Since a rare anomaly of the female genital tract was defined as uterine and vaginal duplexes with a developmental anomaly at the vaginovestibular junction, it was morphologically examined in detail in a Japanese Brown calf. The genital tract was completely duplicated from the uterus to the vagina just cranial to the vestibule. At the vaginovestibular junction, a hymenal constriction and an aberrant location of the outer urethral orifice were also observed. These anomalies suggest that an error in the complete fusion of the Müllerian ducts and a failure in the correlated development between the Müllerian ducts and the urogenital sinus occurred in the embryonic stage.

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Brucella spp. are facultative intracellular pathogens that have the ability to survive and multiply in professional and nonprofessional phagocytes, and cause abortion in domestic animals and undulant fever in humans. The mechanism and factors of virulence are not fully understood. High-affinity zinc uptake system protein mutant (znuA mutant) showed reduced growth in zinc chelated medium, and failed to replicate in HeLa cells and mouse bone marrow-derived macrophages. Transformation of znuA mutant with a shuttle vector pBBR1MCS-4 containing znuA gene restored the growth in zinc chelated medium and intracellular replication in HeLa cells and macrophages to a level comparable to that of wild-type strain. Bacterial internalization into HeLa cells and macrophages and co-localization with either late endosomes or lysosomes of znuA mutant were not different from those of wild-type strain. These results suggest that znuA does not contribute to intracellular trafficking of B. abortus, but contributes to utilization of zinc required for intracellular growth.

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The effects of 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB-126), which is the most toxic congener of coplanar polychlorinated biphenyls (Co-PCBs), on intracellular accumulation and transepithelial transport of vinblastine were examined in porcine kidney cells, LLC-PK1, and its transformant cells expressing human P-glycoprotein (LLC-MDR1). The accumulation decreased less than one-tenth in LLC-MDR1 compared to LLC-PK1. In both cells, the accumulation increased with the addition of PCB-126 and cyclosporine A (CYA), which are P-glycoprotein modulators, though the magnitudes were different in these two cell groups as well as for these two chemicals. Thus, PCB-126 might inhibit extrusion of vinblastine through the drug extrusion system as does CYA. In both the cells, there might be an endogenous drug extrusion system other than P-glycoprotein that was inhibited by CYA or PCB-126. The net basal-to-apical transepithelial transport of vinblastine increased 1.7-fold more in LLC-MDR1 than in LLC-PK1. By adding PCB-126 on the apical side, the transport was greatly decreased by -76% in the monolayer of both cells. By adding PCB-126 and CYA on the basal side in LLC-MDR1 monolayer, the transports increased -1.7-fold, so that PCB-126 might inhibit the extrusion of vinblastine on both the apical and basal sides. One of the causes to be considered for the adverse effects of Co-PCBs, in addition to the binding with an aryl hydrocarbon receptor, might be the modification of drug transport by its interaction with the drug transport system.

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Porcine interleukin-6 (PIL-6) protein without signal peptide was expressed as a glutathione S-transferase (GST) fusion protein in Escherichia coli. The fusion protein was expressed in an insoluble fraction, however, it was solubilized by refolding procedure using urea. From the solubilized protein, the recombinant PIL-6 (rPIL-6) was purified by a batch method using glutathione sepharose 4B and PreScission^TM protease cleavage. By the B3B1 hybridoma cell proliferation assay, biological activity of the purified rPIL-6 was confirmed. Three monoclonal antibodies (MAbs) named 2B-1, 5A-8 and 4C-3 were generated by using the rPIL-6 as an immunogen. Immunoglobulin isotypes of the MAbs were IgG2a (4C-3) and IgG2b (2B-1 and 5A-8). For the epitope analysis, additive enzyme-linked immunosorbent assay and immunoblot analysis using deletion mutants of PIL-6 were performed. These experiments revealed that the two MAbs (2B-1 and 5A-8) recognize an overlapped epitope and the other (4C-3) recognizes a distinct epitope, and all epitopes reside in the region of aa26-64 of PIL-6.

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The generation of multinucleated giant cells (MGC) from cells of the bovine monocyte-macrophage lineage was investigated. Freshly isolated monocytes were incubated with the conditioned medium (CM) of peripheral blood mononuclear cell cultures treated with Concanavalin A for 1-4 days (CM1 to CM4). Only CM1 generated MGC despite similar concentrations of IFNγ in all CMs. Nevertheless, MGC formation from monocytes was enhanced by adding either macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF), MGC formations from macrophages were observed only when macrophages were cultured with GM-CSF plus CM. These results indicate that several mechanisms to generate MGC from bovine monocytes-macrophage lineage cells exist, and that GM-CSF is a major mediator of MGC formation in cattle.

