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.     

Detrimental effects of prenatal exposure to filtered diesel exhaust on mouse spermatogenesis

We recently showed that prenatal exposure to diesel exhaust (DE) disrupts spermatogenesis in mouse offspring. This study was undertaken to determine whether filtered DE in which 99.97% of diesel exhaust particles >0.3 μm in diameter were removed affects spermatogenesis in growing mice. After prenatal exposure to filtered DE for 2–16 days postcoitum, we examined daily sperm production (DSP), testicular histology, serum testosterone levels and mRNA expression of hormone synthesis process-related factors. In the filtered DE exposed group, DSP was markedly reduced at 12 weeks compared with the control group; clean air exposed group. Histological examination showed multinucleated giant cells and partial vacuolation in the seminiferous tubules of the exposed group. Testosterone was elevated significantly at 5 weeks. Moreover, luteinizing hormone receptor mRNA at 5 and 12 weeks, 17α-hydroxylase/C17-20-lyase and 17β-hydroxysteroid dehydrogenase mRNAs at 12 weeks were significantly elevated. These results suggest that filtered DE retains its toxic effects on the male reproductive system following prenatal exposure.     

Maternal fenvalerate exposure during pregnancy persistently impairs testicular development and spermatogenesis in male offspring

Fenvalerate, a widely used pyrethroid insecticide, has been associated with poor semen quality. As yet, little is known about the effects of prenatal fenvalerate exposure on testicular development. The present study investigated the effects of prenatal fenvalerate exposure on testicular development and spermatogenesis. The pregnant mice were administered fenvalerate (30 mg/kg) by gavage daily from gestational day (gd) 13 to gd 18. The weights of testes and epididymides were significantly decreased in mice whose mothers were exposed to fenvalerate during pregnancy. Importantly, maternal fenvalerate exposure during pregnancy markedly decreased the number of mature seminiferous tubules (stages VII and VIII) in testes of adult male offspring. In addition, maternal fenvalerate exposure during pregnancy significantly reduced the number of epididymal spermatozoa in adult male offspring. Additional experiments showed that the level of serum testosterone (T) was significantly decreased in male fetuses whose mothers were exposed to fenvalerate during pregnancy. Correspondingly, mRNA and protein levels of P450_17α, a T synthetic enzyme, were significantly decreased in fetal testes. Moreover, the disruptive effect of prenatal fenvalerate exposure on testicular T synthesis was irreversible. In conclusion, prenatal fenvalerate exposure irreversibly impairs testicular development and spermatogenesis at least into early adulthood.     

In Utero Exposure to Environmentally Relevant Concentrations of PCB 153 and PCB 118 Disrupts Fetal Testis Development in Sheep

Polychlorinated biphenyls (PCB) are environmental pollutants linked to adverse health effects including endocrine disruption and disturbance of reproductive development. This study aimed to determine whether exposure of pregnant sheep to three different mixtures of PCB 153 and PCB 118 affected fetal testis development. Ewes were treated by oral gavage from mating until euthanasia (d 134), producing three groups of fetuses with distinct adipose tissue PCB levels: high PCB 153/low PCB 118 (n = 13), high PCB 118/low PCB 153 (n = 14), and low PCB 153/low PCB 118 (n = 14). Fetal testes and blood samples were collected for investigation of testosterone, testis morphology, and testis proteome. The body weight of the offspring was lower in the high PCB compared to the low PCB group, but there were no significant differences in testis weight between groups when corrected for body weight. PCB exposure did not markedly affect circulating testosterone. There were no significant differences between groups in number of seminiferous tubules, Sertoli cell only tubules, and ratio between relative areas of seminiferous tubules and interstitium. Two-dimensional (2D) gel-based proteomics was used to screen for proteomic alterations in the high exposed groups relative to low PCB 153/low PCB 118 group. Twenty-six significantly altered spots were identified by liquid chromatography (LC)–mass spectroscopy (MS)/MS. Changes in protein regulation affected cellular processes as stress response, protein synthesis, and cytoskeleton regulation. The study demonstrates that in utero exposure to different environmental relevant PCB mixtures exerted subtle effects on developing fetal testis proteome but did not significantly disturb testis morphology and testosterone production.     

