Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral administration of di(2-ethylhexyl)phthalate (DEHP) at 1000 mg/kg body weight to adult male albino rats maintained on low protein (LP) diet for 15 d resulted in a greater decrease in absolute and relative weights of the testis and in epididymal sperm count than in those rats maintained on a normal protein (NP) diet. A marked increase in the activity of testicular beta-glucuronidase and gamma-glutamyl transpeptidase (GGT) in the LP-fed animals suggested that LP diet enhanced the vulnerability of Sertoli cells towards DEHP. A greater decrease in the activity of testicular acid phosphatase, lactate dehydrogenase isoenzyme-X (LDH-X) and sorbitol dehydrogenase (SDH) in the LP-fed animals occurred in comparison to NP-fed animals. Degeneration of mature germinal cells in the LP-fed animals on exposure to DEHP suggested that LP diets enhance the susceptibility of the testis towards DEHP.
 ...
PMID:The influence of low protein diet on the testicular toxicity of di(2-ethylhexyl)phthalate. 136 64

In utero exposure to di(2-ethylhexyl)phthalate (DEHP; 1000 mg/kg body weight) significantly decreased activities of testicular sorbitol dehydrogenase and acid phosphatase and increased gamma-glutamyl transpeptidase, lactate dehydrogenase and beta-glucuronidase activities at early ages. A decrease in the sperm count of the epididymal spermatozoa was also observed in the sexually matured animals of DEHP exposed group. The data suggest that in utero exposure to DEHP may affect the normal development of testes.
 ...
PMID:Effect of in utero exposure to di(2-ethylhexyl)phthalate on rat testes. 181 82

Oral administration of di(2-ethylhexyl)phthalate (DEHP) in doses of 250, 500, 1000 and 2000 mg/kg to adult rats for 15 days caused a significant dose dependent decrease in the sperm count of the epididymal spermatozoa. The activity of gamma-glutamyl transpeptidase (gamma GT) and lactate dehydrogenase (LDH) was significantly increased in the animals of the treated groups. An increase in the activity of beta-glucuronidase and decrease in the activity of acid phosphatase was also observed at the highest dose of DEHP. The activity of sorbitol dehydrogenase (SDH) was found to be decreased in the animals exposed to 1000 and 2000 mg/kg of DEHP. These results suggest that DEHP can affect spermatogenesis by altering the activities of the enzymes responsible for the maturation of sperms. The reduced number of sperms may be responsible for the antifertilic effects of DEHP.
 ...
PMID:Effect of di(2-ethylhexyl)phthalate (DEHP) on spermatogenesis in adult rats. 287 65

In mammals, exposure to antiandrogenic chemicals during sexual differentiation can produce malformations of the reproductive tract. Perinatal administration of AR antagonists like vinclozolin and procymidone or chemicals like di(2-ethylhexyl) phthalate (DEHP) that inhibit fetal testicular testosterone production demasculinize the males such that they display reduced anogenital distance (AGD), retained nipples, cleft phallus with hypospadias, undescended testes, a vaginal pouch, epididymal agenesis, and small to absent sex accessory glands as adults. In addition to DEHP, di-n-butyl (DBP) also has been shown to display antiandrogenic activity and induce malformations in male rats. In the current investigation, we examined several phthalate esters to determine if they altered sexual differentiation in an antiandrogenic manner. We hypothesized that the phthalate esters that altered testis function in the pubertal male rat would also alter testis function in the fetal male and produce malformations of androgen-dependent tissues. In this regard, we expected that benzyl butyl (BBP) and diethylhexyl (DEHP) phthalate would alter sexual differentiation, while dioctyl tere- (DOTP or DEHT), diethyl (DEP), and dimethyl (DMP) phthalate would not. We expected that the phthalate mixture diisononyl phthalate (DINP) would be weakly active due to the presence of some phthalates with a 6-7 ester group. DEHP, BBP, DINP, DEP, DMP, or DOTP were administered orally to the dam at 0.75 g/kg from gestational day (GD) 14 to postnatal day (PND) 3. None of the treatments induced overt maternal toxicity or reduced litter sizes. While only DEHP treatment reduced maternal weight gain during the entire dosing period by about 15 g, both DEHP and DINP reduced pregnancy weight gain to GD 21 by 24 g and 14 g, respectively. DEHP and BBP treatments reduced pup weight at birth (15%). Male (but not female) pups from the DEHP and BBP groups displayed shortened AGDs (about 30%) and reduced testis weights (about 35%). As infants, males in the DEHP, BBP, and DINP groups displayed femalelike areolas/nipples (87, 70, and 22% (p < 0.01), respectively, versus 0% in other groups). All three of the phthalate treatments that induced areolas also induced a significant incidence of reproductive malformations. The percentages of males with malformations were 82% (p < 0.0001) for DEHP, 84% (p < 0.0001) for BBP, and 7.7% (p < 0.04) in the DINP group. In summary, DEHP, BBP, and DINP all altered sexual differentiation, whereas DOTP, DEP, and DMP were ineffective at this dose. Whereas DEHP and BBP were of equivalent potency, DINP was about an order of magnitude less active.
 ...
PMID:Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. 1109 47

