Grape Seed Proanthocyanidin Extract Alleviates Arsenic-induced Oxidative Reproductive Toxicity in Male Mice

Objective To determine the ability of grape seed proanthocyanidin extract （GSPE） in alleviating arsenic-induced reproductive toxicity. Methods Sixty male Kunming mice received the following treatments by gavage： normal saline solution （control）; arsenic trioxide （ATO; 4 mg/kg）; GSPE （400 mg/kg）; ATO＋GSPE （100 mg/kg）; ATO＋GSPE （200 mg/kg） and ATO＋GSPE （400 mg/kg）. Thereafter, the mice were sacrificed and weighed, and the testis was examined for pathological changes. Nuclear factor （erythroid-derived 2）-like 2 （Nrf2）, heme oxygenase 1 （HO1）, glutathione S-transferase （GST）, NAD（P）H dehydrogenase, and quinone 1 [NQO1） expression in the testis was detected by real-time PCR. Superoxide dismutase （SOD）, glutathione （GSH）, total antioxidative capability （T-AOC）, malondialdehyde （MDA）, 8-hydroxydeoxyguanosine （8-OHdG）, and reproductive indexes were analyzed. Results ATO-treated mice showed a significantly decreased sperm count and testis somatic index and activity levels of SOD, GSH, and T-AOC than control group. Compared to the ATO-treated group, ATO ＋GSPE group showed recovery of the measured parameters. Mice treated with ATO＋high-dose GSPE showed the highest level of mRNA expression of Nrf2, HO, NO.O1, and GST. Conclusion GSPE alleviates oxidative stress damage in mouse testis by activating Nrf2 signaling, thus counteracting arsenic-induced reproductive toxicity.

Developmental and Reproductive Toxicity of Soybean Isoflavones to Immature SD Rats

Objective To investigate the dose-dependent toxic effect of soybean isoflavone extracts （SIE） on reproductive development in immature rats. Methods Growing male and female rats （n=50 each, 4 weeks） were divided into five groups fed with a standard cereal-based diet and gastrogavaged daily with 0, 30, 150, 300, and 600 mg SIE / kg body weight, respectively, for 12 weeks. Body weight, organ weights, and serum level of estrogen and testosterone were measured. Results Oral administration of SIE had no effect on food intake but decreased food efficiency ratio （P〈0.01）. Suppression on body weight gain by SIE was dose-dependent and the effect was greater on male than on female rats （P〈0.01）. SIE at high doses exhibited hepatotoxicity by increasing a relative liver weight, and also caused a smaller uterus but a greater relative ovary in female rats, while leading to larger relative testis and epididymis in male rats. SIE could decrease progesterone concentrations in female rats, whereas in male rats it reduced not only total testosterone level but also sperm count compared with the control group （P〈0.05）. Conclusion SIE at a range of 50-1000 times of human intake level affects not only growth but also development of reproductive system in growing rats.

Effects of Roselle and Ginger on cisplatin-induced reproductive toxicity in rats

Aim： To evaluate the protective effects of Hibiscus sabdariffa （Roselle） and Zingiber officinale （Ginger） against cisplatin-induced reproductive toxicity in rats and to study the mechanisms underlying these effects. Methods： Ethanol extracts of H. sabdariffa or Z. officinale [1 g/（kg·day）] were given p.o. to male albino rats for 26 days, which began 21 days before a single cisplatin i.p. injection （10 mg/kg body weight）. Results： Extracts of H. sabdariffa and Z. offcinale reduced the extent of cisplatin-induced sperm abnormality and enhanced sperm motility. Both extracts restored the control level of malondialdehyde （MDA） （lipid peroxidation marker） in the cisplatin-treated testis. The cisplatin injection induced decline in the levels of superoxide dismutase （SOD）, reduced glutathione （GSH） and catalase （CAT） were significantly reversed to control levels in groups where cisplatin was preceded by the administration of either H. sabdariffa or Z. officinale. Conclusion： Both H. sabdariffa and Z. officinale treatment increased the activities of testicular antioxidant enzymes and restored sperm motility of cisplatin-treated rats. The protective effects of tested plants are, therefore, suggested to be mediated by their potent antioxidant activities.

