Effects of subchronic ifosfamide-mesna treatment on testes and semen characteristics in the rabbit

Ifosfamide, a chemotherapeutic agent with a broad spectrum of antineoplastic activity, is concurrently administered with the uroprotectant mesna to avoid the urotoxic effect. This study was undertaken to investigate possible effects of ifosfamide-mesna treatment on the testes and semen characteristics in rabbits. Sexually mature New Zealand White male rabbits received intravenously 10 weekly treatments of ifosfamide+mesna (groups A, B and C received 30, 45 or 60 mg/kg of body weight ifosfamide+6, 9 or 12 mg/kg of body weight mesna, respectively, followed by a second equal dose of mesna 4 h later); groups MA, MB and MC received mesna alone at corresponding doses; and group S received normal saline. Reproductive organ weight as well as various qualitative and quantitative parameters of testis histology (minor diameter of seminiferous tubules, the most advanced germ cell type in seminiferous tubule identified in cross sections, and the number of germ cells per stage 1 seminiferous tubule cross section) were determined 1 day and 20 weeks after the treatment period, while semen quality (sperm count, sperm morphology and sperm progressive motility) and libido were evaluated on a weekly basis. Changes were noted only in the ifosfamide+mesna treated animals. One day after treatment, reproductive organ weights were decreased in groups A–C. Major histopathological lesions were not found; however, quantitative histological endpoints were altered in groups A–C. Transient oligospermia and teratozoospermia were noted in groups B and C, while asthenozoospermia was observed in group C only. The time course of these sperm alterations suggested possible bioaccumulation and residual activity of ifosfamide. Libido remained normal. The decrease in reproductive organ weights persisted in groups B and C to 20 weeks after treatment but only one quantitative histological endpoint, the number of the round spermatids per stage 1 seminiferous tubule cross section, remained decreased in group C. These results suggest that subchronic treatment with ifosfamide-mesna suppressed spermatogenesis and epididymal sperm maturation in the rabbit. Germinal epithelium recovery was not complete because although sperm characteristics returned to pretreatment values, not all histological alterations were ameliorated.     

Reproductive effects of endosulfan on male offspring of rats exposed during pregnancy and lactation.

1. The reproductive effects of endosulfan on the male offspring of rats were examined. Dams were treated orally with 0, 1.5 or 3.0 mg endosulfan/kg from day 15 of pregnancy to postnatal day (PND) 21 of lactation. The male offspring rats were investigated at PND 65 or 140, corresponding to the pubertal and adulthood stage of development. 2. The dose of 3.0 mg endosulfan/kg induced a decrease in maternal body weight during pregnancy, but litter size and mean birth weight were not affected. Similarly, the age at testis descent and preputial separation was not affected on the male offspring. 3. The daily sperm production (x10(6)) was permanently decreased in the highest dose group when investigated at puberty and at adulthood. At the lowest dose, however, the daily sperm production was significantly reduced only at puberty. 4. Histologically, the percentage of seminiferous tubules showing complete spermatogenesis was significantly decreased at puberty. This finding may explain the decrease in daily sperm production observed in the endosulfan-exposed male rats. 5. The results of this study show that low doses of endosulfan have no apparent effect on developmental landmarks or on the weight of reproductive and accessory sex organ. Daily sperm production was the most susceptible endpoint in the male offspring exposed to endosulfan during pregnancy and lactation. To further understand the reproductive effects of endosulfan on male rat offspring, additional reproductive and toxicokinetic studies should be carried out to determine the extent of endosulfan exposure in male rat offspring in utero and during lactation.     

