Maternal exposure to butyl paraben impairs testicular structure and sperm quality on male rats

Parabens are hormonally active chemicals widely used as preservatives in foods and are frequently detected in human fluids and tissues. Therefore, the objective of this study was to determine the effects of maternal butyl paraben (BP) exposure on male sexual development. Pregnant Wistar rats received corn oil (control group), or BP at doses of 10, 100, or 200 mg/kg, subcutaneously, from gestational day 12 until postnatal day 21. Our results demonstrated that developmental BP exposure significantly increased the number of adult Leydig cells and the circulating concentrations of testosterone and attenuated FSH and LH concentrations at 200 mg/kg. BP exposure adversely affected spermatogenesis kinetics at doses of 10 and 200 mg/kg and provoked a decrease in the immunostaining of EsR1 and AR at 200 mg/kg. The sperm motility was impaired at the 10 mg/kg dose, and sperm head abnormalities were increased in all BP dose groups. We suggest that BP impairs testicular structure and function in the rat, affecting sperm quality. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1273–1289, 2017.     

Reproduction recovery of the crustacean Daphnia magna after chronic exposure to ibuprofen

In mammals, the pharmaceutical ibuprofen (IB), a non-steroidal anti-inflammatory drug, primarily functions by reversibly inhibiting the cyclooxygenase (COX) pathway in the synthesis of eicosanoids (e.g. prostaglandins). Previous studies suggest that IB may act in a similar manner to interrupt production of eicosanoids reducing reproduction in the model crustacean Daphnia magna. On this basis withdrawal of IB should lead to the recovery of D. magna reproduction. Here we test whether the effect of IB is reversible in D. magna, as it is in mammals, by observing reproduction recovery following chronic exposure. D. magna (5-days old) were exposed to a range of IB concentrations (0, 20, 40 and 80 mg l⁻¹) for 10 days followed by a 10 day recovery period in uncontaminated water. During the exposure period, individuals exposed to higher concentrations produced significantly fewer offspring. Thereafter, IB-stressed individuals produced offspring faster during recovery, having similar average population growth rates (PGR) (1.15–1.28) to controls by the end of the test. It appears that maternal daphnids are susceptible to IB during egg maturation. This is the first recorded recovery of reproduction in aquatic invertebrates that suffered reproductive inhibition during chronic exposure to a chemical stressor. Our results suggest a possible theory behind the compensatory fecundity that we referred to as ‘catch-up reproduction’.     

Bupropion treatment increases epididymal contractility and impairs sperm quality with no effects on the epididymal sperm transit time of male rats

Bupropion is a dopamine (DA) and norepinephrine (NE) reuptake inhibitor used as smoking cessation and antidepressant drug with a lower incidence of male sexual dysfunction. We showed previously that sibutramine, a norepinephrine/serotonine reuptake inhibitor, reduced male rat fertility. As there are no studies evaluating the impact of bupropion treatment on spermatic parameters and male fertility, we evaluated the effects of bupropion treatment (15 and 30 mg kg^?1, 30 days) on sexual behavior, spermatic parameters and fertility of male Wistar rats and on the epididymal duct in vitro contractility. Bupropion 15 mg kg^?1 increased the serum luteinizing hormone level and the epididymal duct contractility, but the sperm quality was not affected. At 30 mg kg^?1 bupropion impaired sperm quality increasing the incidence of non‐progressive sperm. The male sexual behavior and fertility were not modified at both bupropion doses. These results, in rats, suggest the importance of studies evaluating the effects of bupropion on the human male sperm quality. Copyright © 2015 John Wiley & Sons, Ltd.     

Continuous exposure to dibromoacetic acid delays pubertal development and compromises sperm quality in the rat.