Lactational fenvalerate exposure permanently impairs testicular development and spermatogenesis in mice

Fenvalerate, a widely used synthetic pyrethroid insecticide, has been associated with poor semen quality in human being. However, little is known about the effects of lactational fenvalerate exposure on testicular development and spermatogenesis. The purpose of the present study was to investigate the effects of maternal fenvalerate exposure during lactation on testicular development and spermatogenesis in male offspring. Maternal mice were administered with fenvalerate (60 mg/kg) by gavage daily from postnatal day (PND) 0 to PND21. Lactational fenvalerate exposure markedly decreased the absolute and relative weights of testes and increased the number of apoptotic cells in testes of pups at weaning. Histological examinations showed abnormal seminiferous tubules with large vacuoles or complete spermatogenic failure in testes of fenvalerate-treated mice at weaning. Additional experiment showed that lactational fenvalerate exposure markedly reduced mRNA and protein levels of testicular P450scc, a testosterone (T) synthesis enzyme. Consistent with down-regulation of testicular P450scc, the level of serum and testicular T at weaning was significantly decreased in pups whose mothers were exposed to fenvalerate during lactation. Although the expression of testicular P450scc and serum and testicular T in adulthood restored to control level, the decreased weight of testes and histological changes were irreversible. Importantly, the percentage of mature seminiferous tubules (stages VII and VIII) and the number of spermatozoa were obviously decreased in adult male mice whose mothers were exposed to fenvalerate during lactation. Taken together, these results suggest that lactational fenvalerate exposure permanently impairs testicular development and spermatogenesis.     

Maternal cypermethrin exposure during lactation impairs testicular development and spermatogenesis in male mouse offspring

Within the last decade, numerous epidemiological studies have demonstrated that endocrine disruptors are a possible cause for a decline in semen quality. Cypermethrin is a widely used pyrethroid insecticide, but little is known about its potentially adverse effects on male reproduction. In the present study, we investigated the effects of maternal cypermethrin exposure during lactation on testicular development and spermatogenesis in male offspring. Maternal mice were administered with cypermethrin (25 mg/kg) by gavage daily from postnatal day 0 (PND0) to PND21. Results showed that the weight of testes at PND21 was significantly decreased in pups whose mothers were exposed to cypermethrin during lactation. Maternal cypermethrin exposure during lactation markedly decreased the layers of spermatogenic cells, increased the inside diameter of seminiferous tubules, and disturbed the array of spermatogenic cells in testes of pups at PND21. In addition, maternal cypermethrin exposure during lactation markedly reduced mRNA and protein levels of testicular P450scc, a testosterone (T) synthetic enzyme. Correspondingly, the level of serum and testicular T at weaning was significantly decreased in pups whose mothers were exposed to cypermethrin during lactation. Although the expression of testicular T synthetic enzymes and serum and testicular T in adulthood had restored to control level, the decreased testicular weight and histological changes were irreversible. Importantly, the number of spermatozoa was significantly decreased in adult male offspring whose mothers were exposed to cypermethrin during lactation. In conclusion, maternal cypermethrin exposure during lactation permanently impairs testicular development and spermatogenesis in male offspring, whereas cypermethrin‐induced endocrine disruption is reversible. © 2010 Wiley Periodicals, Inc. Environ Toxicol 2011.     

Pre- and postnatal exposure to low-dose diesel exhaust impairs murine spermatogenesis

We investigated whether pre- and postnatal low-dose exposure to diesel exhaust (DE) affects male reproductive function in mice. The DE concentration is less than that indicated as the environmental quality standard for suspended particulate matter (SPM) in Japan. ICR mice were exposed prenatally to low-dose diesel exhaust (0.17 mg of DE particles/m3) through the airway for 8 h/day in an exposure chamber from gestational day 2 until the examination. In the DE-exposed groups, normal sperm morphology in the epididymis was reduced (p?相似文献   

Pre- and postnatal exposure to low-dose diesel exhaust impairs murine spermatogenesis

