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Oxidative stress in testes of rats subjected to chronic iron intoxication and alpha-tocopherol supplementation.

Oxidative stress parameters were evaluated in rat testes after chronic iron intoxication and vitamin E supplementation. Male Wistar rats were fed during 6 weeks with the following diets: C = rat chow; I = C + 25 mg carbonyl-iron/g diet; A = C + 0.2 mg alpha-tocopheryl acetate/g diet; and the combination of I and A (IA). After the treatment, no changes in final body weight, testis weight and protein content were observed. Total iron content in testes from the I group was 33% higher compared to the C group (216 +/- 10 nmol/g of tissue). The content of alpha-tocopherol (alphaT) was 2.5-fold higher in the A and IA groups compared to the C group (12.8 +/- 0.7 nmol/g tissue). The content of ubiquinol-9 (13.0 +/- 1.7 nmol/g tissue) and ubiquinol-10 (3.3 +/- 0.5 nmol/g tissue) was similar among the groups. Superoxide dismutase activity was 13 and 16% lower in the A and IA groups with respect to the C group (12.9 +/- 0.7 U/mg protein). Catalase activity was 26 and 33% lower in the I and IA groups than in the C (0.19 +/- 0.01 pmol/mg protein) and A (0.21 +/- 0.01 pmol/mg protein) groups, respectively. Glutathione peroxidase was 24 and 23% higher in the IA group than in the C (11.4 +/- 0.3 mU/mg protein) and I (11.5 +/- 1.0 mU/mg protein) groups, respectively. The testes content of 2-thiobarbituric acid-reactive substances (TBARS) and protein-associated carbonyl groups were 37 and 16% higher, respectively, in the I group than in the C group. These increased in TBARS and carbonyls, were not observed in the IA group. No diet-associated changes were observed in the steady state levels of 8-oxo-2'-deoxyguanosine in testes DNA (4.2 +/- 0.2 residue/10(5) dG). The present data suggest that this model of chronic iron overload produced a mild oxidative damage in rat testes that was partially prevented by alphaT supplementation.

Animals↗

Effects of subchronic exposure of rats to 2-methoxyethanol or 2-butoxyethanol: thymic atrophy and immunotoxicity.

Male Sprague-Dawley rats were exposed to either 2000 or 6000 ppm of 2-methoxyethanol (ME) or 2-butoxyethanol (BE) and females were exposed to either 1600 or 4800 ppm of these compounds in the drinking water for 21 days. Body weights were decreased in male rats exposed to the high doses of both chemicals, while body weights of females exposed to either dose of BE were decreased. Male and female rats exposed to either concentration of ME had a dose-related reduction in thymus weights. Testis weight was significantly lower in male rats exposed to the high dose of ME. Dose-related increases in natural killer (NK) cell cytotoxic activities and decreases in specific antibody production were observed in all rats treated with ME. Rats exposed to the low dose of BE also had enhanced NK cell activity. Splenocyte production of interferon-gamma was decreased in male rats exposed to either dose of ME and in females treated with the high dose of ME. Spleen cell numbers were reduced in males exposed to the high dose of ME and females given either dose of ME. It appears that the immune system is a sensitive target of ME but not BE. The effects of ME on immune function differ depending on the immune parameter assessed. Enhanced NK cell activity may partially explain the observations of others that certain glycol ethers have antitumor effects in vivo.

Animals↗

Soy isoflavones modify liver free radical scavenger systems and liver parameters in Sprague-Dawley rats.