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This study was performed to compare acid-phosphatase staining with polymerase chain reaction (PCR) analysis for the diagnosis of Dirofilaria repens infection. The infection of D. repens was confirmed in Korean reared German shepherd dogs. Knott's tests were carried out for the detection of microfilaria in 543 Korean reared German shepherd dogs (255 females and 288 males). Eighty four of the 543 dogs (15.5%) showed microfilaria-positive reactions with the modified Knott's test, and the test-positive microfilariae were then examined by both acid phosphatase staining and PCR analysis. Six (7.1%) and 17 (20.2%) of the 84 microfilaria-positive samples, by the Knott's tests were positive to D. repens by acid-phosphatase staining and in D. repens-specific PCR analysis, respectively. All samples found to be positive by the acid-phosphatase staining were also found to be positive by PCR analysis. Therefore, we conclude that PCR analysis (20.2%) is more valuable for the diagnosis of D. repens infection than acid-phosphatase staining (7.1%) (p<0.001).

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Comparison of the QT interval and corrected QT interval values that were calculated by the methods of Bazett (QTc1) and Fridericia (QTc2) were made between dogs with or without cardiac diseases to determine the influence of the QT interval on canine heart failure. Upon comparison of the measured values on ECG between the cardiac disease and non-cardiac disease groups, it was observed that the heart rate(HR) was significantly higher in the cardiac disease group than in the non-cardiac disease group, although the QT interval was similar in the two groups. The QTc1 and QTc2 were significantly longer in the cardiac disease group than in the non-cardiac disease group. With the progression of the New York Heart Association Class, the HR tended to increase. The QTc1 and QTc2 became significantly prolonged with the progression of heart failure. Nevertheless, because Bazett's correction formula is known to overcorrect when the HR is high, it was considered that the QTc1 was actually overcorrected by high HR with the progression of heart failure. The QTc2, on the other hand, was only slightly influenced by HR, suggesting that the prolongation was due to the progression of heart failure. These results suggest that the prolongation of QTc2 in cardiac disease reflects the substantial prolongation of the QT interval without the influence of HR. It is suggested that the QTc2 could be a useful parameter for assessing the degree of heart failure in dogs with cardiac disease.

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To monitor the serum concentration of apolipoprotein C-III (apoC-III), one of the functional apoproteins in lipid metabolism, in cows with ethionine-induced fatty liver, and to investigate the association of apoC-III with liver triglyceride (TG) content and serum biochemical variables, seven nonpregnant nonlactating Holstein cows (3 to 6 years old) were used. Five cows were treated with ethionine, an analogue of methionine, (days 0, 7 and 14). The remaining two controls received saline as the vehicle. Liver TG contents in the treated cows were increased markedly whenever administered, and significant increases were observed at days 14 (666.4%, 85.3 mg/g) and 21 (675.0%, 86.4 mg/g) compared with day 0. In controls, no significant changes in liver TG content and serum biochemical variables were observed during this experiment. The serum apoC-III concentration in the treated cows was decreased drastically after the first administration and fell to the lowest value at day 10 (76.2 μg/ml, 32% of day 0). The apoC-III was significantly (p<0.05) correlated with non-esterified fatty acids (r= -0.526), γ-glutamyl transpeptidase (r= -0.407), total bilirubin (r= -0.464), positively with apolipoprotein B-100 (apoB-100, r=0.601) and cholesterol ester (r=0.449). Although apoB-100 concentrations were also reduced by the administrations, the concentrations tended to recover smoothly toward the next administration. The distinct difference in change between apoC-III and apoB-100 suggests that apoC-III may be regulated by other pathways, in addition to inhibiting the synthesis of apoproteins by ethionine.

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A three-month-old male Bull Terrier was referred to the Animal Medical Centre, Nihon University with chief complaints of subacute emesis and lethargy. Severe leukocytosis, high CRP, hypercalcemia and hypochloremia were detected. Moreover, severe calcification of gingival mucosa and abdominal skin, and abnormalities of the skeletal system were discerned. Abdominal X-ray and endoscopic examination revealed ulcer and hemorrhage on the mucosal membrane of the stomach. This might have been due to injections of high dose vitamin D at 3 and 2 weeks ago by another practioner, according to the detailed history of medication. After two months, a gastrointestinal and skin disorder disappeared, although calcification of the stomach membranes remained and abnormality of the skeletal system had worsened. Therefore, vitamin D should be carefully administrated to a puppy.