Reproductive toxicity of 2,4-toluenediamine in the rat. 3. Effects on androgen-binding protein levels, selected seminiferous tubule characteristics, and spermatogenesis

In previous studies we demonstrated reduced fertility, arrested spermatogenesis, and diminished circulating testosterone levels in rats fed 0.03% 2,4-toluenediamine (TDA) for 10 wk. These studies were extended in three experiments by determining TDA effects on androgen-binding protein (rABP) production and on seminiferous tubule structure, and on early changes in testes morphology and spermatogenesis. In the first experiment, rats fed 0.03% TDA for 10 wk showed a 7- to 9-fold increase in rABP content in testicular cytosol or in media of cultured seminiferous tubules, a 4-fold increase in serum rABP, but a two-thirds decrease in epididymal rABP levels. Testes examination by transmission electron microscopy revealed degenerative changes in Sertoli cells with, where present, normal spermatocytes and spermatids. In the second experiment, 0.03% TDA fed for 4, 6, or 8 wk resulted in a doubling of testes/body weight ratios and a highly correlated 2.5- to 2.9-fold increase in seminiferous tubule fluid volume. An approximately 50% decrease in epididymal sperm reserves was found after 6 or 8 wk of TDA exposure. After 10 wk of exposure to 0.03% TDA, testicular weight was the same as in control-fed rats but seminiferous tubule fluid volume was still elevated. These changes in testicular characteristics indicate TDA effects on Sertoli cell function, on RABP release from the testes (and epididymides), and possibly on tubular fluid transport. In the third experiment, rats fed 0.06% TDA for 1 wk showed a 25% decrease in epididymal sperm content, reduced epididymal weight, and minor structural changes in Sertoli cells. After 3 wk of 0.06% TDA feeding, sperm counts were further reduced, and were accompanied by a dramatic increase in testes weight, intense fluid accumulation, and ultrastructural changes in Sertoli cells. No significant changes in serum testosterone levels were noted in the TDA-treated rats. The results of this third experiment demonstrate TDA toxicity on testicular spermatogenesis within 3 wk of TDA feeding. The within 3 wk of TDA feeding. The findings in this study suggest that the early inhibition of spermatogenesis by TDA is mediated through Sertoli cell damage.     

Quercetin attenuates lambda cyhalothrin‐induced reproductive toxicity in male rats

The aim of this study was to evaluate the possible protective effects of Quercetin (Qe) against oxidative stress induced by λ cyhalothrin (LTC) in reproductive system. Thirty‐two male rats were divided into four groups. First group was allocated as the control group. Second group was given a Qe alone while the third group received a LTC alone. Animals in the fourth group were given a Qe with LTC. Caudae epididymis was removed for sperm analysis. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione‐S‐transferase (GST), and reduced glutathione (GSH) were determined in the testis. Additionally, the different histopathologic changes were observed in the testis of animals. LTC exposure significantly increased the abnormal morphology and LPO. On the contrary, sperm motility, viability and count, levels of GSH, and activities of SOD, CAT, GPx, and GST were significantly decreased compared to controls. Qe with LTC offset the decrease in functional sperm parameters, antioxidants enzymatic activities, and nonenzymatic antioxidant levels when compared with LTC‐treated rats. Furthermore, LTC showed irregular seminiferous tubules containing only Sertoli cells and Qe with LTC caused regular seminiferous tubules showing spermatogenesis at level of spermatocytes. We conclude that LTC‐induced oxidative stress and functional sperm parameters in male rats, and dietary of Qe attenuates the reproductive toxicity of LTC to restore the antioxidant system and sperm parameters in male rats. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 673–680, 2013.     

Comparative metabolism of nitroaromatic compounds in freshwater,brackish water and marine decapod crustaceans

1. The metabolic pathways of p-nitroanisole, 4-nitro-m-cresol and methyl parathion in Malaysian prawns (Macrobrachium rosenbergii), ridgeback prawns (Sicyonia ingentis) and crayfish (Procambarus clarkii) were compared.

2. The Malaysian prawns and ridgeback prawns were shown to O-demethylate 29% and 11%, respectively, of an accumulated level of p-nitroanisole, while crayfish were able to O-demethylate 98% of the accumulated level of nitroanisole. 4-Nitro-m-cresol oxidation was not detected in either prawn species. In contrast, 5-hydroxy-2-nitrobenzaldehyde was the major metabolite formed from nitrocresol metabolism by crayfish.

3. Both prawn species readily dearylated methyl parathion to form p-nitrophenol and p-nitrophenyl conjugates. Crayfish displayed a similar trend in methyl parathion metabolism.

4. Nitroreduction was observed in the metabolism of 4-nitro-m-cresol by ridgeback prawns, which excreted 4-nitroso-m-cresol as a minor product. Reduction products were not observed in the metabolism of the three substrates by Malaysian prawns or crayfish.