We investigated whether pre- and postnatal low-dose exposure to diesel exhaust (DE) affects male reproductive function in mice. The DE concentration is less than that indicated as the environmental quality standard for suspended particulate matter (SPM) in Japan. ICR mice were exposed prenatally to low-dose diesel exhaust (0.17?mg of DE particles/m³) through the airway for 8?h/day in an exposure chamber from gestational day 2 until the examination. In the DE-exposed groups, normal sperm morphology in the epididymis was reduced (p?<?0.01), and seminiferous tubules showed degenerative changes in which the number of Sertoli cells was decreased (p?<?0.01). Those changes were observed at 6 and 12 weeks of age. Furthermore, ultrastructural studies revealed an increase in damaged mitochondria in Sertoli cells (p?<?0.001) and variform spermatozoa. These results indicate that pre- and postnatal exposure of low-dose DE is detrimental to Sertoli cell function and may cause abnormal spermatozoa.     

Perinatal exposure to diesel exhaust affects gene expression in mouse cerebrum

Many environmental toxins alter reproductive function and affect the central nervous system (CNS). Gonadal steroid hormones cause differentiation of neurons and affect brain function and behavior during the perinatal period, and the CNS is thought to be particularly susceptible to toxic insult during this period. It was, therefore, hypothesized that inhalation of diesel exhaust (DE) during the fetal or suckling period would disrupt the sexual differentiation of brain function in mice, and the effects of exposure to DE during the perinatal period on sexual differentiation related gene expression of the brain were investigated. In the fetal period exposure group, pregnant ICR mice were exposed to DE from 1.5 days post-coitum (dpc) until 16 dpc. In the neonatal period exposure group, dams and their offspring were exposed to DE from the day of birth [postnatal day (PND)-0] until PND-16. Then, the cerebrums of males and females at PND-2, -5, and -16 from both groups were analyzed for expression level of mRNA encoding stress-related proteins [cytochrome P450 1A1 (CYP1A1), heme oxygenase-1 (HO-1)] and steroid hormone receptors [estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta), androgen receptor (AR)]. Expression levels of ER alpha and ER beta mRNA were increased in the cerebrum of newborns in the DE exposure groups as well as mRNA for CYP1A1 and HO-1. Results indicate that perinatal exposure to DE during the critical period of sexual differentiation of the brain may affect endocrine function.     

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。     

Chronic occupational lead exposure and testicular endocrine function

The effects of moderate lead exposure on testicular endocrine function were evaluated in a group of 90 males who were occupationally exposed to inorganic lead. Lead concentrations in blood and bone were measured as indices of short-term and long-term, cumulative exposure, respectively. The results of this study show that the lead exposure levels encountered in the UK at present may result in a subclinical increase in follicle stimulating hormone (FSH), which is related to blood lead levels. This suggest that lead may be causing some subclinical primary damage to the seminiferous tubules in the testes. However, at blood lead levels of less than 47 micrograms dl-1 this effect on serum FSH is not apparent. There was no significant effect on serum testosterone concentrations or the free testosterone index. The mean luteinizing hormone (LH) level in the exposed group was found to be lower than in the control population. However, there appeared a confoundingly significant positive correlation between serum luteinizing hormone levels and the length of occupational lead exposure within the exposed group.     

Glyphosate impairs male offspring reproductive development by disrupting gonadotropin expression

Sexual differentiation in the brain takes place from late gestation to the early postnatal days. This is dependent on the conversion of circulating testosterone into estradiol by the enzyme aromatase. The glyphosate was shown to alter aromatase activity and decrease serum testosterone concentrations. Thus, the aim of this study was to investigate the effect of gestational maternal glyphosate exposure (50 mg/kg, NOAEL for reproductive toxicity) on the reproductive development of male offspring. Sixty-day-old male rat offspring were evaluated for sexual behavior and partner preference; serum testosterone concentrations, estradiol, FSH and LH; the mRNA and protein content of LH and FSH; sperm production and the morphology of the seminiferous epithelium; and the weight of the testes, epididymis and seminal vesicles. The growth, the weight and age at puberty of the animals were also recorded to evaluate the effect of the treatment. The most important findings were increases in sexual partner preference scores and the latency time to the first mount; testosterone and estradiol serum concentrations; the mRNA expression and protein content in the pituitary gland and the serum concentration of LH; sperm production and reserves; and the height of the germinal epithelium of seminiferous tubules. We also observed an early onset of puberty but no effect on the body growth in these animals. These results suggest that maternal exposure to glyphosate disturbed the masculinization process and promoted behavioral changes and histological and endocrine problems in reproductive parameters. These changes associated with the hypersecretion of androgens increased gonadal activity and sperm production.     