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A male miniature Dachshund, twenty-two months of age, was referred with paroxysmal generalized tremors as a main clinical sign. There were no abnormalities in the neurological examination except the lack of bilateral menace responses, and in the magnetic resonance imaging of its brain. Analysis of cerebro-spinal fluid revealed a slight rise in protein concentration and an increase in the number of cells. This case with brown hair was diagnosed as the shaker dog disease, which has also been well known as "little white shakers" syndrome due to being found in small dogs with white hair, because the clinical signs were exactly analogous to the shaker dog disease, and the generalized tremors disappeared on the first day after the administration of prednisolone and diazepam.

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Newborn calves received a low dose of bovine interferon-τ (boIFN-τ) orally for 4 weeks and calves that had developed diarrhea received a low dose of boIFN-τ orally for 5 days. No effects of boIFN-τ were seen in the duration of the diarrhea, or in daily weight gain. Calves received a high dose of boIFN-τ subcutaneously 3 times and they were then stimulated with bovine herpesvirus type 1 vaccine. No adverse effects were observed after the administration of boIFN-τ and lymphocyte subsets from calves did not change after the stimulation. Our results suggest that boIFN-τ does not seem protecting for preventing calves from diarrhea, recovering the health of calves with diarrhea or immunomodulation, although the treatment itself is not toxic.

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Three cases of pustular psoriaform dermatitis (pityriasis rosea) in pigs were clinically and histopathologically examined. Grossly, the affected skin was characterized by multiple, circumscribed lesions. Three pigs were the descendants derived from the same Landrace boar. Skin lesions expanded centrifugally to became ring-shaped plaques. There were no abnormal values in hematological and serum biochemical profiles. Histopathologically, the epidermis showed remarkable thickening. The dermal lesions were characterized by a prominent component of superficial and deep perivascular infiltration of eosinophils. Dilatation of microvasculature was accompanied with congested vessels. These results revealed that the etiology of pustular psoriaform dermatitis in pigs was associated with a hereditary predisposition derived from the specific boars. This dermatosis is histopathologically characterized by microcirculatory disturbances with infiltration of abundant eosinophils.

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An 8-year and 6-month-old female Maltese dog showed a stoop with rigidity of her cervix and back. Neurologic examination showed loss of proprioception, and deficiency of pain response. Postmortem examination revealed the neoplastic mass replacing the central area in the cervical spinal cord at the level from 4th to 5th segments. Histologically, the mass was composed of neoplastic ependymal cells. The neoplastic cells showed marked atypism, and occasionally formed ependymal rosettes. Based on the morphologic features, the tumor was diagnosed as anaplastic ependymoma. Immunohistochemistry showed that the neoplastic cells were negative for glial fibrillary acid protein, and slightly positive for vimentin and cytokeratin.

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Effects of various selective phosphodiesterase (PDE) inhibitors on muscle contractility and cyclic nucleotide contents in guinea pig taenia coli were investigated. Forskolin and sodium nitroprusside inhibited carbachol (CCh)-induced contraction in a concentration-dependent manner. Various selective PDE inhibitors, vinpocetine (type 1), erythro -9-(2-hydroxy-3-nonyl)adenine (EHNA, type 2), milrinone (type 3), Ro20-1724(type 4) and zaprinast (type 5) inhibited CCh-induced contraction in a concentration-dependent manner, but the inhibition of milrinone was noticeably smaller than that of the other PDE inhibitors. The rank order of potency was zaprinast > vinpocetine > EHNA > Ro20-1724 > milrinone. In the presence of CCh (0.3 μM), vinpocetine and Ro20-1724 both increased cAMP content, but not cGMP. By contrast, EHNA and zaprinast both increased cGMP content, but not cAMP. Pretreatment with ODQ (30 μM), a soluble guanylyl cyclase inhibitor, decreased the inhibition of CCh-induced contraction by EHNA or zaprinast. Pretreatment with SQ22536 (100 μM), an adenylyl cyclase inhibitor, decreased the inhibition of CCh-induced contraction by vinpocetine or Ro20-1724. In conclusion, it was indicated that vinpocetine- or Ro20-1724-induced relaxation was correlated with cAMP but EHNA- or zaprinast- induced relaxation was correlated with cGMP.