Glycerin Monostearate Aggravates Male Reproductive Toxicity Caused by Di(2-ethylhexyl)Phthalate in Rats

Human beings are increasingly exposed to phthalates,which are a group of chemicals used to make plastics more flexible and harder to break,and simultaneously ingesting abundant food emulsifiers via daily diet.The purpose of this study was to investigate the effect of the food emulsifier glycerin monostearate(GMS)on male reproductive toxicity caused by di(2-ethylhexyl)phthalate(DEHP,one of the phthalates)and explore the underlying mechanism.Thirty male Sprague-Dawley rats were randomly divided into control group,DEHP group and DEHP+GMS group.Rats in the DEHP group and DEHP+GMS group were orally administered with 200 mg/kg/d DEHP with or without 20 mg/kg/d GMS.After 30 days of continuous intervention,it was found that the serum testosterone level was significantly lowered in DEHP group and DEHP+GMS group than that in control group(P<0.01).The serum testosterone level and the relative testis weight were significantly decreased in the DEHP+GMS group as compared with those in the DEHP group and control group(P<0.05).More spermatids were observed to be shed off in DEHP+GMS group than in DEHP group.The expression levels of cell cycle checkpoint kinase 1(Chkl),cell division cycle gene 2(Cdc2),and cyclin-dependent kinase 2(CDK2)were down-regulated in DEHP group,and this tendency was more significant in DEHP+GMS group(P<0.05 or P<0.01).There was no significant difference in the P-glycoprotein(P-gp)expression between DEHP group and control group.However,P-gp was markedly down-regulated in DEHP+GMS group(P<O.Ol).The results indicated that the food emulsifier GMS aggravated the toxicity of DEHP on male reproduction by inhibiting the cell cycle of testicular cells and the expression of P-gp in testis tissues.

Acute and Reproductive Toxicity of the Aqueous Extract of the Dry Seeds of <i>Aframomum daniellii </i>on the Female Wistar Rat Strain

This work was designed to investigate the acute and reproductive toxicity activity of the aqueous extract of the dry seeds of Aframomum daniellii on the female rats. The acute toxicity of the aqueous extract of Aframomum daniellii (A. daniellii) was evaluated with 6 female rats which were divided into 2 groups (1 Test group and the Control group) of 3 female rats each. The control group received distilled water (10 mL/kg/po) and the test group received a single dose of extract of A. daniellii at the dose of 2000 mg/kg. The reproductive toxicity was evaluated using 45 adult female rats which were divided into 5 groups. Group I, received distilled water (1 mL/100 g/po, neutral control);group II, received Clomiphene citrate (600 μg/kg/po, positive control);Groups III, IV and V (trials) received aqueous extract of A. daniellii at doses of 100, 200 and 400 mg/kg/po respectively. The animals were treated daily for 14 days. From the 6th day of treatment, the rats were mated with males of proven fertility for 8 days. On day 22, after laparotomy and delivery, the number of implantation sites, corpora lutea, resorption sites and pups were recorded. Concerning the acute toxicity, it was observed that, after the single dose of 2000 mg/kg administration of the aqueous extract of the dry seeds of A. daniellii, no deaths were recorded. Concerning the reproductive toxicity, no implantation and gestation were observed when compared to the control. However, the aqueous extract of A. daniellii caused a significant (p < 0.001) increase in serum estrogen levels in all treated rats when compared to the control. These results indicate that, the aqueous extract of the dry seeds of A daniellii is weakly toxic, but could negatively affect some reproductive parameters.