Several members of the phthalate ester family have antiandrogenic properties, yet little is known about how exposure to these ubiquitous environmental contaminants early in development may affect sexual development. We conducted experiments to determine effects of in utero and lactational exposure to the most prevalent phthalate ester, di(2-ethylhexyl) phthalate (DEHP), on male reproductive system development and sexual behavior. Sprague-Dawley rats were dosed with corn oil or DEHP (0, 375, 750, or 1,500 mg/kg/day, per os) from gestation day 3 through postnatal day (PND) 21. Dose-related effects on male offspring included reduced anogenital distance, areola and nipple retention, undescended testes, and permanently incomplete preputial separation. Testis, epididymis, glans penis, ventral prostate, dorsolateral prostate, anterior prostate, and seminal vesicle weights were reduced at PND 21, 63, and/or 105-112. Additional dose-related effects included a high incidence of anterior prostate agenesis, a lower incidence of partial or complete ventral prostate agenesis, occasional dorsolateral prostate and seminal vesicle agenesis, reduced sperm counts, and testicular, epididymal, and penile malformations. Many DEHP-exposed males were sexually inactive in the presence of receptive control females, but sexual inactivity did not correlate with abnormal male reproductive organs. These results suggest that in utero and lactational DEHP exposure also inhibited sexually dimorphic central nervous system development. No major abnormalities were found in any of eight control litters, but DEHP caused severe male reproductive system toxicity in five of eight litters at 375 mg/kg/day, seven of eight litters at 750 mg/kg/day, and five of five litters at 1,500 mg/kg/day. These results demonstrate that the male reproductive system is far more sensitive to DEHP early in development than when animals are exposed as juveniles or adults. The effects of DEHP on male reproductive organs and sexual behaviors and the lack of significant effects on time to vaginal opening and first estrus in their littermates demonstrate that DEHP (and/or its metabolites) affects development of the male reproductive system primarily by acting as an antiandrogen. The pattern of effects of in utero and lactational DEHP exposure differed from patterns caused by other phthalate esters, and the preponderance of anterior prostate agenesis appears to be unique among all chemicals. These results suggest that DEHP acts partly by mechanisms distinct from those of other antiandrogens.
 ...
PMID:Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer Di(2-ethylhexyl) phthalate. 1133 83