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To compare the antiangiogenic effects of tetraarsenic oxide (As₄O₆) with those of diarsenic oxide (As₂O₃) in the rat cornea, rat cornea micropocket assay was conducted to induce angiogenesis by implantation of the pellet contained 1.0 ng of nerve growth factor (NGF). Ten of thirty eyes of Sprague-Dawley rats were randomly assigned to one of three groups, namely, control group (no medication), As₂O₃ group (50 mg/kg As₂O₃, PO, s.i.d.), and As₄O₆ group (50 mg/kg As₄O₆, PO, s.i.d.). After implantation, the number of new vessels, vessel length and clock hour of neovascularization were examined under the microscope from day 3 to day 7. The area of neovascularization was calculated using a mathematical formula. Although new vessels in control and As₂O₃ groups were first noticed at day 3, whereas those of As₄O₆ group were first observed on day 5. The number, length, clock hour of neovascularization and areas of the vessels in As₄O₆ group showed more significant inhibition than those of control and As₂O₃ groups from day 5 (P<0.05). However, there were no differences in all parameters between control group and As₂O₃ group during the entire study period. These results showed that As₄O₆ had antiangiogenic effects on the new vessels induced by NGF in the rat cornea.

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Females of the inbred mouse RR strain have a limited ability to nurture their offspring, and frequently the young die during rearing. We previously identified a significant quantitative trait locus (QTL) responsible for the inferior nurturing ability on chromosome 5 (Naq1), on the basis of litter weight of six pups at days 7, 12, and 21 after parturition. Here, we carried out further mapping of Naq1 to define the confidence interval precisely. At the same time, we analyzed new quantitative trait variables, litter weight gain between days 7 and 12 (WG1), and that between days 12 and 21 (WG2), to characterize further the physiology of inferior nurturing ability. Consequently, a peak LOD score for the Naq1 was identified on D5Mit218 (72 cM), which was located approximately 2 cM distal to our previous expectation, as a significant QTL for WG1 (LOD 5.5), but not for WG2 (LOD 0.9). Because the growth of pups depends purely on milk obtained from the dam up to day 12 after birth, it seems possible to assume that the inferior nurturing ability in RR mice is related to defects in maternal nutritional support (that is, lactation) rather than to defects in pup growth. Naq1 is a novel QTL as far as the QTL results of relevant female reproductive traits in cattle and pigs are concerned.

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Body weight quantitative trait loci (QTLs), Bwq1 and Bwq2, identified previously in C57BL/6J × KK-A^y/a F₂-A^y/a mice, were further confirmed and characterized. Body weight measurement was done from 21 days after birth (Day 21) through Day 100, at 10-day intervals. Bwq1 was statistically significant only on Days 40, 50, and 60, whereas Bwq2 was statistically significant on and after Day 40. When body weight gain (WG) between two successive weight measurements was evaluated, both Bwq1 and Bwq2 were statistically significant only for WG between Days 30 and 40. The results suggest that variations in body weight among F₂-A^y/a individuals in later life have been determined by variations in WG during the period shortly after weaning. The results also suggest that Bwq1 is related to increased body weight in the KK strain, because the effect of Bwq1 on the body weight is observed not only in F₂-A^y/a, but also in F₂-a/a. On the other hand, it is suggested that Bwq2 is related to enhanced obesity caused by A^y mutation and therefore is a genetic modifier that specifically interacts with the A^y allele, because the effect of Bwq2 is only observed in F₂-A ^y/a. There are two candidate genes, Pparg and Hrh1, which are located near the 95% confidence interval of Bwq2, and which are expressed in the adipose tissue; however, we could not find any nucleotide differences in both cDNAs between KK and C57BL/6J strains.

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Growth hormone (GH) is secreted in a pulsatile manner, but the underlying mechanisms of GH pulse generation remain to be resolved. In the present study, we investigated the relationship between GH pulses in the peripheral circulation and GH-releasing hormone (GHRH) and somatostatin (SRIF) profiles in the cerebrospinal fluid (CSF) of male goats. The effects of an intracerebroventricular (icv) injection of neuropeptide Y (NPY), galanin and ghrelin were also analyzed. Blood and CSF samples were collected every 15 min for 8 hr from the jugular vein and third ventricle, respectively. GH pulsatility in the goat was found to consist of distinct large pulses of 5 hr periodicity and small pulses of 1 hr periodicity. GHRH and SRIF in the CSF fluctuated in a pulsatile manner with 1 hr periodicity, and most of the descending phase of SRIF pulses were associated with the initiation of GH pulses. Icv injections of NPY, galanin and ghrelin stimulated GHRH release without affecting SRIF release. In addition, NPY suppressed, and galanin and ghrelin induced large GH pulses, although ghrelin was much more effective than galanin. These results suggest that an hourly fall in SRIF is involved in generating intrinsic circhoral rhythm of GH pulsatility. The mechanisms underlying the generation of large GH pulses of 5 hr periodicity remain unknown, while direct action of NPY and/or ghrelin on the pituitary might be involved.