Soyfoods contain estrogenic isoflavones--namely, genistein (G) and daidzein (D)--that, like estrogens, display physiological effects in humans and animals. Previously we and others have demonstrated antioxidant and cardioprotective effects of orally ingested soy diets and soy isoflavones. The overall objective of this study was to test the effects of injected soy isoflavones, G and D, on liver lipids, liver free radical scavenger systems, and parameters of cardiovascular risk. Forty male rats were injected with G, D, estradiol (E), or a vehicle control (V) for 6 weeks. At the end of the study, body weight, food intake, feed efficiency ratio (FER), plasma glucose and cholesterol, abdominal fat pad weight, reproductive organ weight, liver weight, liver lipids, and liver free radical scavenger systems were compared. Food intake was significantly (P < .04) higher in the D-, G-, and E-treated animals compared with V-treated animals. FER was lower (P < .001) in D-, G-, and E-treated animals compared with the V- and the E-treated animals. Body weight, testis weight, and prostate weight were markedly (P < .001) lower in the E-treated animals compared with D-, G-, and V-treated animals. Intraabdominal fat pad weights were also significantly (P < .001) lower in the E group, although this effect was lost when corrected for body weight. Liver weights were considerably lower in the D-, G-, and E-treated animals versus the V group (P < .001). Total plasma cholesterol was reduced (P < .05) in D- and E-treated animals versus the V group. Liver lipids appeared to be unchanged by the isoflavones and slightly elevated by E treatment (P < .02). Liver catalase levels were numerically higher in the D- and E-treated animals compared with the V group (P < .1). Similarly, Cu/Zn superoxide dismutase (SOD) activity was significantly elevated in the D and E groups (P < .01), while G treatment (P < .03) elevated SOD to a lesser degree, versus the V group. These results suggest that subcutaneous injections of the naturally occurring soy isoflavone D and, to a lesser extent, G exert cardioprotective effects and stimulate antioxidant systems, while minimizing the undesirable effects elicited by E treatment.

Animals↗

Pachytene pairing in relation to sperm and oocyte numbers in a male-fertile reciprocal translocation in the mouse.

In adult males carrying the male-fertile reciprocal translocation T(2;4)13H, body weights, testis weights, and sperm counts were higher in heterozygotes than in homozygotes. Heterozygotes whose mothers were C3H/He exceeded their reciprocal counterparts in the same criteria. At 3-4 days of age, no significant differences between homozygous and heterozygous females were found in body weight, ovarian volume, or oocyte numbers, although mean oocyte volumes were somewhat larger in heterozygotes than in homozygotes. In homozygous males and females the synaptonemal complexes of rearranged chromosomes appeared as bivalents that were indistinguishable from normal bivalents. In most gametocytes of heterozygotes, the translocation was present in the form of a quadrivalent. The degree of pairing failure was greater in oocytes than in spermatocytes. Terminal asynapsis of quadrivalents was very rare in spermatocytes, but it affected one quarter of the oocytes. Only very few translocation configurations were associated with the XY bivalent. It is concluded that the number of sperm produced in male heterozygotes can match the general increase in vigor by the formation of a high level of fully paired quadrivalents, whereas a greater degree of terminal asynapsis in the quadrivalents of oocytes may indicate a slightly more deleterious effect of this translocation on oogenesis.

Animals↗

Effects of ethanol treatment on Leydig cellular NADPH-generating enzymes and lipid profiles.

Effects of ethanol treatment on Leydig cell NADPH-generating enzymes and lipid profiles were studied. Ethanol treatment (3.0 g/kg b.wt.) twice daily as a 25% (v/v) aqueous solution given to adult Wistar rats reduced the body weight, testis weight and relative weights of the seminal vesicles and ventral prostate. Serum LH and testosterone were also decreased. Similarly, the NADPH-generating enzymes such as G-6-PDH, 6-PGDH, NADP-ICDH were reduced, but malic enzyme was unaltered. Leydig cell total lipid was decreased: neutral lipids such as esterified cholesterol and triacyl glycerol were decreased but free cholesterol and diacyl glycerol were increased. The reduction in total phospholipid was contributed to by fractions such as phosphatidyl inositol, phosphatidyl serine, phosphatidyl choline and phosphatidyl ethanolamine. Withdrawal of ethanol treatment for 30 days restored these to the normal level. The present findings suggest that the ethanol treatment impairs Leydig cellular NADPH generation which may be one of the biochemical mechanisms mediating the direct and indirect effects of ethanol resulting in hypoandrogenization.

Animals↗

[Effects of phoxim on sperm production and motility of rats].