Linuron is an herbicide that displays weak androgen receptor antagonist activity. Male offspring exposed in utero to 50 mg/kg/day linuron often exhibit malformations in Wolffian duct derivatives (i.e. the epididymis and vas deferens). The objectives of this study were to determine the point during the perinatal period that linuron-induced epididymal lesions can be identified, to characterize linuron-mediated perinatal testicular and epididymal pathology, and to determine whether male rat fetuses exposed prenatally to linuron exhibit decreased intratesticular and serum testosterone (T) levels. Pregnant rats were administered corn oil vehicle or linuron by gavage at 0 or 50 mg/kg/day (n = 3 controls, 5-11 linuron-treated dams per time point) from gestation days (GD) 12 to 21 or to termination. Male fetuses or offspring were necropsied on GD 17, 19, and 21, and postnatal days (PND) 7 and 14. Epididymal malformations were not observed in fetuses from linuron-treated dams but were seen in linuron-exposed male offspring on PND 7 and 14. No testicular lesions were observed at any time point. The growth and development of linuron-exposed fetuses were altered, as evidenced by slight decreases in fetal weight and increased levels of immunoreactive proliferating cell nuclear antigen (PCNA) on GD 21. Intratesticular and serum T levels were not decreased in linuron-exposed male fetuses. These findings indicate that the adversely altered adult phenotype following in utero exposure to linuron is very similar to that produced by the antiandrogens di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP). However, the absence of testicular lesions or alterations in fetal testosterone levels would suggest that the effect of linuron on the developing Wolffian ducts is distinctly different from DBP or DEHP.
 ...
PMID:Effects of in utero linuron exposure on rat Wolffian duct development. 1195 44

Phthalates are chemicals used in many industrial products (plastic toys, shampoos, soaps), and are suspected of inducing adverse effects on the male reproductive system. In the present study, we evaluated the effects of the plasticizer di-(2-ethylhexyl)-phthalate (DEHP) on the reproductive function and sexual behavior of male offspring rats, exposed in utero and during lactation (0, 20, 100 and 500 mg/kg per day by gavage). The effects produced clearly demonstrate the ability of DEHP to disrupt the androgen-regulated development of the male reproductive tract. Absolute and relative weights of androgen-dependent tissue organs (ventral prostate and seminal vesicle) were significantly reduced at the highest dose level tested (500 mg/kg per day). Impairment of male sexual behavior (500 mg/kg per day) was also observed. Moreover, the reduction in daily sperm production and epididymal sperm counts observed after administration of the highest dose suggests an impairment of the spermatogenic processes. Most of the adverse effects reported here were observed both during puberty and during adulthood, indicating permanent effects of in utero and lactational DEHP exposure.
 ...
PMID:Phthalate affect the reproductive function and sexual behavior of male Wistar rats. 1686 86

In order to comparatively assess the systemic toxicity and sperm parameters, nine phthalate diesters, including di(2-ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), di-n-octyl phthalate (DnOP), diethyl phthalate (DEP), butylbenzyl phthalate (BBP), dimethyl phthalate (DMP), di-isodecyl phthalate (DIDP), diundecyl phthalate (DUP), and di-isononyl phthalate (DINP), and five phthalate monoesters, including mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBuP), monobenzyl phthalate (MBeP), monoethyl phthalate (MEP), monomethyl phthalate (MMP), and phthalic acid (PA) were administered orally to Sprague-Dawley male rats at 250 (phthalate monoesters and PA) or 500 mg/kg body weight (bw)/d (phthalate diesters) for 4 wk. Liver weights were significantly increased in g roups treated with DEHP, DBP, BBP, DIDP, DINP, MEHP, and MBuP compared to the control. Testes weights were significantly reduced only in DEHP, DBP, and MEHP-treated groups compared to the control. Significant decreases in red blood cell (RBC) and hematocrit (Ht) levels were observed in DEHP-treated rats, whereas significant increases in mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and platelet (PLT) levels were found in the DEHP-treated group. Hemoglobin (Hb) level was reduced only in the DMP group. Similar to effects on testis and epididymal weights, DEHP and MEHP significantly reduced sperm numbers and motility. In particular, DnOP, DBP, BBP, MEP, MBuP, DUP, DINP, and MBeP significantly lowered the sperm counts and sperm motility of epididymal sperm, detected by a change in the sperm motion parameters. The strongest to the weakest adverse effects for sperm motility were as follows: DEHP > DBP > DnOP > DUP > DIDP > BBP among diesters and MBuP > MEP > MEHP among monoesters, respectively. These results suggest that the adverse effects of phthalate esters (PEs) on sperm parameters in male rats are greater with phthalate diesters than monoesters, which may be useful for the risk assessment of phthalates.
 ...
PMID:Comparative toxicological evaluation of phthalate diesters and metabolites in Sprague-Dawley male rats for risk assessment. 2007 17