Aqueous wood-ash extract of Parkia biglobosa causes reproductive toxicity in female mice

Background: The traditional culture of eating wood-ash extracts in some countries has led to many health problems.The study assessed the anti-fertility effects of the aqueous wood-ash extract of Parkia biglobosa on female Swissalbino mice. Methods: Healthy female albino mice were procured and randomly grouped into four groups (5/group)where control, 5, 50 and 100 mg/kg doses of the extract were orally administered for 20 days and microscopy ofvaginal smear carried out daily to determine anti-ovulatory activity. Oestrus cycle, including metestrus, diestrus andoestrus phases and histopathology of the uterus were examined daily and at the termination of the experiment.Results: At the end of the study, the highest number of circles (4.80 ± 0.20) was recorded in the control group,administered distilled water, while the lowest number of circles (3.00 ± 0.32) was in the 100 mg/kg dose group.Oestrus (5.80 ± 0.37) also is highest in the control group and lowest (1.20 ± 0.37) in the 100 mg/kg dose group. Thegroup administered 100 mg/kg dose of the aqueous wood-ash extract of Parkia biglobosa had the highest diestrusindex of 45, while the lowest of 17 was obtained in the control group. Histopathology of the uterus tissues shows afew degenerate epithelial cells in 50 mg/kg group and moderate dilatation of lumen and glandular epithelial cells in100 mg/kg group. Conclusion: The study revealed dose-dependent anti-fertility effects of the aqueous wood-ashextract of Parkia biglobosa on female albino mice, which implies its potential reproductive toxicity in humans.

Toxic Effects of Atrazine on Reproductive System of Male Rats

Objective This study was designed to evaluate the toxic effects of Atrazine （ATZ） on the reproductive system of male rats. 〈br〉 Methods Male Sprague-Dawley rats were exposed to ATZ by gavage at dosages of 0, 38.5, 77, and 154 mg/kg bw/day for 30 d. The toxic effects of ATZ to rats were assessed through histopathologcal observation, spermatozoa quality evaluation, testicular marker enzyme indicators, antioxidant capacity and reproductive hormone levels. Results Significant adverse effects on reproductive system were observed in rats exposed to ATZ at different dosages compared with 0 mg/kg group, including an irregular and disordered arrangement of the seminiferous epithelium in 154 mg/kg group;a decreased spermatozoa number and an increased spermatozoa abnormality rate in 77 and 154 mg/kg groups;decreased levels of acid phosphatase （ACP）, alkaline phosphatase （AKP）, lactic dehydrogenase （LDH）, and succinate dehydrogenase （SDH） with the increasing of ATZ concentration; a decreased level of total antioxidant capacity （TAC） in a dose-dependent manner, and a decreased reduced glutathione （GSH） level and an increased malondialdehyde （MDA） content in 154 mg/kg group;and decreased serum levels of testosterone （T） and inhibin-B （INH-B） and an increased serum level of follicle stimulating hormone （FSH） in 77 and 154 mg/kg groups, and an increased serum level of luteinizing hormone （LH） in 154 mg/kg group. Conclusion These results suggested that relatively high doses of ATZ could exert reproductive toxicity of male rats.

A single-cell landscape of triptolide-associated testicular toxicity in mice

Triptolide is a key active component of the widely used traditional Chinese herb medicine Tripterygium wilfordii Hook.F.Although triptolide exerts multiple biological activities and shows promising efficacy in treating inflammatory-related diseases,its well-known safety issues,especially reproductive toxicity has aroused concerns.However,a comprehensive dissection of triptolide-associated testicular toxicity at single cell resolution is still lacking.Here,we observed testicular toxicity after 14 days of triptolide exposure,and then constructed a single-cell transcriptome map of 59,127 cells in mouse testes upon triptolide-treatment.We identified triptolide-associated shared and cell-type specific differentially expressed genes,enriched pathways,and ligand-receptor pairs in different cell types of mouse testes.In addition to the loss of germ cells,our results revealed increased macrophages and the inflammatory response in triptolide-treated mouse testes,suggesting a critical role of inflammation in triptolide-induced testicular injury.We also found increased reactive oxygen species(ROS)signaling and downregulated pathways associated with spermatid development in somatic cells,especially Leydig and Sertoli cells,in triptolide-treated mice,indicating that dysregulation of these signaling pathways may contribute to triptolide-induced testicular toxicity.Overall,our high-resolution single-cell landscape offers comprehensive information regarding triptolide-associated gene expression profiles in major cell types of mouse testes at single cell resolution,providing an invaluable resource for understanding the underlying mechanism of triptolide-associated testicular injury and additional discoveries of therapeutic targets of triptolide-induced male reproductive toxicity.