Previously our work on the haloacid by-products of drinking water disinfection focused on adult exposures. Herein we evaluate the consequence of continuous exposure to dibromoacetic acid (DBA) via drinking water through reproductive development into adulthood. An initial study in which offspring were exposed from gestation day (GD) 15 through adulthood revealed significant delays in preputial separation and vaginal opening, dose-related decreases in the fertility of cauda epididymal sperm, and dose-related diminutions in the sperm membrane protein SP22. Subsequent studies consisted of groups in which exposure ceased on postnatal day 21 (PND 21) versus adulthood. For each exposure, animals were evaluated after puberty (PND 56) as well as at adulthood (PND 120). Exposure to 4, 40, or 400 ppm DBA from GD 15 through PND 21 failed to result in any significant reproductive alterations. By contrast, continuous exposure until adulthood resulted in dose-related alterations consistent with those observed in the dose-finding study. Preputial separation and vaginal opening were delayed 4 and 3 days in males and females exposed to 400 ppm (76.3 mg/kg) DBA. This was associated with increased responsiveness of both the testis and ovary to hCG ex vivo; hCG-stimulated testosterone production by testicular parenchyma on PND 56 was increased at 4 ppm (0.6 mg/kg) DBA and higher. Finally, the quality of proximal cauda epididymal sperm was compromised by continuous exposure to DBA. The sperm membrane proteome was altered in a dose-related manner with SP22, and one of its charged variants, diminished at 40 ppm (3.6 mg/kg) DBA and higher. As more sensitive endpoints are evaluated, lower effect levels can be attributed to haloacid exposure. We are now extending our evaluations to epidemiology studies designed to evaluate sperm quality in men exposed to varying levels of disinfection by-products.     

Daily exposure to silver nanoparticles during prepubertal development decreases adult sperm and reproductive parameters

Abstract

As silver nanoparticles (AgNPs) have antimicrobial properties and potentiate the activity of some antibiotics, they are broadly used in both medical and nonmedical applications. In this study, prepubertal male Wistar rats were orally treated with 15 or 30?µg/kg/day AgNPs from postnatal day 23 (PND23) to PND58 and sacrificed at PND102. The acrosome integrity, plasma membrane integrity, mitochondrial activity and morphological alterations of the sperm were analyzed. Sexual partner preference, sexual behavior and the serum concentrations of FSH, LH, testosterone and estradiol were also recorded. The results were evaluated following the appropriate statistical analyses, and differences among the groups were considered significant when p?<?0.05. AgNPs reduced the acrosome and plasma membrane integrities, reduced the mitochondrial activity and increased the abnormalities of the sperm in both treatment groups. AgNP exposure also delayed the onset of puberty, although no changes in body growth were observed in either treatment group. The animals did not show changes in sexual behavior or serum hormone concentrations. This study shows for the first time that prepubertal exposure to AgNPs causes alterations in adult sperm parameters. Importantly, the sperm appeared to be more sensitive to the toxic effects of AgNPs and demonstrated adverse effects following exposure to lower doses. Consequently, the effects of AgNPs on sperm should be considered in order to establish safety limits for the use of these particles.     

Arsenic trioxide exposure impairs testicular morphology in adult male mice and consequent fetus viability

ABSTRACT

The acute promyelocytic leukemia (APL) is a rare disease, affecting 0.1/100,000 individuals globally. Despite significant advances in APL therapy, some patients still experience relapsed disease. Currently, arsenic trioxide (As₂O₃) was found to be effective in relapsed APL treatment and considered as standard treatment for these cases. However, it has been shown that exposure to As₂O₃ may exert adverse effects on the male reproductive system since this substance might also induce apoptosis of other important cell types including stem cells. Studies demonstrated that treatment with this metallic substance decreased plasma levels of testosterone and interfered with sperm parameters such as concentration, motility, and viability. In addition, As₂O₃ was found to produce significant damage to spermatocytes, which may be associated with testicular toxicity and consequent inhibition of spermatogenesis. The aim of this study was to determine sub-chronic treatment effects of As₂O₃ on sperm and testicular morphology, androgen receptor (AR) immunoreactivity in testes and epididymis, in addition to evaluation of fertility parameters in adult male mice. Thirty adult Swiss mice were divided into three experimental groups: control; received distilled water (vehicle) while treated received 0.3 or 3 mg/kg/day As₂O₃ subcutaneously, for 5 days per week, followed by 2 days of interruption, for 5 weeks. Results showed that As₂O₃ (1) decreased spermatozoa number, (2) produced seminiferous epithelium degeneration and exfoliation of germ cells tubule lumen (3) altered nucleus/cytoplasm proportion of Leydig cells and (4) reduced AR immunoreactivity in both Leydig and epithelial epididymal cells. Further, fetal viability tests demonstrated an increase in post-implantation loss in females that were mated with As₂O₃-treated males. Data indicate that As₂O₃ exposure altered the spermatogenic process and subsequently fetal viability.     

Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats

In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n?=?5/group) weighing 180–250?g were used. First group served as control, second group received arsenic (50?ppm) in drinking water. Third group was treated with quercetin (50?mg/kg) alone, while fourth group received arsenic?+?quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic?+?quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic?+?quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage.     

Maternal exposure to the antidepressant fluoxetine impairs sexual motivation in adult male mice

Depressive disorders have a worldwide high prevalence. Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) antidepressant, has been widely prescribed for depression during pregnancy and/or lactation. Since serotonin is a neurotrophic factor, the use of FLX by mothers could disrupt brain development resulting in behavioral alterations in their progeny. The aim of the present study was to evaluate the effects of developmental FLX exposure on sexual behavior, as well as on endocrine parameters, of male mice. Swiss dams were treated daily, by gavage, with 7.5 mg/kg of FLX during pregnancy and lactation. Male pups were tested for copulatory behavior and sexual incentive motivation. Male pups also had their anogenital distance, plasmatic testosterone concentration and testis, epididymis, seminal vesicle and pituitary wet weights assessed. Copulatory behavior, anogenital distance, plasmatic testosterone concentration and organs wet weights were not affected by FLX exposure. However, this exposure eliminated preference for a sexual incentive on the sexual incentive motivation test, which indicates reduced sexual motivation, a classic side effect of SSRIs in humans who take these antidepressants.     

Effect of prenatal administration of NSAIDs on the immune response in juvenile and adult rats

In order to investigate the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the development of rat immunity, indomethacin (IND; 0.25, 0.5, or 1.0 mg/kg/day), acetyl salicylic acid (ASA; 90, 180, or 360 mg/kg/day), or diclofenac sodium salt (DSS; 0.5, 1.0, or 2.0 mg/kg/day) suspended in 0.5% methylcellulose aqueous solution, was orally administered once daily to five pregnant Sprague-Dawley (IGS) rats per group on days 18-21 of gestation. After parturition, the serum IgM and IgG levels, the spleen weight, and the number of spleen cells were measured in 3- and 8-week-old pups. Afterwards, immunophenotyping analysis of splenocytes or peripheral blood lymphocytes and T-dependent antibody response were performed. The number of spleen cells in 3-week-olds increased when 1.0 mg/kg of IND and 180 mg/kg of ASA were administered. Immunophenotyping analysis using flow cytometry (FCM) indicated that the proportion and number of CD45RA(+) cells increased, and the proportion of CD3(-) NKR-P1A(+) cells decreased in males when dosed with IND at 1.0 mg/kg or ASA at 180 mg/kg. The serum anti-KLH IgG antibody titer decreased in the males of the IND 1.0 mg/kg dosing group, the serum levels of anti-KLH IgM, total IgM, and IgG were not changed at all. These changes disappeared in 8-week-old pups. There were no effects on any of the parameters in the 3- and 8-week-olds of the DSS treatment group. These results suggest that IND or ASA administration to dams during late gestation either causes a change in the lymphocyte subsets, or that they suppress the T-dependent antibody response in juvenile males. Both of these changes eventually recover to intact levels later on during development. These results will contribute to the development of a technique for the assessment of developmental immunotoxicity and generate data on the effect of prenatal administration of NSAIDs on the developmental immune system in pups.     

Effects of indium chloride exposure on sperm morphology and DNA integrity in rats

Indium, a Group IIIA element of the periodic chart and a rare earth metal characterized by high plasticity, corrosion resistance, and a low melting point, is widely used in the electronics industry where released streams can contaminate the environment. Consequently, indium can reach humans mainly by natural ways, which could result in a health hazard. Although reproductive toxicities have been surveyed in some studies in animal models, the infertility effects of sperm function induced by indium compounds have not been greatly investigated. We designed a study to investigate the toxicities of subacute exposure to indium compounds on male sperm function and the process of spermatogenesis in a rodent model. Fourteen Sprague-Dawley rats on postnatal Day (PND) 84 were randomly divided into exposure and control groups, and weekly received intraperitoneal injections of indium chloride (1.5 mg/kg body weight) and normal saline, respectively, for 8 weeks. Cauda epididymal sperm count, motility, morphology, chromatin DNA integrity, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and testis DNA content were investigated. The indium chloride exposed group showed significant toxicity to sperm function, as well as an increased percentage of sperm morphological abnormality and chromatin DNA damage. Furthermore, positive correlations between abnormal sperm morphology, chromatin DNA damage, and superoxide anion generation were also noted. The results of this study demonstrated the toxic effect of subacute low dose indium exposure during sexual maturation on sperm function, resulting in sperm chromatin DNA damage through an increase in sperm ROS generation in a rodent model.     

