Role of oxidative stress in germ cell apoptosis induced by di(2-ethylhexyl)phthalate

Kasahara, Emiko; Sato, Eisuke F.; Miyoshi, Manabu; Konaka, Ryusei; Hiramoto, Keiichi; Sasaki, Junzo; Tokuda, Masaaki; Nakano, Yoshihisa; Inoue, Masayasu

doi:10.1042/bj20020254

Cited by 280 publications

(159 citation statements)

References 47 publications

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“…Sperm counts in healthy men around the world have fallen by about 50 per cent in the last 50 years in the Western world (Auger et al, 1995;Kasahara et al, 2002). This may be attributed to the insufficient spermatozoa (oligozoospermia) or the lack of spermatozoa (azoospermia) (Yazama et al, 2006).…”

Section: Infertility Oxidative Stress and Vitamin Cmentioning

confidence: 99%

“…The male factor is responsible for 25 % of these cases (Sharlip et al, 2002;Liu et al, 2006;Agarwal et al, 2008). One male infertility mechanism is the excess production of reactive oxygen species (ROS) in sperm (Sharma & Agarwal, 1996;Chen et al, 2001;Kasahara et al, 2002;Agarwal et al, 2008). This induces nuclear DNA fragmentation, lipid peroxidation and protein cross links and results in cell death (Alvarez et al, 1987;Steenken, 1989;Tramer et al, 1998;Liu et al, 2006).…”

Section: Infertility Oxidative Stress and Vitamin Cmentioning

confidence: 99%

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Vitamin C and oxidative stress in the seminiferous epithelium

et al. 2011

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In this article, we focus on the fundamental role of vitamin C transporters for the normal delivery of vitamin C to germ cells in the adluminal compartment of seminiferous tubules. We argue that the redox status within spermatozoa or in semen is partly responsible for the etiology of infertility. In this context, antioxidant defence plays a critical role in male fertility. Vitamin C, a micronutrient required for a wide variety of metabolic functions, has long been associated with male reproduction. Two systems for vitamin C transport have been described in mammals. Facilitative hexose transporters (GLUTs), with 14 known isoforms to date, GLUT1-GLUT14, transport the oxidized form of vitamin C (dehydroascorbic acid) into the cells. Sodium ascorbic acid co-transporters (SVCTs), SVCT1 and SVCT2 transport the reduced form of vitamin C (ascorbic acid). Sertoli cells control germ cell proliferation and differentiation through cell-cell communication and form the blood-testis barrier. Because the blood-testis barrier limits direct access of molecules from the plasma into the adluminal compartment of the seminiferous tubule, one important question is the method by which germ cells obtain vitamin C. Some interesting results have thrown light on this matter. Expression of SVCT2 and some isoforms of GLUT transporters in the testis have previously been described. Our group has demonstrated that Sertoli cells express functionally active vitamin C transporters. Kinetic characteristics were described for both transport systems (SVCT and GLUT systems). Sertoli cells are able to transport both forms of vitamin C. These fi ndings are extremely relevant, because Sertoli cells may control the amount of vitamin C in the adluminal compartment, as well as regulating the availability of this metabolite throughout spermatogenesis.

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Section: Infertility Oxidative Stress and Vitamin Cmentioning

confidence: 99%

Section: Infertility Oxidative Stress and Vitamin Cmentioning

confidence: 99%

Vitamin C and oxidative stress in the seminiferous epithelium

et al. 2011

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“…Because some studies have suggested that DEHP-induced elevation of oxidative stress contributes to hepatotoxicity and testicular toxicity (23)(24)(25), the influence of oxidative stress in DEHP-induced glomerulonephritis was examined. Immunoblot analysis showed that total amounts of 4-HNE-modified proteins, a lipid peroxidation marker, were increased markedly and dosage dependently in glomeruli of DEHP-exposed PPAR␣-null mice at 22 mo but increased only mildly in exposed wild-type mice ( Figure 5A).…”

Section: Dehp Elevates Oxidative Stress In Glomerulimentioning

confidence: 99%

Peroxisome Proliferator–Activated Receptor α Protects against Glomerulonephritis Induced by Long-Term Exposure to the Plasticizer Di-(2-Ethylhexyl)Phthalate

Kamijo¹,

Hora²,

Nakajima³

et al. 2007

Journal of the American Society of Nephrology

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Safety concerns about di-(2-ethylhexyl)phthalate (DEHP), a plasticizer and a probable endocrine disruptor, have attracted considerable public attention, but there are few studies about long-term exposure to DEHP. DEHP toxicity is thought to involve peroxisome proliferator-activated receptor ␣ (PPAR␣), but this contention remains controversial. For investigation of the long-term toxicity of DEHP and determination of whether PPAR␣ mediates toxicity, wild-type and PPAR␣-null mice were fed a diet that contained 0.05 or 0.01% DEHP for 22 mo. PPAR␣-null mice that were exposed to DEHP exhibited prominent immune complex glomerulonephritis, most likely related to elevated glomerular oxidative stress. Elevated NADPH oxidase, low antioxidant enzymes, and absence of the PPAR␣-dependent anti-inflammatory effects that normally antagonize the NFB signaling pathway accompanied the glomerulonephritis in PPAR␣-null mice. The results reported here indicate that PPAR␣ protects against the nephrotoxic effects of long-term exposure to DEHP. , a probable endocrine disruptor, is used widely as a plasticizer for production of many types of polyvinyl chloride (PVC) consumer products. DEHP provides PVC items with the desired mechanical properties, including flexibility and strength. The presence of DEHP in the environment has been confirmed, as has product-related human exposure to DEHP; recent safety assessments of DEHP thereby have attracted much public interest (1). DEHP continually enters the human body via food, water, and the atmosphere. Moreover, substantial human exposure to DEHP occurs via PVC-containing medical devices that are used in intravenous therapy, enteral and parenteral nutrition support, blood transfusion, hemodialysis, cardiopulmonary bypass, and extracorporeal membrane oxygenation (2). Maximal medical exposure has been estimated to be near the US no-observed-adverse-effect level (3.7 to 14 mg/kg body wt per d). Many previous experimental animal studies yielded no obvious evidence of DEHP toxicities at these low exposure levels, but periods of exposure in the studies generally were brief. Long-term exposure to DEHP is important for safety assessment of real-world toxicity.Past experimental animal studies using short-term exposure to high-dosage DEHP have demonstrated hepatotoxicity, testicular toxicity, renal toxicity, developmental disturbance, reproductive toxicity, and teratogenicity (3-5). The peroxisome proliferator-activated receptor ␣ (PPAR␣), a member of the steroid/nuclear receptor superfamily of ligand-dependent transcription factors, has been implicated as a causative factor in these toxicities (6). PPAR␣ is expressed abundantly in the rodent liver, testis, kidney, heart, digestive tract, and retina (7) and participates in diverse physiologic functions, including maintenance of lipid and glucose homeostasis (8 -11), regulation of cell proliferation (12), and modulation of inflammatory responses (13). In humans, some ligands for this receptor, termed peroxisome proliferators, are used clinically as hypolipid...

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“…The increased generation of ROS often observed in older men [37][38][39], may be due to several factors and include routine medical prescription and environmental pollutants [58]. The generation of ROS could be made worse by infection, prolonged stasis and abnormal spermatozoa, environmental and life style changes [44,45,[59][60][61] .…”

Section: Extrinsic Factorsmentioning

confidence: 99%