5. Conjugation was overall the dominant detoxication pathway observed in the decapods. Malaysian prawns conjugated p-nitrophenol and 4-nitro-m-cresol to form the corresponding β-D-glucosides and sulphate monoesters. Ridgeback prawns formed β-D-glucosides in small quantities, preferring conjugation of p-nitrophenol and 4-nitro-m-cresol to form sulphates and unknown conjugates through a unique conjugation pathway. Crayfish conjugated the phenolic substrates to form exclusively the β-glucosides.

6. The unknown conjugates formed by ridgeback prawns had chromatographic properties similar to the corresponding β-D-glucosides but were refractory to the deconjugation by α- or β-glucosidase, β-galactosidase, aryl sulphatase and β-glucuronidase. Phenolic conjugation ability appeared to follow the order of ridgeback prawns > Malaysian prawns > crayfish.     

Silver nanoparticles effects on epididymal sperm in rats

The motivation of our study was to examine the acute effects of intravenously administered a single bolus dose of silver nanoparticles (AgNPs) on rat spermatogenesis and seminiferous tubules morphology. In the treated rats compared to the vehicle treated control animals, the experiments revealed a size-dependent (20 nm and 200 nm), dose-dependent (5 and 10 mg/kg body mass) and time-dependent (24 h, 7 and 28 days) decrease the epididymal sperm count measured by histological methods. In parallel AgNPs injection increased the level of DNA damage in germ cells, as measured by alkaline comet assay. Histological examination of the testes showed change in the testes seminiferous tubule morphometry in 200 nm Ag NPs treated rats. No change of body weight, adipose tissue distribution and the frequency of abnormal spermatozoa was observed. Twenty nanometers AgNP appeared to be more toxic than 200 nm ones.     

杨梅黄酮对铅染毒雄性小鼠生精功能及激素水平的影响#br#

目的 研究杨梅黄酮（myricetin）对铅染毒所致雄性小鼠生精障碍的影响,并探讨其作用机制。方法 选 取昆明种小鼠60只,随机分成对照组、染铅组、甲睾酮组（10 mg/kg,即阳性对照组）及杨梅黄酮低、中、高剂量组,每组 10只,除对照组外,其他5组采用腹腔注射醋酸铅（20 mg/kg,7 d）建立雄性小鼠生精障碍模型,造模第2天始,杨梅黄 酮低、中、高剂量组分别灌胃杨梅黄酮 100、200、400 mg/kg,连续 42 d。观察雄性小鼠的睾丸指数、精子密度、精子畸 形率变化,检测血清中睾酮（T）、卵泡刺激素（FSH）、黄体生成素（LH）及睾丸组织中的山梨醇脱氢酶（SDH）、丙二醛 （MDA）水平的变化,HE染色观察睾丸组织的病理改变。结果 与染铅组比较,杨梅黄酮各剂量组的精子密度增高、 睾丸指数增大、精子畸形率降低,杨梅黄酮各剂量组血清LH、FSH含量降低,T升高,睾丸组织中MDA含量降低、SDH 活性增高（P＜0.05）。睾丸组织镜下可见染铅组生精上皮变薄,生精细胞层次和数量减少,生精小管腔见少量精子形 成,而杨梅黄酮中、高剂量可改善醋酸铅所致的睾丸组织改变。结论 杨梅黄酮可通过抗氧化作用、减轻醋酸铅所 致睾丸组织氧化应激损伤,促进睾酮的分泌,提高睾丸及精子活性,从而改善睾丸的生精功能。     

Prenatal Exposure to Diesel Exhaust Impairs Mouse Spermatogenesis

The effect of prenatal exposure to diesel exhaust (DE) was investigated. Twenty pregnant ICR mice were exposed to DE at the particle concentration of 1.0 mg/m³, from d 2 until d 16 postcoitum. Male offspring were kept alive until 12 wk of age, and then male reproductive organ weight, daily sperm production (DSP), serum testosterone level, and mRNA expression of sex steroid hormone synthesis process-related factors were measured. Serum testosterone levels of the exposed group were reduced significantly at 3 wk, whereas they were elevated significantly at 12 wk. DSP was also markedly reduced at 5 and 12 wk. Histological examination showed multinucleated giant cells in the seminiferous tubules of the exposed group as well as partial vacuolation of the seminiferous tubules. Follicle-stimulating hormone receptor (FSHR) mRNA expression and steroidogenesis acute regulatory (StAR) protein were significantly increased at 5 wk and 12 wk, respectively. This study suggests that prenatal exposure to DE has detrimental effects on mouse spermatogenesis in offspring.     