The effects of phoxim at various dosage levels on sperm production and motility in rats were studied. Sperm motility was measured by computer assisted sperm analysis (CASA). The results showed that rats exposed to phoxim at higher doses(24.5 and 73.5 mg/kgBW) for 60 successive days showed significant reduction of daily sperm production as compared with the control (P < 0.05, P < 0.01). Sperm motion parameters such as currilinear velocity (VCL), straight line velocity(VSL), beat cross frequency(BCF), linearity(LIN) and straightness(STR) were significantly decreased than those of the control(P < 0.05, P < 0.01) which indicated a dose-dependent relationship to some extent. However, there was no obvious change in body weight, testis weight and the rate of motile sperm in epididymis. It suggests that the male reproductive toxicilIty of phoxim at higher doses (24.5 and 73.5 mg/kgBW) mainly induces a reduction of sperm production and motility.

Animals↗

Effects of oyster extract on the reproductive function of zinc-deficient mice: bioavailability of zinc contained in oyster extract.

Zinc is a vital nutrient in the normal reproductive function and embryonic development of mammals, and it is well known that oyster extract contains significant amounts of zinc. The effects of oyster extract on reproductive function, such as embryonic development, serum levels of zinc and sperm maturation were examined in zinc-deficient mice. Zinc deficiency in dams during pregnancy induced a decrease in the successful pregnancy rate, maternal weight gain, the number of live fetuses and fetal body weight. Zinc deficiency for 12 weeks in male mice induced a decrease in body weight, testis weight and sperm count in the epididymis. However, reproductive failure, embryonic defects and decreased sperm motility in zinc-deficient mice were improved by supplementation with oyster extract. Some nutrients contained in oyster extract, such as taurine and glycogen, may be related to the recovery of reproductive function. There were significantly lower serum concentrations of zinc in dams fed a zinc-deficient diet. However, the serum zinc concentration was normal in the oyster extract-supplemented group. No difference in the concentration of serum zinc was observed between the oyster extract- and zinc carbonate-supplemented groups. From these findings, it is suggested that oyster extract is a useful supplement that can prevent reproductive defects from zinc deficiency, and the bioavailability of zinc may be identical to zinc carbonate.

Animals↗

The fungicide benomyl (methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate) causes testicular dysfunction by inducing the sloughing of germ cells and occlusion of efferent ductules.

Adult male Sprague-Dawley rats (100 days of age) were given single oral doses of the fungicide benomyl (methyl 1-(butylcarbamoyl)-2- benzimidazolecarbamate) in dosages ranging from 25 to 800 mg/kg body weight. The testis and excurrent ducts were examined at 2 and 70 days posttreatment to determine the chemical effects on spermatogenesis and the epididymis. Primary effects seen at 2 days postexposure were testicular swelling and occlusions of the efferent ductules. Mean testis weight peaked with 400 mg/kg. Premature release of germ cells (sloughing), detected even with the lowest dosage (25 mg/kg), was the most sensitive short-term response to benomyl. Sloughing was found primarily in Stage VII of the spermatogenic cycle at the lower dosages, but at higher dosages sloughing extended into all stages except for Stages VIII-XI. Occlusions of the efferent ductules of the testis were dose-dependent and correlated with testis weight. Sperm and sloughed germ cells were compacted in the ductal lumen of occluded ductules, which were surrounded by two to four layers of polymorphonuclear leukocytes and other inflammatory cells. Although the caput epididymidis contained sloughed germ cells and appeared swollen, evidence of permanent occlusion was not found. The long-term (70 days) effects of benomyl were decreased testis weight (at 400 mg/kg), dose-dependent increases in seminiferous tubular atrophy, and increases in the number of reproductive tracts containing occluded efferent ductules. Fibrosis, granulomas, and abnormal growth were long-term consequences of occluded ductules, which were present 100% of the time in testes containing 26-100% seminiferous tubular atrophy. Only a few testes were found to be completely regressed. Occlusion of efferent ductules and disruption of the seminiferous epithelium by sloughing of germ cells are overlapping dose-dependent mechanisms responsible for short- and long-term effects of benomyl on the rat testis.

Animals↗

Sperm production in boars after nine generations of selection for increased weight of testis.

