, Sakina Mhaouty-Kodja, Valerie Grange-Messent
Summary: Exposure to low doses of DEHP or an environmental phthalate mixture was found to increase BBB permeability, affect glial activation and neuroinflammation in specific brain regions. This suggests that exposure to endocrine disruptors like phthalates may pose a risk to cerebrovascular function.
Article
Environmental Sciences
M. K. Dziobak, R. S. Wells, E. C. Pisarski, E. F. Wirth, L. B. Hart
Summary: This study evaluated exposure to phthalate metabolites in free-ranging bottlenose dolphins, finding that approximately 75% of the dolphins had detectable concentrations of at least one phthalate metabolite. Sex and age did not significantly affect the detection and concentration of phthalate metabolites.
Article
Environmental Sciences
Suzanne Ducroq, Eric Duplus, Lucille Penalva-Mousset, Francesca Trivelloni, Aurore L'honore, Caroline Chabat-Courrede, Ivan Nemazanyy, Valerie Grange-Messent, Isabelle Petropoulos, Sakina Mhaouty-Kodja
Summary: We studied the cellular mechanisms induced by chronic exposure of adult male mice to low doses of di(2-ethylhexyl) phthalate (DEHP) alone or in an environmental phthalate mixture. The results showed differences in behavior, neural structure, and metabolism between mice exposed to DEHP alone or in a phthalate mixture. These differences were associated with changes in dendritic spine density, protein levels of glutamate receptors, and components of the kynurenine pathway of tryptophan metabolism.
ENVIRONMENTAL HEALTH PERSPECTIVES
(2023)
Article
Environmental Sciences
Ying Zhang, Jingjing Li, Wei Shi, Lu Lu, Qian Zhou, Hu Zhang, Ran Liu, Yuepu Pu, Lihong Yin
Summary: With the increased production and use of plastic products, global plastic pollution has become a serious issue. The plasticizer DEHP, commonly used in plastic production, raises concerns for human health, particularly regarding damage to the reproductive system. The role of DEHP in promoting reproductive aging and its underlying mechanisms are still not well-studied, making it significant to explore. In this study, Caenorhabditis elegans (C. elegans) was used as a model organism to investigate the mechanisms of DEHP-induced female reproductive senescence. The results showed that DEHP reduced offspring numbers and gonad area, leading to shortened reproductive and lifespan, as well as abnormal somatic gonad structures, oxidative stress, and autophagy. Additionally, the effects of DEHP were shown to be passed down to offspring not directly exposed to DEHP.
ENVIRONMENTAL POLLUTION
(2023)
Article
Environmental Sciences
XueXia Liu, YaNan Liu, Zi Teng, YuSheng Zhang, ZeLin Wang, Peng Zhu, MeiNa Xie, FuJun Liu
Summary: This study found that DEHP exposure reduces testis weight, serum testosterone levels, and sperm quality and function in male mice. DEHP exposure leads to decreased sperm count, motility, acrosome reaction rate, sperm-egg binding capacity, and blastocyte formation. DEHP also affects antioxidant indicators, protein expressions, cell proliferation, and apoptosis pathways in the testis.
Article
Biochemistry & Molecular Biology
Yoshifumi Horie, Miho Nomura, Babu Rajendran Ramaswamy, Hiroya Harino, Chee Kong Yap, Hideo Okamura
Summary: Water pollution caused by plasticizers is a severe environmental issue worldwide. This study investigated the effects of the nonphthalate bis(2-ethylhexyl) sebacate (DEHS) plasticizer on the gene expression levels of thyroid hormone-related, reproduction-related, and estrogen-responsive genes in Japanese medaka. The results showed that DEHS could disrupt the thyroid hormone-related gene expression and metabolism in fish, but did not have dose-dependent effects on the gene expression levels of other reproductive-related genes.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2023)
Article
Environmental Sciences
Delnia Ahmadpour, Sakina Mhaouty-Kodja, Valerie Grange-Messent
Summary: This study found that exposure of adult male mice to low doses of di(2-ethylhexyl)phthalate (DEHP) can lead to loss of blood-brain barrier (BBB) integrity and damage in the medial preoptic area (mPOA) involved in male sexual behavior. The exposure to DEHP resulted in reduced androgen receptor (AR) levels and decreased components of the basement membrane and cell-matrix interaction, leading to neurodegeneration. The findings suggest that environmental exposure to endocrine disruptors like phthalates can disrupt glio-neurovascular coupling and alter sexual behavior.
ENVIRONMENTAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Jinjiang Fan, Vassilios Papadopoulos
Summary: Deletion of the TSPO gene in MA-10 cells results in reduced mitochondrial membrane potential and significant changes in nuclear gene expression. This is likely due to dysregulation of several signaling pathways, including those involved in regulating membrane potential, calcium signaling, extracellular matrix, and phagocytosis. The compensatory response to loss of TSPO involves changes in expression of transcription factors, such as key members of the NF-kappa B pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Jinjiang Fan, Daniel B. Martinez-Arguelles, Vassilios Papadopoulos
Summary: SINE B2 possesses two promoters for producing short B2-S RNAs and long non-coding RNA (B2-AS lncRNAs). The study on B2-AS transcript sequence revealed that B2-AS lncRNAs regulate the expression of target genes through a locus-specific effect.