Effects of abamectin exposure on male fertility in rats: potential role of oxidative stress-mediated poly(ADP-ribose) polymerase (PARP) activation

Despite the known adverse effects of abamectin pesticide, little is known about its action on male fertility. To explore the effects of exposure to abamectin on male fertility and its mechanism, low (1 mg/kg/day) and high dose (4 mg/kg/day) abamectin were applied to male rats by oral gavage for 1 week and for 6 weeks. Weight of testes, serum reproductive hormone levels, sperm dynamics and histopathology of testes were used to evaluate the reproductive efficiency of abamectin-exposed rats. Abamectin level was determined at high concentrations in plasma and testicular tissues of male rats exposed to this pesticide. The testes weights of animals and serum testosterone concentrations did not show any significant changes after abamectin exposure. Abamectin administration was associated with decreased sperm count and motility and increased seminiferous tubule damage. In addition, significant elevations in the 4-hydroxy-2-nonenal (4-HNE)-modified proteins and poly(ADP-ribose) (PAR) expression, as markers for oxidative stress and poly(ADP-ribose) polymerase (PARP) activation, were observed in testes of rats exposed to abamectin. These results showed that abamectin exposure induces testicular damage and affects sperm dynamics. Oxidative stress-mediated PARP activation might be one of the possible mechanism(s) underlying testicular damage induced by abamectin.     

Perinatal exposure to low doses of tributyltin chloride reduces sperm count and quality in mice

Exposure to endocrine disruptors (EDs) during early development might lead to adverse health outcomes later in life. Tributyltin (TBT), a proven ED, is widely used in consumer goods and industrial products. Herein we demonstrate the effects of low doses of tributyltin chloride (TBTCl) on reproduction of male KM mice. Pregnant mice were administered by gavage with 0, 1, 10, or 100 μg TBTCl/kg body weight/day from day 6 of pregnancy through the period of lactation. TBTCl dramatically decreased sperm counts and motility on postnatal days (PNDs) 49 and 152. Meanwhile, a significant increase in sperm abnormality was observed in exposed mice on PND 49, but comparable to that in the control on PND 152. The histopathological analysis of testes of treated animals showed a dose‐dependent increase in sloughing of germ cells in seminiferous tubules. Mice treated with 10 μg TBTCl/kg exhibited decreased intratesticular 17β‐estradiol (E2) levels on PND 49, and then followed by an obvious recovery on PND 152. While, no significant differences in serum E2, testosterone (T) levels and intratesticular T levels were detectable between control and TBTCl‐exposed offspring at the sacrifice. These results suggest that perinatal TBTCl exposure is implicated in causing long lasting alterations in male reproductive system and these changes may persist far into adulthood. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 44–52, 2015.     

In Utero Exposure to Diethylstilboestrol or 4‐n‐Nonylphenol in Rats: Number of Sertoli Cells,Diameter and Length of Seminiferous Tubules Estimated by Stereological Methods

Abstract: The effects on testis weight and histopathology were studied in 11‐day‐old male Wistar rats after prenatal exposure to peanut oil (control), diethylstilboestrol 30 μg/kg b.wt./day, or 4‐n‐nonylphenol 75 mg/kg b.wt./day from gestational day 11 to 18. Additionally, the diameter and length of seminiferous tubules, and the number of Sertoli cells were investigated with stereological methods. Such unbiased methods have not previously been applied on testis diameter and length or on Sertoli cell number of 11‐day‐old rats. In the control group, the mean length of the seminiferous tubule was 3.0 m±0.6, the mean diameter of the seminiferous tubule was 83 μm±6, and the mean number of Sertoli cells was 26.1×10⁶±4.6. No differences in testis weight, histopathology, or length or diameter of the seminiferous tubules were observed in the diethylstilboestrol and nonylphenol exposed groups when compared to the control group. In the diethylstilboestrol‐treated group, a statistically significant decrease in the number of Sertoli cells was observed (P<0.01) when compared to the control group, whereas nonylphenol had no effect. The result suggests that diethylstilboestrol decreases Sertoli cell proliferation in the foetal testis and furthermore indicate that oestrogens may pose a risk to the reproductive capacity in sensitive species, including man.     