Body, testis, and epididymis weights were recorded and homogenization-resistant sperm nuclei were counted to determine daily sperm production and the number of sperm stored within the cauda epididymis (CAUDASP) in 145 boars of a control line (C) and 128 boars of a line selected for increased predicted weight of testis (TS) at 150 d of age. Random samples of boars were evaluated at five ages between 70 and 450 d in Generation 8 and 15 ages between 70 and 296 d in Generation 9. Data were analyzed using an animal model that included the fixed effect of line and the linear, quadratic, and cubic effects of age. Variance components were estimated using a DFREML algorithm. Boars of the TS and C line did not differ in body weight (P > .05) in Generation 8. In Generation 9, boars of line TS were heavier between 118 and 198 d of age (P < .001); thereafter, body weights of the lines were similar (P > .05). The increase in organ weights for the testes and epididymides between 70 and 160 d of age were greater (P < .01) for boars of line TS in each generation, and differences between the lines in testis weights established around puberty were maintained at 450 d of age. Daily sperm production and CAUDASP increased more rapidly at younger ages and plateaued at greater values (P < .05) in boars of line TS. At ages less than 200 d, boars of line TS produced more sperm per gram of parenchyma than control boars.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Removal of the olfactory bulbs delays photic reentrainment of circadian activity rhythms and modifies the reproductive axis in male Octodon degus.

The diurnal rodent, Octodon degus, exhibits robust sex differences in several circadian measures, including circadian period (tau) and reentrainment rates to photic and nonphotic (social) zeitgebers. The neural substrates underlying such physiological differences remain unknown. In female degus, olfactory bulbectomies (BX) inhibit socially-facilitated reentrainment, but do not alter photic reentrainment, entrained measures, or tau in constant darkness (DD). This experiment investigated the effects of BX in male degus on (i) photic reentrainment rates of circadian rhythms following a 6-h phase advance of the light-dark (LD) cycle; (ii) photic entrainment; (iii) tau of free-running activity rhythms in DD; and (iv) body weight, paired testis weight, and the reproductive hormones, testosterone, androstenedione and follicle stimulating hormone (FSH). BX significantly delayed photic reentrainment rates. They did not, however, modify tau, the phase of activity onset or offset, amplitude or duration (alpha) of the activity rhythm, mean daily locomotor activity levels, or body weight. FSH, testosterone and androstenedione were unaffected by BX, whereas paired testis weights were significantly greater in BX degus compared with shams. Thus, the olfactory bulbs influence photic reentrainment of circadian rhythms and modestly affect the reproductive axis in male degus. Our results suggest that the olfactory bulbs may be a neural source of observed sex differences in photic reentrainment in degus, and highlight interspecies variation in the olfactory bulbs' effects on entrained and free-running circadian rhythms and on reproduction.

Animals↗

Effects of the fungicide methyl-benzimidazol-2-yl carbamate (MBC) on mouse germ cells as determined by flow cytometry.

Dual-parameter (DNA, RNA) flow cytometry (FCM) measurements were made on testicular and epididymal sperm cells isolated from mice exposed by oral gavage to 0, 250, 500, or 1000 mg/kg X 5 d of the fungicide methylbenzimidazol-2-yl carbamate (MBC), which is known to bind with tubulin subunits and inhibit polymerization and microtubule formation. Effects of exposure to MBC were measured at 7, 24, and 39 d posttreatment. MBC had no effect on body weights, but testis weights and sperm parameters were altered, with few exceptions, only at the highest exposure level. Testis weights were reduced by about 25% at 7 and 24 d after exposure; recovery was observed by 39 d after treatment. FCM measurements of testicular cells showed relative percentages of certain testicular populations (round, elongating, and elongated spermatids) were different from the control pattern 7 and 24 d after treatment. The mean percent of cauda epididymal sperm head morphology abnormalities and the susceptibility of the nuclear DNA to denaturation were both elevated at 7, 24, and 39 d after exposure to 1000 mg/kg. The level of denaturation was determined by FCM measurements of the metachromatic shift in acridine orange (AO) stained sperm nuclei from green (native DNA) to red (single-stranded DNA) fluorescence and quantitated by the expression alpha t[red/(red + green] fluorescence. These data demonstrate that spermatogenesis is sensitive to high-dose MBC exposure resulting in an altered ratio of testicular cell types present, abnormal sperm head morphology, and an altered sperm chromatin structure.