Spermatogenesis and epididymal sperm after scrotal gamma irradation in adult rats

Quantitative histologic evaluation was performed on the testes of albino rats exposed to scrotal gamma irradiation of 2.5 Gy and 10.0 Gy. The animals were sacrificed at 1, 2, 4, and 16 weeks posttreatment. As a result of irradiation, there was a gradual decrease in testicular weight. The seminiferous tubules of irradiated animals showed arrest of spermatogenesis, desquamation, vacuolization of germinal cells, and multinucleated giant cells. The extent of damage increased with posttreatment interval and with increasing dose. Counting of germinal cells at stage VII of the seminiferous epithelium revealed that the preleptotene spermatocyte is the most sensitive to radiation as compared to other cells. The number of epididymal sperm decreased, whereas the proportion of nonmotile and morphologically abnormal sperm increased following irradiation.     

Triclosan exhibits a tendency to accumulate in the epididymis and shows sperm toxicity in male sprague‐dawley rats

Triclosan (TCS) is considered a potent endocrine disruptor that causes reproductive toxicity in non‐mammals, but it is still unclear exactly whether TCS has adverse effects on the sperm or reproductive organs in mammals. In this study, we aimed to evaluate the distribution status of TCS in male reproductive organs of rats, and seek the correlation with the TCS‐induced sperm toxicity or reproductive organ damage. Male rats were intragastrically administered with TCS at a dose of 50 mg/kg, the kinetics of TCS in the plasma and reproductive organs were investigated. TCS in testes and prostates both showed a lower‐level distritbution compared to that in the plasma, which indicates it has no tendency to accumulate in those organs. However, TCS in the epididymides showed a longer elimination half‐life (t_1/2z), a longer the mean retention time (MRT), and a lower clearance (CL_Z/F) compared with those in the plasma. Besides, the ratios of mean area under the concentration‐time curve (AUC)_{0–96h(epididymides/plasma)} and AUC_{0–∞(epididymides/plasma)} were 1.13 and 1.51, respectively. These kinetic parameters suggest TCS has an accumulation tendency in the epididymides. Based on this, we investigated the TCS‐induced sperm toxicity and histopathological changes of reproductive organs in rats. TCS was given intragastrically at doses of 10, 50, and 200 mg/kg for 8 weeks. Rats treated with the high dose (200 mg/kg) of TCS showed a significant decrease in daily sperm production (DSP), changes in sperm morphology and epididymal histopathology. Considering the histopathological change in the epididymides, TCS may induce the epididymal damage due to the epididymal accumulation of that. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 83–91, 2015.     

Anethole compromises human sperm function by affecting the sperm intracellular calcium concentration and tyrosine phosphorylation

Anethole is a natural anisole derivative that has been widely used in food and daily chemical industries, agricultural applications and the traditional medicine. It is closely related to aspects of daily life, and humans can easily be exposed to it. Although the reproductive toxicity of anethole was shown in the rat, its effect on human reproduction remains unknown. In this study, we examined the effect of anethole on human sperm in vitro. Different anethole doses (0.1, 1, 10, and 100 μM) were applied to ejaculated human sperm. Fertilization-essential functions, as well as the intracellular calcium concentration ([Ca²⁺]_i) and tyrosine phosphorylation, two vital factors for regulating sperm function, were measured. The results indicated that 10 and 100 μM anethole significantly reduced the motility, hyperactivation, and penetration ability of human sperm (P < 0.05) and inhibited the increase in human sperm functions induced by progesterone, a hormone essential for sperm function activation. Additionally, 10 and 100 μM anethole decreased both basal and progesterone-increased tyrosine phosphorylation, [Ca²⁺]_i, and the current of CATSPER, a cation channel of sperm predominant for Ca²⁺ influx. These results suggest that anethole inhibits human sperm functions by reducing sperm [Ca²⁺]_i through CATSPER and suppressing tyrosine phosphorylation in vitro, raising the fact that the caution is needed when overtaking anethole.     