Gonadal Effects of Fetal Exposure to the Azo Dye Congo Red in Mice: Infertility in Female but Not Male Offspring

The present study describes the relationship between gonadalagenesis and fertility in male and female mice exposed in uteroto the diazo dye Congo red (CR). Maternal CR treatment inhibitedtesticular and ovarian function in the offspring alter oraladministration of I or 0.5 g/kg/day on Gestational Days 8–12.The testes of male offspring from CR-exposed dams were smallin size and contained hypospermatogenic seminiferous tubules.However, despite the fact that testis weight was reduced bymore than 70% in some males, they displayed normal levels offertility when mated to untreated females for over 10 months.In contrast, female offspring from CR-exposed dams producedonly about half as many litters and pups as the control pairsdid under long- term mating conditions. Histological examinationof the ovaries revealed that subfertility was correlated withovarian atrophy. Females lacking maturing follicles were considerablyless productive (1.3 litters and 11.5 pups) than treated femaleswith histologically normal ovaries (7.1 litters and 78.1 pups).In sum mary, prenatal exposure to the dye CR affects the gonadsof both male and female offspring, but only the female offspringdisplay reduced fertility.     

雷公藤总碱对雄性大鼠的抗生育作用

雷公藤总生物碱(ATW)每日5,10,25,50,100mg/kg ig,每周给药6d,用药6wk后可见雄性大鼠睾丸曲细精管上皮细胞明显受损,随着剂量增加损害逐渐加重。病变以精子细胞及精母细胞为显著,并可干扰初级精母细胞核DNA的合成。对大鼠附睾及心、肝、脾、肺、肾等主要脏器的形态及功能无明显影响。在配对实验中,可见鼠的受孕率明显下降。停药8 wk后,大鼠睾丸受损的生精细胞有明显恢复。提示雷公藤总碱对大鼠有抗生育作用,有效剂量为25～50mg·kg~(-1)·d~(-1),其作用为可复性,对间质细胞分泌睾酮的功能无明显影响。     

Testicular toxicity of rats exposed to hexafluoroacetone (HFA) for 90 days

Rats were exposed to 0, 0.1, 1, and 12 ppm of hexafluoroacetone (HFA) for 6 h/day, 5 days/week for 90 days. The exposed rats were killed after 30 or 90 days exposure, and 28 or 84 days post-exposure (PE). There were no exposure-related pathological lesions in the rats exposed to 0.1 or 1.0 HFA for 90 days. After 30 days exposure to 12 ppm HFA, rats showed lower body weight gain, testicular atrophy, and oligospermia or aspermia in the epididymal tubules. At 30 days exposure, the atrophic testes had marked depletion of round spermatids in spermatogenic stages I-VIII and elongated spermatids in spermatogenic stages IX-XIV, but mature spermatids appeared only slightly decreased. Numerous spermatocytes in meiotic division in spermatogenic stage XIV were necrotic. At 90 days exposure, the testes showed severe atrophy with almost all seminiferous tubules affected and both immature and mature spermatids had disappeared from the seminiferous tubules. The epididymal tubules were devoid of spermatozoa. After 28 days PE, regeneration of atrophic testes was evident but varied markedly among the exposed rats. The number of seminiferous tubules producing elongated and mature spermatids was significantly lower than that of normal testes. Many seminiferous tubules had not regained normal spermatogenesis and the epididymal tubules showed marked oligospermia. After 84 days PE, normal spermatogenesis was still only partially restored to the atrophic testes, with many of the regenerating tubules still devoid of normal spermatogenesis.     