Administration, Oral↗

A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development.

Nutrient restriction during pregnancy and lactation impairs growth and development. Recent studies demonstrate long-term programming of function of specific organ systems resulting from suboptimal environments during fetal life and development up to weaning. We determined effects of maternal protein restriction (50% control protein intake) during fetal development and/or lactation in rats on the reproductive system of male progeny. Rats were fed either a control 20% casein diet (C) or a restricted diet (R) of 10% casein during pregnancy. After delivery mothers received either C or R diet until weaning to provide four groups: CC, RR, CR and RC. We report findings in male offspring only. Maternal protein restriction increased maternal serum corticosterone, oestradiol and testosterone (T) concentrations at 19 days gestation. Pup birth weight was unchanged but ano-genital distance was increased by maternal protein restriction (P < 0.05). Testicular descent was delayed 4.4 days in RR, 2.1 days in CR and 2.2 days in RC and was not related to body weight. Body weight and testis weight were reduced in RR and CR groups at all ages with the exception of CR testis weight at 270 days postnatal age (PN). At 70 days PN luteinizing hormone and T concentrations were reduced in RR, CR and RC. mRNA for P450 side chain cleavage (P450scc) was reduced in RR and CR at 21 days PN but was unchanged at 70 days PN. Fertility rate was reduced at 270 days PN in RC and sperm count in RR and RC. We conclude that maternal protein delays sexual maturation in male rats and that some effects only emerge in later life.

Animals↗

Effects of ethanol consumption on the morphology of the rat seminiferous epithelium.

The effects of ethanol consumption on the morphology of the seminiferous epithelium, with particular emphasis on Sertoli cell ultrastructure, were examined during and following pubertal development. Sprague-Dawley rats were maintained on chronically high levels of ethanol for 7 weeks beginning at 29 days of age. Animals in Group 1 were fed a liquid diet containing ethanol (36% ethanol-derived calories) ad libitum. Group 2 animals were paired with animals in Group 1 and fed a liquid control diet in the amount consumed by their ethanol partners (g/kg body wt/day). Animals in Group 3 were fed Purina rodent chow ad libitum. Blood samples were collected at 60 days for determination of plasma testosterone levels. On day 79, each epididymis, the adrenals and the right testis were removed from anesthetized animals and weighed; the left testis was removed and processed for light and electron microscopy. Blood alcohol levels were consistently high throughout the feeding period, averaging 272.6 +/- 9.7 mg/100 ml at 1900 hours (1 hour after lights off) and 178.8 +/- 20.8 mg/100 ml at 1330 hours. Testosterone levels were lower in ethanol-consuming animals than in pair-fed or control subjects. Testis weight was also somewhat reduced in ethanol-consuming animals; however, when adjusted for body weight, relative testis weights were found to be increased in ethanol and pair-fed animals. Epididymal weights were reduced in both ethanol and pair-fed animals. Relative adrenal weights were increased by ethanol. The most dramatic effect of ethanol consumption was on the morphology of the seminiferous tubules.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Functional role of inducible nitric oxide synthase in the induction of male germ cell apoptosis, regulation of sperm number, and determination of testes size: evidence from null mutant mice.