Prenatal exposure to diesel exhaust impairs mouse spermatogenesis

The effect of prenatal exposure to diesel exhaust (DE) was investigated. Twenty pregnant ICR mice were exposed to DE at the particle concentration of 1.0 mg/m3, from d 2 until d 16 postcoitum. Male offspring were kept alive until 12 wk of age, and then male reproductive organ weight, daily sperm production (DSP), serum testosterone level, and mRNA expression of sex steroid hormone synthesis process-related factors were measured. Serum testosterone levels of the exposed group were reduced significantly at 3 wk, whereas they were elevated significantly at 12 wk. DSP was also markedly reduced at 5 and 12 wk. Histological examination showed multinucleated giant cells in the seminiferous tubules of the exposed group as well as partial vacuolation of the seminiferous tubules. Follicle-stimulating hormone receptor (FSHR) mRNA expression and steroidogenesis acute regulatory (StAR) protein were significantly increased at 5 wk and 12 wk, respectively. This study suggests that prenatal exposure to DE has detrimental effects on mouse spermatogenesis in offspring.     

Toxic effects of cypermethrin on the male reproductive system: with emphasis on the androgen receptor

The 15‐day intact adult male assay was used to investigate the reproductive toxicity of cypermethrin. We also evaluated the contributions of the androgen receptor (AR) to cypermethrin‐induced reproductive impairments. Sixty adult male Sprague–Dawley rats were randomly divided into five groups and treated with different doses of cypermethrin (0, 6.25, 12.5, 25 and 50 mg kg^?1 per day) by oral gavage for 15 days. After the rats were sacrificed, the testes, epididymides, seminal vesicles and prostates were excised and weighed. One testis was frozen to be used for daily sperm production. Another testis was processed for AR immunohistochemical analysis and electron microscopic observation. We found that the weights of prostates were significantly decreased in cypermethrin treatment at doses of 25 and 50 mg kg^?1 per day. Rats treated with cypermethrin at 50 mg kg^?1 per day exhibited a significant reduction in testicular daily sperm production. Seminiferous tubule changes were noted, including atrophy and distorted seminiferous tubules, reduction and deformation of spermatogonia, spermatocyte and disordered arrangement of spermatoblasts. Ultrastructural changes were found in cypermethrin‐treated groups with disrupted cellular junctions, abnormal morphology of the nucleus, necrosis of spermatogonia spermatocytes and Sertoli cells. To clarify the possible mechanism, AR expression and the serum levels of testosterone were assayed. AR levels were significantly reduced in the rats treated with cypermethrin and the serum levels of testosterone were reduced in cypermethrin treatment at a dose of 50 mg kg^?1 per day. These data suggested that cypermethrin can induce impairments of the structure of seminiferous tubules and spermatogenesis in the male rats. The impairments can be attributed to the reduced AR expression. Copyright © 2011 John Wiley & Sons, Ltd.     

Microdose vasal injection of sodium fluoride in the rat

A single microdose (50 micrograms/50 microL) injection of sodium fluoride (NaF) into the vasa deferentia of adult male albino rats (Rattus norvegicus) caused arrest of spermatogenesis and absence of spermatozoa in the lumina of the seminiferous tubules of the testes, which consequently led to a decline in the sperm count in the caudae epididymides. Scanning electron microscopy of cauda and vas deferens sperm revealed deflagellation and tail abnormalities. This is probably related to the alterations in the internal milieu of these organs which rendered the spermatozoa immotile and consequently caused fertility impairment in the experimental animals. Thus microdoses of sodium fluoride were found to affect reproductive function and fertility rate.     