Toxicity of perfluorononanoic acid and perfluorooctane sulfonate to Daphnia magna

In order to study toxicological effects of perfluorononanoic acid （PFNA）, perfluorooctane sulfonate （PFOS）, and their mixtures （PFNA/ PFOS） on Daphnia magna （D. magna）, a suite of comprehensive toxicity tests were conducted, including a 48-h acute toxicity test, a 21-day chronic test, a feeding experiment, and a biomarker assay. D. magna were exposed to aqueous solutions of PFNA and PFOS （alone and in combination） at concentrations ranging from 0.008 to 5 mg/L. The survival, growth, and reproduction of D. magna were monitored over a 21- day life cycle. The biomarkers, including acetylcholinesterase （ACHE）, superoxide dismutase （SOD）, and catalase （CAT） activities, were determined after seven days of exposure. PFOS was more toxic than PFNA based on the results of the acute toxicity test. Perfluorinated compounds （PFCs） inhibited both growth and reproduction of D. magna during the testing period. The ingestion rates and the biomarkers, including ACHE, SOD, and CAT activities, were significantly inhibited by PFCs in most cases. Moreover, the combined effects related to the growth and reproduction showed the antagonistic effects of PFCs.

Effects of Parental Dietary Exposure to GM Rice TT51 on the Male Reproductive System of Rat Offspring

Objective To evaluate the health effects of parental dietary exposure to GM rice TT52 on the male reproductive system of rat offspring. Methods Rice-based diets, containing 60% ordinary grocery rice, MingHui63, or TT51 by weight, were given to parental rats （15 males/30 females each group） for 70 days prior mating and throughout pregnancy and lactation. After weaning, eight male offspring rats were randomly selected at each group and fed with diets correspondent to their parents＇ for 70 days. The effects of exposure to TT52 on male reproductive system of offspring rats were assessed through sperm parameters, testicular function enzyme activities, serum hormones （FSH, LH, and testosterone levels）, testis histopathological examination, and the relative expression levels of selected genes along the hypothalamic-pituitary- testicular （HPT） axis. Results No significant differences were observed in body weight, food intake, organ/body weights, serum hormone, sperm parameters, testis function enzyme ACP, LDH, and SDH activities, testis histopathological changes, and relative mRNA expression levels of GnRH-R, FSH-R, LH-R, and AR along the HPT axis. Conclusion The results of this study demonstrate that parental dietary exposure to TT51 reveals no significant differences on the reproductive system of male offspring rats compared with MingHui63 and control.

Ovarian Toxicity and Epigenetic Mechanisms of Phthalates and Their Metabolites

Ovary plays an important role in the female reproductive system.The maintenance and regulation of ovarian function are affected by various physical and chemical factors.With the development of industrialization,environmental pollutants have caused great harm to public health.Phthalates,as a class of endocrine-disrupting chemicals(EDCs),are synthesized and used in large quantities as plasticizers due to their chemical properties.They are easily released into environment because of their noncovalent interactions with substances,causing human exposure and possibly impairing ovary.In recent years,more and more attention has been paid to the role of epigenetics in the occurrence and development of diseases.And it is urgent to study the role of methylation,gene imprinting,miRNA,and other epigenetic mechanisms in reproductive toxicology.