Inducible nitric oxide synthase (iNOS) through its product, nitric oxide (NO), may contribute to the induction of germ cell apoptosis. Using adult iNOS-deficient mice, we characterized the reproductive hormonal profile and the testicular phenotype. Although there was no difference in body weight, mean testis weights in mutant mice were 30.77% higher, and testicular sperm count was 65.51% higher than control animals. No significant differences were apparent in plasma LH, FSH, and testosterone levels between these mice. Compared with wild-type mice, histomorphometric analysis showed that the mutant mice had a 39.63% increase in the number of pachytene spermatocytes and 33.79% in round spermatids, with no apparent changes in the number of preleptotene spermatocytes and spermatogonia. The incidence of spontaneous germ cell apoptosis detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay was lower at stages I-IV and XI-XII of iNOS-mutant mice compared with wild-type animals. The rate of germ cell proliferation estimated by quantitative assessment of the bromodeoxyuridine labeled preleptotene spermatocytes showed no significant change between wild-type and iNOS-deficient mice. When applying testicular warming (43 C for 15 min) to mice, the rate of germ cell apoptosis was elevated predominantly at early (I-IV) and late (XI-XII) stages, and less during stages V-VI, VII-VIII, and IX-X at 2 and 6 h after heat exposure in the wild-type mice. In contrast, the rate of apoptosis in mutant mice was markedly decreased at early and late stages 2 and 6 h after heat exposure. Pachytene spermatocytes and early round spermatids were most susceptible to heat-induced apoptosis in both mutant and control animals. Our studies demonstrate that: 1) deficiency of iNOS results in failure to eliminate a small portion of pachytene spermatocytes and round spermatids by apoptosis, resulting in a remarkable increase in testis weight and sperm output; 2) deficiency of iNOS confers partial resistance to heat-induced germ cell apoptosis. These experiments suggest that iNOS plays a physiological role in regulation of germ cell number and in determining testicular size.

Animals↗

Testosterone dose-dependency of sexual and nonsexual behaviors in the gonadotropin-releasing hormone antagonist-treated male rat.

The testosterone dose-dependency of several mating and nonmating behaviors was examined in the male rat, chemically castrated with a GnRH antagonist analog. Graded doses of testosterone enanthate (TE) were given to male rats to reinstate behaviors abolished by GnRH antagonist treatment. GnRH antagonist treatment alone markedly lowered serum LH, FSH and T concentrations and ventral prostate and testis weights. Open field behaviors were not significantly affected by GnRH antagonist treatment or castration. Scent-marking behavior was markedly suppressed by both castration and GnRH antagonist and restored by the lowest dose of TE (0.05 mg). All measures of male sexual behavior were impaired by GnRH antagonist treatment and castration and restored by the lowest dose of TE (0.05 mg). The doses of TE required to restore normal ventral prostate weights and testis weights were higher than those required to maintain scent marking and mating behaviors. No direct behavioral effects of the GnRH antagonist, other than those that can be explained by GnRH antagonist-induced suppression of testosterone were observed. The finding that sexual and nonsexual behaviors in the male rat have different testosterone requirements from those maintaining spermatogenesis and fertility may have significant implications for contraception.

Animals↗

A recombinant protein LHRH-PE40 for tumour therapy: preclinical safety studies.

LHRH-PE40, a recombinant DNA-derived protein composed of LHRH and Pseudomonas aeruginosa exotoxin A, is being developed for the treatment of malignant tumours. This experiment was designed to assess its preclinical safety. Reproductive toxicity studies, pharmacokinetic studies, single- and repeat-dose intraperitoneal or intravenous toxicity studies in mice, rats and monkeys were conducted to assess the toxicity of LHRH-PE40. In intravenous single-dose studies in mice, the LD50 was 731.26 microg/kg and 676.03 microg/kg in male and female mice respectively. In single-dose studies and repeat-dose range-finding studies in rats, dose-limited severe vascular leakage syndromes occurred. In repeat-dose long-term studies, except drug-related vascular leakage syndromes, other drug-related changes included decreased testis weight and testis atrophy. In single-dose and repeat-dose studies in monkeys, dose-limited acute tubular necrosis of the kidneys was the chief finding. In reproductive studies, drug-related changes were decreased food intakes, decreased testis weight and uterus weight, decreased foetus weight and increased foetus mortality, increased maternal and F1 offspring mortality and decreased maternal and F1 offspring body weight. Pharmacokinetic studies showed a similar half-time of distribution and clearance in mice and monkeys. Tissue distribution showed a high concentration in the kidneys and a low concentration in the brain. LHRH-PE40 induced vascular leak syndromes in rats and acute tubular necrosis in monkeys. It also led to testicle atrophy in rats and overt productive toxicity to parents and F1 generations in mice. Because of these findings, it should be monitored carefully in human clinical trials for things such as respiratory, urinary and reproductive toxicities.

ADP Ribose Transferases↗

Effects of unilateral castration and unilateral cryptorchidism of the Holstein bull on plasma gonadotropins, testosterone and testis anatomy.