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The hypogonadic rat (hgn/hgn) shows male sterility, reduced female fertility, and renal hypoplasia, controlled by a single recessive gene located on rat chromosome 10. We developed a fine map around the hgn locus using 565 rat backcross progeny and a Rat/Hamster radiation hybrid panel. The hgn locus was linked to Aldoc (aldolase c) and whn (winged helix of nude), and located in a 0.34-cM region between D10Rat30 and D10Rat68. The distance of the region was approximately 840-kb on rat physical map. Neither loci responsible for male sterility nor renal hypoplasia has been mapped on the homologous regions of mouse chromosome 11 and human chromosome 17. Identification of the gene responsible for the hgn mutation would provide important information on urogenital development.

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The effects of cyclic AMP increasing cardiotonics (dopamine, dobutamine, amrinone and milrinone) on the blood flow in most organs were compared using colored microsphere technique in isoflurane-anesthetized dogs. Dopamine increased blood flow in ventricular myocardium. Furthermore dopamine induced the increase in blood flow in intestine and kidney at low to middle dose, but not at high dose. Dobutamine induced the highest increase in blood flow in ventricular myocardium and skeletal muscle among the drugs evaluated at middle and high doses. Amrinone and milrinone increased blood flow in ventricular myocardium almost same with catecholamines, and milrinone decreased vascular resistance moderately in most other organs. Milrinone might be more useful than catecholamines for improvement of congestive heart failure or peripheral circulatory failure accompanied with exceeded vasoconstriction.

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An eighteen month old female Doberman pinscher dog was referred to teaching hospital of Adnan Menderes University, Faculty of Veterinary Medicine with the complaint of right forelimb lameness for a month. On the basis of clinical, radiographical, scintigraphical, computed tomographical and histopathological findings, aneurysmal bone cyst was diagnosed. Surgical curettage and bone cement treatment were applied. The patient recovered after 12 months. This case proves that aneurysmal bone cyst, without osteolysis and/or damages to the surrounding tissues, may result in a good prognosis if curettage and treatment with bone cement are done.

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Odontogenic cysts, which showed cystic radiolucency in the jaw bone by radiographic examination and computed tomography, were enucleated by operation in 3 dogs. One dog had a odontogenic keratocyst in the incisive bone of the right maxilla and another 2 cases revealed dentigerous cysts in the mandible. These cyst walls were enucleated or transpired by semiconductor laser. Afterwards, osteogenesis was confirmed at the defective part of jaw bone by extirpation of the cyst in all cases, and no recurrence has been noted in any cases. Odontogenic cyst is a disease which should be treated by surgical extirpation or transpiration.

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Several studies have reported that the plasma testosterone (T) level and semen volume are compensated after hemicastration (HEC) in adult dogs, but that the sperm count is not. Nevertheless, the effects of HEC in prepubertal dogs have not been reported. In this study, HEC was performed at 16 weeks of age in 8 male beagles, and the function of the residual testis was investigated until 48 weeks of age. The testis volume was consistently higher in the HEC group than the control (CON) group. After 40 weeks of age, compensatory hypertrophy was observed, with a mean testis volume of 125% of that in the CON group (p<0.05). Furthermore, the semen volume and plasma testosterone (T) level were similar to those in the CON group, suggesting functional compensation, but the sperm count was not compensated. These results showed that the testis volume, semen volume, and plasma T level were compensated after HEC in prepubertal dogs, but the spermatogenic function was not.