Article
Biochemistry & Molecular Biology
Melanie Galano, Yuchang Li, Lu Li, Chantal Sottas, Vassilios Papadopoulos
Summary: Leydig cells contain STAR which plays a role in transporting cholesterol into mitochondria for steroidogenesis, while the function of constitutive STAR in Leydig cells is unclear. Studies have shown that constitutive STAR is involved in accumulating diacylglycerol (DAG) in lipid droplets in addition to cholesterol transport. This may impact cell functions mediated by DAG signaling.STAR KO cells fail to produce progesterone in response to certain hormones and TSPO ligands, but show increased cholesteryl ester, phosphatidylcholine, and diacylglycerol contents in their lipid droplets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sathvika Venugopal, Melanie Galano, Rachel Chan, Esha Sanyal, Leeyah Issop, Sunghoon Lee, Lorne Taylor, Pushwinder Kaur, Edward Daly, Vassilios Papadopoulos
Summary: The study demonstrated that cAMP stimulation during steroidogenesis leads to significant lipidome remodeling, with changes in lipid composition in different organelles. The findings suggest that lipid trafficking between organelles plays a crucial role in hormone-induced steroid production, indicating extensive organelle remodeling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Endocrinology & Metabolism
Yiqi Christina Lin, Vassilios Papadopoulos
Summary: Neurosteroids, synthesized locally in the nervous system, have important neuromodulatory and neuroprotective effects. Research suggests differences in steroidogenesis between the nervous system and the periphery, particularly in the presence of the enzyme CYP11A1. Further understanding of neurosteroidogenesis is crucial for future neurosteroid-based therapies.
FRONTIERS IN NEUROENDOCRINOLOGY
(2021)
Review
Urology & Nephrology
Lu Li, Vassilios Papadopoulos
Summary: In Leydig cell dysfunction, treatment with testosterone replacement therapy (TRT) can lead to adverse effects such as infertility. Stem-cell-based therapy shows promise in re-establishing testosterone-producing cell lineages for transplantation therapy.
NATURE REVIEWS UROLOGY
(2021)
Article
Endocrinology & Metabolism
Melanie Galano, Vassilios Papadopoulos
Summary: The steroidogenic acute regulatory protein (STAR) is critical for cholesterol transport into the mitochondria and plays a role in its processing. This study found that deficiency or overexpression of STAR can lead to mitochondrial dysfunction, suggesting the importance of constitutive STAR for proper mitochondrial structure and function.
Review
Biochemistry & Molecular Biology
Melanie Galano, Sathvika Venugopal, Vassilios Papadopoulos
Summary: This review discusses the importance of cholesterol transport proteins and their roles in the trafficking and metabolism of cholesterol and other lipids in cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Andrology
Samuel Garza, Vassilios Papadopoulos
Summary: Reduced serum testosterone has negative effects on men's health and quality of life, and finding alternative treatments to testosterone replacement therapy is desirable. Research on testosterone formation in Leydig cells has identified potential targets for increasing endogenous testosterone biosynthesis. Enhancing steroidogenesis in Leydig cells could be an effective therapeutic approach, however, the development of ligands for steroidogenic proteins may have off-target effects. First-in-class biologics and transplantation of induced human Leydig-like cells offer promising strategies for enhancing endogenous steroid formation in hormone deficient patients.
Article
Biochemistry & Molecular Biology
Samuel Garza, Liting Chen, Melanie Galano, Garett Cheung, Chantal Sottas, Lu Li, Yuchang Li, Barry R. Zirkin, Vassilios Papadopoulos
Summary: This study found that the decline of mitochondrial translocator protein (TSPO) may result in disruptions in mitochondrial function and morphology, and is associated with declining Leydig cell (LC) function and reduced testosterone levels in the blood. Restoring mitochondrial function and promoting steroid formation can be achieved by enhancing mitochondrial fusion. These findings suggest that maintaining or enhancing mitochondrial fusion may be a therapeutic strategy for maintaining testosterone levels during aging.
Article
Cell Biology
Lu Li, Chantal M. Sottas, Hsu-Yu Chen, Yuchang Li, Haoyi Cui, Jason S. Villano, Joseph L. Mankowski, Paula M. Cannon, Vassilios Papadopoulos
Summary: Our study shows that SARS-CoV-2 can enter human Leydig-like cells (hLLCs) through a distinct pathway and alter testosterone production. This finding is significant for understanding the impact of the SARS-CoV-2 virus on the human body and the mechanisms of disease transmission.
Review
Biochemistry & Molecular Biology
Liting Chen, Yuchang Li, Alexander Zambidis, Vassilios Papadopoulos
Summary: Mitochondrial membrane protein ATAD3A is crucial for the maintenance of mitochondrial DNA, structure, and function. Mutations in ATAD3A have been found to disrupt mitochondrial structure, function, and dynamics, leading to severe neurological symptoms and early mortality. This review highlights the importance of ATAD3A in mitochondrial dynamics and its interaction with other mitochondrial/ER proteins. It also discusses the impact of ATAD3A mutations on various mitochondrial functions, including autophagy, mitophagy, mitochondrial morphology, and respiratory chain activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Melanie Galano, Shereen Ezzat, Vassilios Papadopoulos
Summary: This study reports the first patient with a heterozygous SCP2 mutation leading to SCPx deficiency. The patient exhibited clinical symptoms including progressive brainstem neurodegeneration, cardiac dysrhythmia, muscle wasting, and azoospermia. Analysis of fatty acids, protein expression, and metabolic pathways suggested the association of SCPx deficiency with various metabolic processes. Treatment interventions increasing SCPx levels may have therapeutic potential for reversing the effects of SCPx deficiency.
Article
Pharmacology & Pharmacy
Vassilios Papadopoulos, Dana Goldman, Clay Wang, Michele Keller, Steven Chen
Summary: Top challenges facing the future of pharmacy include limited clinical practice opportunities, oversupply of pharmacists, and high drug costs. Major technological disrupters include changes in the drug distribution system, automation/robotics, and new therapeutic approaches.