The effects of unilateral castration (UC) and induced unilateral cryptorchidism (CR) on plasma hormones and testis anatomy were studied in 36 Holstein bulls altered at either 3, 6 or 9 mo of age (n = 12). Plasma hormone concentrations were determined in six samples collected at hourly intervals on d 0, 1, 3, 7, 14 and 30, and then at monthly intervals through 6 mo after gonadal manipulation. Although plasma testosterone (T) showed a transient decrease (P less than .05) immediately after treatment, mean plasma concentrations of luteinizing hormone (LH) and T were unaffected by UC or CR over the 6-mo period (P greater than .05). Both hormones increased (P less than .05) in concentration with advancing age. Plasma follicle stimulating hormone (FSH) concentration was greater (P less than .05) in UC than in intact (IN) bulls overall, while FSH in CR bulls did not differ (P greater than .05) from either group. At slaughter, 11 mo after gonadal alteration, mean testis weight, ratio of testis weight to body weight and mean testis sperm cell numbers were increased (P less than .05) in UC bulls compared with mean testis values in intact (IN) bulls. Unilateral castration increased (P less than .05) seminiferous tubuler diameter and seminiferous epithelial cell height from basement membrane to the border of the lumen, but did not alter the ratio of tubuler to interstitial space within the testis. Seminiferous tubuler diameter and epithelial cell height were increased (P less than .05) in CR compared with IN bulls. Unilateral gonadal alteration at 3 mo of age caused a greater (P less than .05) hypertrophy of the scrotal testis in both UC and CR bulls than alteration at 6 or 9 mo of age. Results indicate that unilateral gonadal disruption is followed by rapid compensation in testis T production, little change in systemic LH and a rapid increase in secretion of FSH in the bull within those ages investigated. Further, UC elicits a greater compensatory hypertrophy than CR and the pituitary-testis endocrine axis is more responsive to alteration at 3 mo than at 6 or 9 mo of age in the bull.

Animals↗

Neonatal polychlorinated biphenyl treatment increases adult testis size and sperm production in the rat.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants which decrease serum thyroxine (T4) concentrations. We have previously demonstrated that neonatal hypothyroidism in the rat increases Sertoli cell numbers, adult testis weight, and daily sperm production (DSP). The aim of this study was to determine if neonatal PCB treatment increases adult testis weight and DSP. Treated rats received either Aroclor 1242 or 1254 (0.4-3.2 mg/day), from birth to Day 25 by daily injection; some treated litters also received T4 replacement. Controls received vehicle alone. Tritiated thymidine autoradiography was used to assess Sertoli cell proliferation in 15-day control and Aroclor-treated rats. Serum T4 was measured at 25, 45, and 135 days of age, and serum testosterone, testis weight, DSP, and testicular histology were examined at 135 days. Both Aroclor 1242 and 1254 suppressed serum T4 concentrations; Aroclor 1254 was more potent and long lasting. Testis weight was increased 22 and 13% in rats that received the 1.6 and 3.2 mg/day Aroclor 1242 doses, respectively, while the 0.4 mg/day dose did not produce significant increases. Aroclor 1254 produced significant increases in testis weight of 13 and 23% at the 0.4 and 1.6 mg/day doses, respectively. The 1.6 mg/day Aroclor 1242 and the 0.4 and 1.6 mg/day Aroclor 1254 doses increased DSP by 27, 11, and 42%, respectively; other treatments did not produce significant increases. At 15 days of age, Sertoli cell proliferation was greater in treated rats than in controls. T4 replacement decreased or eliminated the increased testis weight and DSP seen in Aroclor-treated rats. The highest dose of Aroclor 1242 and both doses of Aroclor 1254 decreased adult body weight, while other treatments did not. These results indicate that neonatal PCB treatment increases adult testis weight and DSP in rats. PCBs produce this effect primarily by inducing hypothyroidism, which leads to increased Sertoli cell proliferation, testis weight, and DSP. Thus PCBs, despite inhibitory effects on adult reproductive organs, can paradoxically stimulate increases in adult testis weight and DSP when administered neonatally. These data emphasize the pleiotropic nature of PCB effects and the susceptibility of the developing reproductive system to environmental factors.

Animals↗