Vitamin E-supplementation protect chromium (VI)-induced spermatogenic and steroidogenic disorders in testicular tissues of rats

Excess chromium (Cr) exposure is associated with various pathological conditions including reproductive dysfunction. Generation of oxidative stress is one of the plausible mechanisms behind Cr induced cellular deteriorations. The efficacy of vitamin E to combat Cr induced oxidative damage in adult rat testis has investigated in the current study. Adult male rats exposed to hexavalent Cr (intraperitoneal injection with 0.4 mg K₂Cr₂O₇/kg bw/day) for 26 days resulted in decreased accessory sex organs weight compared to controls. Development of oxidative stress in testis was evidenced by increased lipid peroxidation along with decreased superoxide dismutase (SOD) and catalase activities than control animals. Marked reduction in the activities of testicular steroidogenic enzymes; Δ⁵3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, serum testosterone and Leutinizing Hormone (LH) levels were observed. However significant increase in serum Follicle Stimulating Hormone (FSH) level was observed with Cr treated group. Histological evaluation of testis revealed degeneration of stage VII spermatogenic cycle along with decrease in epithelial cell height in epididymis and seminiferous tubules; number of different germ cells per seminiferous tubule and seminiferous tubular diameter reduced after Cr exposure. Simultaneous oral supplementation of vitamin E (50 mg/kg bw/day) in Cr exposed rats showed less oxidative damage and restored the otherwise altered testicular activities. Epididymal sperm number was also restored in vitamin E-supplemented group than Cr induced rats. This study implicates vitamin E as a possible protective agent against Cr induced spermatogenic and steroidogenic alteration.     

Effects of abamectin exposure on male fertility in rats: Potential role of oxidative stress-mediated poly(ADP-ribose) polymerase (PARP) activation

Despite the known adverse effects of abamectin pesticide, little is known about its action on male fertility. To explore the effects of exposure to abamectin on male fertility and its mechanism, low (1 mg/kg/day) and high dose (4 mg/kg/day) abamectin were applied to male rats by oral gavage for 1 week and for 6 weeks. Weight of testes, serum reproductive hormone levels, sperm dynamics and histopathology of testes were used to evaluate the reproductive efficiency of abamectin-exposed rats. Abamectin level was determined at high concentrations in plasma and testicular tissues of male rats exposed to this pesticide. The testes weights of animals and serum testosterone concentrations did not show any significant changes after abamectin exposure. Abamectin administration was associated with decreased sperm count and motility and increased seminiferous tubule damage. In addition, significant elevations in the 4-hydroxy-2-nonenal (4-HNE)-modified proteins and poly(ADP-ribose) (PAR) expression, as markers for oxidative stress and poly(ADP-ribose) polymerase (PARP) activation, were observed in testes of rats exposed to abamectin. These results showed that abamectin exposure induces testicular damage and affects sperm dynamics. Oxidative stress-mediated PARP activation might be one of the possible mechanism(s) underlying testicular damage induced by abamectin.     

Toxic effects of Microcystis cell extracts on the reproductive system of male mice

In this paper, the reproductive toxicity of male mice treated with Microcystis aeruginosa cell extracts containing microcystins was examined. In contrast to the control group, male mice exposed intraperitoneally to 3.33 or 6.67 μg microcystins/kg body weight for 14 days had decreased mean body weight, and the mean absolute weight of the testes and epididymides was decreased. However, the mean relative weight of the testes increased compared to the controls. In addition, histological examination of microcystin-treated mice indicated that the testes were damaged and the space between the seminiferous tubules was more pronounced compared to control mice. The quality of mature sperm in the seminiferous tubules was also decreased in treated mice compared with the control group. Further studies showed that motility and viability of the sperm from microcystin-treated mice were reduced, but no significant difference was found in the concentration and abnormality of the sperm from treated mice compared to the control. This study indicated that microcystins had numerous toxic effects on the reproductive system of male mice.     