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The relationship between the disappearance of glycoproteins from the surface of canine sperm and sperm capacitation was investigated in vitro. The protease (PR) concentration in flush fluids of the uterine horns and oviducts removed from 6 estrous, 5 diestrous, and 5 anestrous bitches was measured with a protease assay kit. Ejaculated sperm collected from 10 dogs were incubated for 4 hr in Eagle's MEM supplemented with 1 or 5 μg/ml PR, or to which no PR had been added (control). The glycoproteins on the surface of the sperm were stained with 4 different FITC-lectins (Con A, PHA-E, PNA, and WGA), and the percentages of hyperactivated (HA-) sperm and acrosome-reacted (AR-) sperm were evaluated. The mean PR concentration (5.95 μg/ml) in the flush fluid from the oviducts of the estrous bitches was significantly higher than in the fluid from their uterine horns (1.00 μg/ml; P<0.01). The PR concentrations of the flush fluids from the uterine horns and oviducts of both the diestrous and anestrous bitches were less than 0.05 μg/ml. Before incubation the acrosomal regions or entire heads of all sperm clearly stained with each FITC-lectin, but the percentages of sperm binding the 4 FITC-lectins decreased after incubation. The percentages of lectin-binding sperm in the MEM containing 5 μg/ml PR were significantly lower than in the control MEM (P<0.05 and 0.01). The mean percentages of motile sperm and HA-sperm after incubation in the MEM with PR were higher than in the control MEM, but there were no differences in the percentages of AR-sperm. The results indicate that HA-movement of sperm is induced by the disappearance of glycoproteins from the surface of canine sperm as a result of the action of PR in the oviductal fluid of estrous bitches.

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The spermatogenic function and plasma testosterone (T) level in the sex maturation process were investigated as to 180 mixed breed cats ranging from 4 months to 2 years in age to be castrated. Testis/epididymis weights reached a peak at 10 and 8 to 9 months of age, respectively. In the testis, sperm appeared at 5 months of age. At 7 months of age, sperm were observed in 96.2% of the cats. In the tail of the epididymis, sperm appeared in 46.9% of the cats at 6 months of age and in all cats at 8 or more months of age. Furthermore, the mean plasma T level rapidly increased at 8 months of age, and reached a peak (2.64 ± 0.68 (SE) ng/ml) at 10 months of age. Three of 180 cats (1.67%) had unilateral cryptorchidism. These results suggest that the spermatogenic function in male cats becomes mature at 8 to 10 months of age.

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The breeding season was investigated in 174 female cats that were acclimated under a natural photoperiod, and determined the interval between birth and initial estrus (puberty) was determined in 125 cats. Although the breeding season differed noticeably among individual animals, the mean was 180.4 ± 3.0 (SE) days between the end of January and the end of July. The interval between birth and first estrus ranged from 181 to 560 days, with a mean of 345.0 ± 0.9 days. With respect to month of birth, the mean interval was 343.0 ± 9.5 days in cats born between March and June. Among cats that were born between July and October, the mean intervals were 242.0 ± 6.3 days in cats that exhibited estrus the year after birth and 519.2 ± 5.8 days in those that exhibited estrus 2 years after birth.

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Unilateral intrauterine horn insemination (UIUI) was carried out in cats, and we investigated the fertilization rate of ova ovulated from the contralateral ovary. Various numbers of sperm were used to inseminate the uterine horn on the side where ovulation was inhibited. The rates of conception were 1/11 (9.1%), 2/11 (18.2%), and 5/7 (71.4%) in the 2 × 10⁶, 4 × 10⁶, and 8 × 10 ⁶ groups, respectively. Furthermore, the fertilization rate was 70.7% in the 8 × 10⁶ group. Thus, ova ovulated from the contralateral ovary were not fertilized or the fertilization rate was low in some cats even when UIUI was performed with a large number of sperm.

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Di-(2-ethylhexyl) phthalate (DEHP), a peroxisome proliferator-activated receptor α (PPARα) ligand, alters the lipid composition of rat testis, yet the mechanism is unclear. In this study, we investigated the effect of DEHP on the synthesis and metabolism of arachidonic acid (AA), a precursor of eicosanoids, in the testis of prepubertal rats. DEHP (100 and 1,000 mg/kg, 5 days) administration caused a significant reduction in activity of cytosolic phospholipase A₂ (cPLA₂), the rate-limiting enzyme in the AA and eicosanoid synthesis pathways. DEHP increased the expression of 12-lipoxygenase (12-LOX) in rat testis, whereas cyclooxygenase-2 (COX-2) expression was not altered. Cytochrome P450 4A1 (CYP4A1), a product of a PPARα-regulated gene, was markedly increased in the testis by DEHP administration. Taken together, DEHP suppresses cPLA₂ activity and induces the AA metabolizing enzymes such as 12-LOX and CYP4A1, resulting in the reduction of AA level. These data suggest that altered AA metabolic cascades may be related to the decrease of testosterone concentration in DEHP-induced testicular atrophy.

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