The di(2-ethylhexyl) phthalate (DEHP) is an ubiquitous environmental chemical with detrimental health effects. The present work was designed to asses some potential mechanisms by which DEHP causes, among others, a reduced body fat retention. Since this effect could be related to an alteration of adipocyte triacylglycerol (TG) metabolism, we evaluated the effects of dietary DEHP in adipose tissues upon (1) the number and size of fat cells; (2) the basal and stimulated lipolysis and (3) the lipoprotein lipase (LPL) activity. Groups of male Wistar rats were fed for 21 days a control diet alone (control group) or the same control diet supplemented with 2% (w/w) of DEHP (DEHP group). The LPL activity of DEHP-fed rats was increased in lumbar and epididymal adipose tissues. These rats had significantly reduced weight in epididymal and lumbar tissues, together with reduced size of epididymal adipocytes. These alterations do not seem to be associated with higher lipid mobility because neither basal lipolysis nor 'in vitro' stimulated lipolysis by noradrenaline (NA) showed to be modified by DEHP. Based on these results, we concluded that the adipose tissue size reduction induced by DEHP intake is not due to changes in lipolysis nor to a decreased LPL activity. More research is needed to achieve a comprehensive understanding of the potential mechanisms by which DEHP causes, among others, a reduced body fat retention.
 ...
PMID:Effect of di(2-ethylhexyl) phthalate (DEHP) on lipolysis and lipoprotein lipase activities in adipose tissue of rats. 2014 57

Several phthalate esters have been linked to the Phthalate Syndrome, affecting male reproductive development when administered to pregnant rats during in utero sexual differentiation. The goal of the current study was to enhance understanding of this class of compounds in the Sprague Dawley (SD) fetal rat following exposure on gestational days (GDs) 14-18 by determining the relative potency factors for several phthalates on fetal testes endpoints, the effects of a nine phthalate mixture on fetal testosterone (T) production, and differences in SD and Wistar (W) strain responses of fetal T production and testicular gene expression to di(2-ethylhexyl) phthalate (DEHP). We determined that diisobutyl phthalate (DIBP) and diisoheptyl phthalate (DIHP) reduced fetal testicular T production with similar potency to DEHP, whereas diisononyl phthalate (DINP) was 2.3-fold less potent. DINP was also less potent at reducing StAR and Cyp11a gene expression levels, whereas DIBP was slightly more potent than DEHP. We observed that administration of dilutions of a mixture of nine phthalates (DEHP, DIHP, DIBP, dibutyl-, benzyl butyl-, dicyclohexyl-, diheptyl-, dihexyl-, and dipentyl phthalate) reduced fetal T production in a dose-dependent manner best predicted by dose addition. Finally, we found that the differential effects of in utero DEHP treatment on epididymal and gubernacular differentiation in male SD and W rats (0, 100, 300, 500, 625, 750, or 875 mg DEHP/kg/day) are likely due to tissue-specific strain differences in the androgen and insl3 signaling pathways rather than differential effects of DEHP on fetal testis T and insl3 production.
 ...
PMID:Dose-response assessment of fetal testosterone production and gene expression levels in rat testes following in utero exposure to diethylhexyl phthalate, diisobutyl phthalate, diisoheptyl phthalate, and diisononyl phthalate. 2163 15


1 2 Next >>