Effects of polychlorinated biphenyls in CD-1 mice: reproductive toxicity and intergenerational transmission

Several studies indicate that in utero and perinatal exposure to polychlorinated biphenyls (PCBs) induces adverse reproductive effects, but it remains unclear whether such effects may be transmitted to subsequent generations. We therefore investigated the association between maternal exposure to PCBs and reproductive health in male and female offspring over three generations. Mouse dams were fed 0, 1, 10, and 100 μg/kg/day of a PCB mixture (101 + 118) during pregnancy and lactation. PCB levels were measured in the tissues of both dams and offspring. PCB concentrations at all doses investigated were greater in the offspring than in the dams (p ≤ 0.0001) confirming that the progeny were exposed as a result of maternal exposure. In F1 offspring, exposure to PCBs resulted in reductions in (1) testis weight (p ≤ 0.05) and seminiferous tubule diameter (p ≤ 0.05), (2) sperm viability (p ≤ 0.0001) and developmental capacity (p ≤ 0.05), (3) ovary weight (p ≤ 0.05), (4) oocyte developmental capacity (p ≤ 0.05), and (5) increased follicular atresia (p ≤ 0.0001). In females, adverse effects were observed only in the F1 animals. In contrast, male offspring exhibited reduced sperm viability and altered seminiferous tubule distribution up to the third generation, showing intergenerational transmission. In summary, our data indicate that exposure to PCBs at the time of gonadal sex determination perturbed, significantly, the reproductive physiology of male and female offspring in adulthood. Furthermore, male reproductive deficiencies may be observed in at least two further generations. These findings have significant implications for reproductive health and fertility of animals and humans.     

Reproductive toxicity of 1-bromopropane, a newly introduced alternative to ozone layer depleting solvents, in male rats.

1-Bromopropane has been newly introduced as an alternative to ozone-depleting solvents. We aimed to clarify its dose-dependent reproductive toxicity in male rats. Thirty-six Wistar male rats were randomly divided into 4 groups of 9. The groups were exposed to 200, 400, or 800 ppm 1-bromopropane or only fresh air, 8 h per day for 12 weeks. Epididymal sperm indices were evaluated after a 12-week exposure. The testes, epididymides, seminal vesicle, prostate, and other organs were weighed and examined histopathologically. Spermatogenic cells, in stage VII seminiferous tubules, and retained spermatids, at the basal region of stages IX-XI seminiferous epithelium, were counted. Plasma testosterone levels were measured by radioimmunoassay. The testicular weight did not significantly change, but the weight of epididymides, seminal vesicle, and prostate dose-dependently decreased. The weight of seminal vesicle decreased significantly at the lowest concentration of 200-ppm and over. 1-Bromopropane induced a dose-dependent decrease in the epididymal sperm count and in motility, as well as an increase in tailless sperm and sperm with an immature head shape. The spermatogonia, preleptotene spermatocytes, pachytene spermatocytes, and round spermatids did not decrease significantly at stage VII. Retained, elongated spermatids near the basement membrane at the postspermiation stages IX-XI increased dose-dependently. Plasma testosterone levels significantly decreased at the 800-ppm dosage. 1-Bromopropane caused failure of spermiation. Its reproductive toxicity is different from that of 2-bromopropane, which specifically impairs spermatogonia. Thus, this solvent may have serious reproductive toxic effects in men, and should be used very cautiously in the workplace.     

蒽贝素对雄性大鼠血浆性激素水平及附睾精子质量的影响

目的 研究蒽贝素对雄性大鼠血浆性腺激素水平、附睾精子质量、睾丸组织结构的影响,探讨蒽贝素降低雄性大鼠生育能力的作用机制。方法 给雄性性成熟大鼠sc蒽贝素铵盐溶液30 d,末次给药后2 h,测定血浆性激素水平;检查附睾精子质量;观察睾丸组织结构。结果 与对照组比较,给药30 d后,蒽贝素高、中剂量（40、20 mg/kg）组大鼠血浆睾酮、黄体生成素、卵泡刺激素水平、附睾精子活率、精子密度明显降低,组间差异有统计学意义（P＜0.05）,附睾精子畸形率和顶体完整率无明显变化,显微镜下见睾丸组织呈萎缩性病变,曲精细管扁平、塌陷,管内精母细胞减少,附睾精细管内精子稀少。结论 蒽贝素抑制丘脑-垂体-性腺轴活动,降低雄性大鼠血浆性激素水平,引起睾丸萎缩和附睾精子活率、精子密度降低,使雄性大鼠生育能力下降。