棉酚造成大鼠精子质量下降与NO之间关系的研究

目的阐明棉酚造成精子质量下降的生化机制,为其应用和降低毒副作用提供新思路。方法采用Wistar大鼠口服给予棉酚(50mg·kg-1/2d),2wk后取附睾尾精子,采用CASA进行检测,同时对血清中的促黄体生成素(LH),促卵泡生成素(FSH)、睾酮(T)进行检测,对睾丸组织形态学以及组织内的一氧化氮(NO)含量进行检测。结果棉酚可造成精子的数量减少,活力降低。睾丸组织内部结构紊乱,睾丸组织中的NO水平上升,血清中的T下降,而对FSH、LH无影响。化合物NA1108可拮抗棉酚造成的精子质量下降,降低睾丸内NO含量,升高血清中T含量。结论棉酚造成精子质量降低的机制之一是由于其造成睾丸组织内NO的过量产生,从而损伤睾丸组织内的多种细胞所致,能降低睾丸内NO含量的药物可提高精子质量。     

Gestational-lactational exposure to Aroclor 1254 impairs radial-arm maze performance in male rats.

Developmental exposure to polychlorinated biphenyls (PCBs) has been associated with cognitive deficits in children. The current study assessed effects of gestational and lactational exposure to a commercial PCB mixture, Aroclor 1254 (A1254), on spatial learning and memory in rats, using the radial-arm maze (RAM). Pregnant Long-Evans females (10/dose group) were exposed to 0 or 6-mg/kg/day A1254 (po in corn oil) from gestation day (GD) 6 to weaning at postnatal day (PND) 21. After they reached adulthood, 1 male and 1 female from each litter were tested on a working/reference memory task using a 12-arm RAM. Eight of the 12 arms were baited, with the pattern of baited arms remaining the same on every trial for each rat. Compared to control males, the A1254-exposed males made significantly more working memory errors (2.15 +/- 0.13 and 3.20 +/- 0.18 errors +/- SEM for control and A1254 males, respectively) and reference memory errors (3.17 +/- 0.10 and 4.13+/-0.14 errors +/- SEM for control and A1254 males, respectively) on the RAM. In contrast, A1254-exposed females were not impaired relative to control females on the RAM. Drug challenges with dizocilpine (MK-801) and scopolamine did not differentially affect working or reference memory of control and exposed rats. These data suggest that perinatal exposure to A1254 may cause sex-specific deficits in spatial learning and memory, and that NMDA-mediated and muscarinic neurotransmission, as assessed with the drug challenges, were not markedly impaired in the A1254-exposed animals.     

Effects of isolated or combined exposure to sibutramine and rosuvastatin on reproductive parameters of adult male rats

Many obese patients are exposed to hypolipidemic and serotonin-norepinephrine reuptake inhibitor (SNRI) drugs. Statins are one of the most marketed drugs in the world to treat dyslipidemia, while sibutramine, a SNRI drug, is prescribed in some countries to treat obesity and is detected as an additive in many adulterated weight loss supplements marketed worldwide. Previous studies reported adverse effects of isolated exposure to these drugs on male rat reproductive parameters. In the present work, we further investigated male reproductive toxicity of these drugs, administered in isolation or combination in adult rats for a longer period of treatment. Adult male rats (90 days) were treated (gavage) for 70 days with saline and dimethyl sulfoxide (control), sibutramine (10 mg/kg), rosuvastatin (5 mg/kg), or rosuvastatin combined with sibutramine. Sibutramine alone or with rosuvastatin, promoted a reduction in food intake and body weight gain, weight of the epididymis, ventral prostate and seminal vesicle; as well as decreased sperm reserves and transit time through the epididymis; androgen depletion; and increased index of cytoplasmic droplet. The rosuvastatin-treated group showed reduced frequency of ejaculation. Exposure to this drug alone or combined with sibutramine impaired epididymal morphology. Co-exposed rats had altered epididymal morphometry, and seminal vesicle and testis weights. The rats also showed decreased fertility after natural mating and a trend toward a delay in ejaculation, suggesting a small synergistic effect of these drugs. Given the greater reproductive efficiency of rodents, the results obtained in the present study raise concern regarding possible fertility impairment in men taking statins and SNRI drugs.     