Research progress on the effects of phthalates on reproductive health of childbearing population and their offspring

The total fertility rate of women in childbearing age showed a downward trend in China.In addition to the age and genetic factors,environmental endocrine disruption can also impair fertility.The impact of increasing new environmental pollutants on the couples in childbearing age has become a research hotspot recently.Phthalate acid esters(PAEs)is a common plasticizer in plastic products,which is widely found in toys,food packaging,construction materials,electronic and medical components,personal care products,office and school supplies and other plastic packaging products,and is the main substance of environmental pollution.Multiple studies have shown that PAEs can not only cause environmental and water pollution,but also have a variety of toxic effects such as reproductive toxicity,genotoxicity,immunotoxicity,neurotoxicity,teratogenicity,and carcinogenesis.Therefore,its impact on human health,especially on reproductive health of people of reproductive age and their offspring,cannot be ignored.However,the current epidemiological study of PAEs and new alternatives in reproductive health population is still controversial,and the toxicity mechanism is still in the exploration stage.This article through to PAEs of parental generation,children(including embryo)of reproductive development and the influence of genetic toxicity research progress at home and abroad to do a review,aims to promote effective control measures for the establishment of PAEs pollutants rather than on reproductive health risk prediction,thus for PAEs of adverse reproductive outcomes of reproductive stage of people provide a scientific basis for precision control and guidance.

Long-term exposure to aryl hydrocarbon receptor agonist neburon induces reproductive toxicity in male zebrafish(Danio rerio)

Neburon is a phenylurea herbicide that is widely used worldwide,but its toxicity is poorly studied.In our previous study,we found that neburon has strong aryl hydrocarbon receptor(AhR)agonist activity,but whether it causes reproductive toxicity is not clear.In the present study,zebrafish were conducted as a model organism to evaluate whether environmental concentrations of neburon(0.1,1 and 10μg/L)induce reproductive disorder in males.After exposure to neburon for 150 days from embryo to adult,that the average spawning egg number in high concentration group was 106.40,which was significantly lower than 193.00in control group.This result was mainly due to the abnormal male reproductive behavior caused by abnormal transcription of genes associated with reproductive behavior in the brain,such as secretogranin-2a.The proportions of spermatozoa in the medium and high concentration groups were 82.40%and 83.84%,respectively,which were significantly lower than 89.45%in control group.This result was mainly caused by hormonal disturbances and an increased proportion of apoptotic cells.The hormonal disruption was due to the significant changes in the transcription levels of key genes in the hypothalamus-pituitary-gonadal axis following neburon treatment.Neburon treatment also significantly activated the AhR signaling pathway,causing oxidative stress damage and eventually leading to a significant increase in apoptosis in the exposed group.Together,these data filled the currently more vacant profile of neburon toxicity and might provide information to assess the ecotoxicity of neburon on male reproduction at environmentally relevant concentrations.

Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice

Microplastics(MPs)and nanoplastics(NPs)have become hazardous materials due to the massive amount of plastic waste and disposable masks,but their specific health effects remain uncertain.In this study,fluorescence-labeled polystyrene NPs(PS-NPs)were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo.Interestingly,whole-body imaging found that PS-NPs accumulated in the testes of mice.Therefore,the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice,and their mechanisms,were investigated.After oral exposure to PS-NPs,their spermatogenesis was affected and the spermatogenic cells were damaged.The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing(RNA-seq)to determine the toxic mechanisms;a ferroptosis pathway was found after PS-NP exposure.The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1(Fer-1),and it was also found that nuclear factor erythroid 2-related factor 2(Nrf2)played an important role in spermatogenic cell ferroptosis induced by PS-NPs.Finally,it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity.This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