Influence of electromagnetic pulse on the offspring sex ratio of male BALB/c mice

Public concern is growing about the exposure to electromagnetic fields (EMF) and its effect on male reproductive health. Detrimental effect of EMF exposure on sex hormones, reproductive performance and sex-ratio was reported. The present study was designed to clarify whether paternal exposure to electromagnetic pulse (EMP) affects offspring sex ratio in mice. 50 male BALB/c mice aged 5–6 weeks were exposed to EMP daily for 2 weeks before mated with non-exposed females at 0d, 7d, 14d, 21d and 28d after exposure. Sex hormones including total testosterone, LH, FSH, and GnRH were detected using radioimmunoassay. The sex ratio was examined by PCR and agarose gel electrophoresis. The results of D0, D21 and D28 showed significant increases compared with sham-exposed groups. The serum testosterone increased significantly in D0, D14, D21, and D28 compared with sham-exposed groups (p < 0.05). Overall, this study suggested that EMP exposure may lead to the disturbance of reproductive hormone levels and affect the offspring sex ratio.     

Effects of chlorpyrifos on reproductive toxicology of male rats

The aim of this study is to investigate the effects of subchronic exposure to chlorpyrifos on reproductive toxicology of male rats. Forty healthy male rats were divided into four groups: three exposure groups and a control group. Chlorpyrifos was administered orally to male rats at 0, 2.7, 5.4, and 12.8mg/kg for 90 days to evaluate the toxic alterations in testicular histology, testicular marker enzyme activities and related genes expression levels, sperm dynamics, and testosterone levels. The body weight and the testis weight of animals did not show any significant changes. Chlorpyrifos brought about marked reduction in testicular sperm counts, sperm motility, and significant growth of sperm malformation rate in exposed males. Histopathological examination of testes showed mild to severe degenerative changes in seminiferous tubules at various dose levels. The levels of testosterone (T) showed a decreasing tendency, and there was a statistical difference between the 5.4, 12.8 mg/kg groups, and the control group. The levels of follicle stimulating hormone (FSH) were significantly increased in 5.4 and 12.8 mg/kg groups, but there were no obvious effects on the levels of luteinizing hormone (LH) and estradiol (E₂). A significant increase in the activities of LDH and LDH‐x was observed in chlorpyrifos exposed rats in 5.4 and12.8 mg/kg groups, but the expression levels of related genes had no significant differences between chlorpyrifos exposure groups and the control group. These results suggest that chlorpyrifos has adverse effects on reproductive system of male rats. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1083–1088, 2014.     

Chronic exposure to perfluorododecanoic acid disrupts testicular steroidogenesis and the expression of related genes in male rats

Perfluorododecanoic acid (PFDoA), a synthetic perfluorinated chemical, has been detected in environmental matrices, wildlife, and human serum. Its potential health risk for humans and animals has raised public concern. However, the effects of chronic PFDoA exposure on male reproduction remain unknown. The aim of this study was to determine the effects of chronic PFDoA exposure (110 days) on testosterone biosynthesis and the expression of genes related to steroidogenesis in male rats. In this study, we examined the serum levels of sex hormones, growth hormone, and insulin in male rats. Testicular morphology and the expression of key genes and proteins in testosterone biosynthesis were also analyzed. Markedly decreased serum testosterone levels were recorded after 110 days of PFDoA exposure at 0.2 mg PFDoA/kg/day and 0.5 mg PFDoA/kg/day, and cast-off cells were observed in some seminiferous tubules in testes exposed to 0.5 mg PFDoA/kg/day. PFDoA exposure resulted in significantly decreased protein levels of steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc), along with significantly reduced mRNA levels of insulin-like growth factor I (IGF-I), insulin-like growth factor I receptor (IGF-IR), and interleukin 1α (IL-1α) in rat testes at 0.2 mg/kg/day and 0.5 mg/kg/day. In addition, PFDoA exposure also affected the expression of some genes in the hypothalamo-neurohypophyseal system. However, PFDoA did not affect the expression of 5α-reductase, 3α-hydroxysteroid dehydrogenase, or aromatase in testis and liver. These findings demonstrate that chronic PFDoA exposure disrupts testicular steroidogenesis and expression of related genes in male rats. Multiple factors may be involved in the inhibition of testosterone by PFDoA.