Evaluation of reproductive parameters in adult male Wistar rats after subchronic exposure (gavage) to benomyl

Proven-breeder 102-d-old male Wistar rats were gavaged daily with 0, 1, 5, 15, or 45 mg/kg.d benomyl. The animals were bred to untreated females after 62 d and killed after 76-79 d for evaluation of selected male reproductive end points. Minimal to moderate changes were observed in rats dosed with 45 mg/kg.d; these included decreased testis and epididymis weight, reduced cauda sperm reserves, decreased sperm production, increased numbers of decapitated spermatozoa, and increased numbers of seminiferous tubules containing multinucleated giant cells. Reproductive performance, seminal vesicle and prostate weight, sperm motility, serum luteinizing hormone, follicle-stimulating hormone, prolactin, and androgen binding protein were not affected by any of the dosages tested. Based on these end points, the no-effect level was 15 mg/kg.d.     

萘普替尼对雄性大鼠睾丸形态结构和附睾精子质量的影响

目的 探究萘普替尼对雄性大鼠睾丸形态结构及附睾精子质量的影响。方法 将30只雄性SD大鼠随机分为30和70 d两组,每组又分为对照组和萘普替尼低、高剂量组（0.75、3.00 mg/kg）,ig给药,每天给药1次,给药体积10 mL/kg。每天进行1次症状观察,每周称量一次体质量,大鼠分别于给药35和70 d后次日处死,肉眼检查各脏器有无异常,检测双侧睾丸质量和横径、附睾尾精子数量和活力,睾丸固定进行组织病理学检查。结果 萘普替尼高剂量组动物均从给药第14天开始,出现腹泻、脱毛、口鼻眼处有红色分泌物,随着给药天数的增加,症状加重;给药70 d组其中1只动物于给药60 d开始出现血尿症状。给药35 d组大鼠从给药21 d开始,给药70 d组从14 d开始,高剂量大鼠体质量明显低于同期对照组（P<0.01）。与对照组比较,给药组雄鼠的双侧睾丸绝对质量和脏器指数、睾丸横径、附睾尾精子数量和活力及睾丸组织病理学检查并未随给药剂量的增加和给药时间的延长而出现明显变化。结论 萘普替尼对雄性大鼠的睾丸组织及精子质量无明显影响。     

The adverse effects of low‐dose exposure to Di(2‐ethylhexyl) phthalate during adolescence on sperm function in adult rats

Di(2‐ethylhexyl) phthalate (DEHP) is the most crucial phthalate derivative added to polyvinyl chloride as a plasticizer. This study examined the effects of low‐dose exposure to DEHP during adolescence on sperm function in adult rats. The male rats were daily gavaged with 30, 100, 300, and 1000 µg kg^?1 of DEHP or corn oil from postnatal day (PND) 42 until PND 105. The selection of DEHP doses ranged from the mean daily intake by the normal‐population exposure levels to no‐observed‐adverse‐effect level of DEHP for the endpoints evaluated until adulthood. Significant increases in the percentage of sperm with tail abnormality, tendency for sperm DNA fragmentation index (DFI) and percentage of sperm with DFI were found in those exposed to 100, 300, and 1000 µg kg^?1 (P < 0.05). We observed a significant increase of hydrogen peroxide (H₂O₂) generation in the sperm of the 1000 µg kg^?1 group compared with the control group (P < 0.05). The excessive production of sperm H₂O₂ coincided with an increase in sperm DFI. In this study, the lowest‐observed‐adverse‐effect level for sperm toxicity was considered to be 100 µg DEHP/kg/day in sperm morphology and chromatin DNA damage. Further research is necessary to clarify the mechanisms of DEHP‐related sperm ROS generation on sperm DNA damage. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 706–712, 2016.     

Paternal treatment with cisplatin impairs reproduction of adult male offspring in rats

This study evaluated the acute and persistent effects of paternal cisplatin-treatment on progeny. Wistar male rats (45 days old) were assigned into 2 groups. Control and cisplatin (CP: 1 mg/kg-d, 5 days/week, for 3 weeks, ip.). Male rats at 66 (end of treatment, acute effects evaluation) and 140 days old (after recovery period, persistent effects evaluation) were mated with females. Fetal and post-natal developments of the offspring sired by treated-male mated in both ages were evaluated, including fertility of adult male offspring. No adverse effects in fetal development or puberty onset were seen in CP offspring. However, testicular descent was delayed and postnatal growth was impaired in these animals (acute effect). Moreover, seminal vesicle weight and epididymal sperm count from adult progeny were affected (acute effects) by paternal CP-exposure. The only persistent effect found was alterations in the spermatogenesis. We conclude that paternal CP-administration during peri-puberty affects reproductive endpoints of the progeny.