菟丝子黄酮减轻雷公藤多苷生殖毒性的代谢组学分析

探究菟丝子黄酮干预雷公藤多苷生殖毒性的作用机制。随机将21只4周龄雄性大鼠分为正常组、雷公藤多苷组、菟丝子黄酮组,每组7只,连续灌胃12周。HE染色观察大鼠睾丸、附睾组织病理改变;采用超高效液相色谱-串联四级杆飞行时间质谱联用技术建立大鼠睾丸组织代谢指纹图谱,通过主成分分析、正交偏最小二乘判别分析筛选菟丝子黄酮干预生殖损伤模型大鼠的睾丸组织潜在生物标志物,并应用Metabo Analyst平台进行代谢通路分析。结果表明与雷公藤多苷组相比,菟丝子黄酮组各级精原细胞显著增加,生精小管排列更为规则。通过代谢组学技术共获得1-亚麻酰甘油磷酸胆碱、溶血磷脂、磷脂酰乙醇胺等47个差异代谢物,主要涉及苯丙氨酸、酪氨酸和色氨酸生物合成及代谢、鞘脂代谢、甘油磷脂代谢途径。本研究为菟丝子黄酮减轻雷公藤多苷所致生殖损伤提供科学依据。

饮用水消毒副产物暴露对女(雌)性生殖健康影响的研究进展

消毒副产物(disinfection byproducts,DBPs)是饮用水在消毒过程中消毒剂与原水中的有机前体物或无机物发生反应而产生的一类与消毒目的无关的污染物。目前,在已鉴定的DBPs中,三卤甲烷类和卤代乙酸类的含量和检出频率通常最高,并可通过饮水、洗澡与游泳等日常用水活动进入人体。DBPs作为一类广泛存在于饮用水中并具有潜在健康高风险的污染物,其对女性生殖健康的影响值得关注。本文综述了DBPs暴露对女(雌)性生殖健康的影响以及其可能的作用机制,并对今后相关研究方向进行了展望,以期为DBPs的女(雌)性生殖健康风险评估与饮用水卫生标准的修订工作提供参考依据。

Cyclophosphamide-induced reproductive toxicity: Beneficial effects of Helichrysum odoratissimum(Asteraceae) in male Wistar rats

Objective: Cyclophosphamide(CP) is commonly used to treat some cancers, but its clinical efficacy is also linked with testicular toxicity. We investigated the effects of aqueous extract(AE) and methanolic extract(ME) of Helichrysum odoratissimum for reducing CP-induced reproductive toxicity in male rats.Methods: In addition to a normal control(group 1), drugs or vehicles were administered orally to seven groups(n = 5) of rats that had already received 4-weeks of pre-treatment with CP(5 mg/[kgád], per oral administration);group 2 received CP + distilled water(10 m L/[kgád]);group 3 received CP + 5% tween 80(10 m L/[kgád]);group 4 received CP + clomiphene citrate(0.25 mg/[kgád]);groups 5 and 6 received CP + AE(50 and 100 mg/[kgád]) and groups 7 and 8 received CP + ME(50 and 100 mg/[kgád]). Animals were sacrificed on day 15, and body and sexual organ weights, sperm characteristics, testosterone level and testicular histology were evaluated.Results: The CP-treated group showed a significant reduction(P < 0.001) in the body and seminal vesicle weights, testosterone level, sperm count, sperm motility and sperm viability, but elevated(P < 0.001)sperm morphological abnormalities and testicular structure alterations, compared to the control group.Interestingly, these detrimental effects of CP were reversed by treatment with H. odoratissimum extracts.For instance, both extracts and all doses of H. odoratissimum significantly increased the sperm count(P < 0.001), sperm motility(AE, 50 mg/kg, P < 0.05;ME, 50 and 100 mg/kg, P < 0.05) and sperm viability(AE, 50 mg/kg, P < 0.001;ME, 50 and 100 mg/kg, P < 0.001) compared to the CP group. H. odoratissimum also improved plasmatic and intratesticular testosterone levels and prevented histological alterations of the testes.Conclusion: H. odoratissimum might be considered as an alternative drug to alleviate/prevent reproductive damage in cancer patients receiving CP chemotherapy.

The reproductive toxicity of saponins isolated from Cortex Albiziae in female mice

Saponin frsom Cortex Albiziae(SCA) are extensively used in the clinical treatment of tumor and depression. However, SCA may cause several adverse effects, including reproductive toxicity. The present study was designed to assess the mechanism by which SCA cause reproductive toxicity in female mice. The general reproductive toxicity testing was accomplished in female Kunming mice. The animals were divided into four groups: three groups that were treated by oral gavage with 135, 270, and 540 mg·kg-1·d-1 of SCA prepared in physiological saline, respectively, and one vehicle control group that was treated with physiological saline only. The gestational toxicity tests were conducted at 540 mg·kg-1·d-1. The general reproductive toxicity results showed that the pregnancy rate of the SCA-treated group decreased with the pregnancy rate being decreased by 70% at 540 mg·kg-1·d-1. SCA elicited maternal toxicity in the ovary and the uterus, but no fetal toxicity or teratogenicity was observed. The rates of implantation in the early, middle, and late pregnancy were all decreased, with stillbirths and maternal deaths being observed. Histopathological changes showed that SCA adversely affected the ovary and the uterus. In conclusion, SCA-induced reproductive toxicity in female mice is most likely caused by its damage to the ovary and the uterus.

Sertraline-induced reproductive toxicity in male rats： evaluation of possible underlying mechanisms

This study was conducted to clarify the toxic effects of sertraline （SRT） on the reproductive system of male rats and to elucidate the underlying mechanisms. Rats were treated orally with SRT at doses of 5, 10, and 20 mg kg-1 for 28 consecutive days. At the end of the treatment period, sperm concentration, sperm motility, and sperm morphology were investigated by computer-assisted sperm analysis system whereas sperm DNA damage was detected by comet assay. The oxidative status of the testes was investigated, and a histopathological examination was conducted. Serum testosterone, follicle-stimulating hormone （FSH）, and luteinizing hormone （LH） levels were measured to determine the effects of SRT on the spermatogenesis process. One-way ANOVA, post-hoc Dunnett＇s T3 test for the sperm comet assay, and post-hoc Tukey＇s test for the others were performed for statistical analysis. The results showed that SRT caused an increase in sperm DNA damage and induced histopathological lesions in all groups treated with SRT. There was abnormal sperm morphology and increased malondialdehyde （MDA） in the 10 mg kg-1 treatment group. More dramatic changes were observed in the 20 mg kg-1 treatment group. Decreased sperm count was accompanied by a significant increase in abnormal sperm morphology, DNA damage, and degeneration in cellular-tubular structures. Serum LH and testosterone levels were elevated in the 20 mg kg-~ treatment group. Decreased glutathione （GSH） and increased MDA were signs of enhanced oxidative stress （OS）. In conclusion, SRT induced testicular toxicity in a dose-dependent manner and OS is suggested as a crucial mechanism.

The antiestrogen-like activity and reproductive toxicity of 2,6-DCBQ on female zebrafish upon sub-chronic exposure

2,6-Dichloro-1,4-benzoquinone(2,6-DCBQ), an emerging water disinfection by-product, is widely detected in water resources. However, its potential effects on the reproductive system are largely unknown. Here, we investigated the long-term effects of 2,6-DCBQ on gonadal development by exposing zebrafish from 15 to 180 days postfertilization(dpf). Following exposure to 2,6-DCBQ(20 and 100 μg/L), female-specific effects including delayed puberty onset, retarded ovarian growth and breakdown of the zona radiata were observed, resulting in subfertility in adult females. Adverse effects in folliculogenesis disappeared two months after cessation of 2,6-DCBQ administration. In contrast, no adverse impacts were noted in male testes. The effects on females were associated with significant reduction in 17 β-estradiol(E2) level, suggesting a role for 2,6-DCBQ in anti-estrogenic activity. E2 level change in blood was further supported by dysregulated expression of genes( cyp19a1a, fshb, kiss3, esr2b, vtg1, and vtg3) related to the hypothalamic-pituitary-gonad-liver(HPGL) axis. The present study demonstrates for the first time that 2,6-DCBQ induces reproductive impairments in female zebrafish through disrupting 17 β-estradiol level.