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.

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.

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.

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.

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.

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.

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.

Protective effect of bone marrow mesenchymal stem cell-derived exosomes against the reproductive toxicity of cyclophosphamide is associated with the p38MAPK/ERK and AKT signaling pathways

Spermatogenic dysfunction caused by cyclophosphamide(CP)chemotherapy has seriously influenced the life quality of patients.Unfortunately,treatments for CP-induced testicular spermatogenic dysfunction are limited,and the molecular mechanisms are not fully understood.For the first time,here,we explored the effects of bone marrow mesenchymal stem cell-derived exosomes(BMSC-exos)on CP-induced testicular spermatogenic dysfunction in vitro and in vivo.BMSC-exos could be taken up by spermatogonia(GC1-spg cells).CP-injured GC1-spg cells and BMSC-exos were cocultured at various doses,and then,cell proliferation was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)assay.In addition,photophosphorylation of extracellular-regulated kinase(ERK),p38 mitogen-activated protein kinase(p38MAPK),and protein kinase B(AKT)proteins was evaluated by western blotting as well as apoptosis in GC1-spg cells measured using flow cytometry.Treatment with BMSC-exos enhanced cell proliferation and reduced apoptosis of CP-injured GCI-spg cells.Phosphorylated levels of ERK,AKT,and p38MAPK proteins were reduced in CP-injured spermatogonia when co-treated with BMSC-exos,indicating that BMSC-exos acted against the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways.In experiments in vivo,CP-treated rats received BMSC-exos by injection into the tail vein,and testis morphology was compared between treated and control groups.Histology showed that transfusion of BMSC-exos inhibited the pathological changes in CP-injured testes.Thus,BMSC-exos could counteract the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways.The findings provide a potential treatment for CP-induced male spermatogenic dysfunction using BMSC-exos.

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.

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.

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.

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.

The protective effect of vitamin E against oxidative damage caused by formaldehyde in the testes of adult rats

Aim： To investigate the effect of formaldehyde （FA） on testes and the protective effect of vitamin E （VE） against oxidative damage by FA in the testes of adult rats. Methods： Thirty rats were randomly divided into three groups： （1） control; （2） FA treatment group （FAt）; and （3） FAt ＋ VE group. FAt and FAt ＋ VE groups were exposed to FA by inhalation at a concentration of 10 mg/m^3 for 2 weeks. In addition, FAt ＋ VE group were orally administered VE during the 2-week FA treatment. After the treatment, the histopathological and biochemical changes in testes, as well as the quantity and quality of sperm, were observed. Results： The testicular weight, the quantity and quality of sperm, the activities of superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px） and glutathione （GSH） were significantly decreased whereas the level of malondialdehyde （MDA） was significantly increased in testes of rats in FAt group compared with those in the control group. VE treatment restored these parameters in FAt ＋ VE group. In addition, microscopy with hematoxylin-eosin （HE） staining showed that seminiferous tubules atrophied, seminiferous epithelial cells disintegrated and shed in rats in FAt group and VE treatment significantly improved the testicular structure in FAt ＋ VE group. Conclusion： FA destroys the testicular structure and function in adult rats by inducing oxidative stress, and this damage could be partially reversed by VE.

The Protective Effect of Ascorbic Acid and Thiamine Supplementation against Damage Caused by Lead in the Testes of Mice

Lead is a ubiquitous environmental and industrial pollutant that may have toxic effects on the male. Vitamins may protect against toxic effects of lead in the liver and reproductive system, which is confirmed by our initial research. The aim of this study was to further investigate the protective effects of vitamins （ascorbic acid combined with thiamine） on lead acetate （Pb）-induced reproductive toxicities in mice and study the possible mechanisms underlying these effects. Forty-five male mice were randomly divided into 3 groups, 15 mice in each and received daily intragastric administration with control, Pb （20 mg/kg）, and Pb＋vitamins （ascorbic acid of 420 mg/kg＋thiamine of 30 mg/kg） for 6 weeks, respectively. The Pb-treated animals showed significant decreases in the epididymal sperm count and motility compared to the control group, while the Pb＋vitamins group had significant increases for these variables. Moreover, an increasing apoptosis of germinal cells induced by Pb was reduced by vitamin treatment. Pb induced the activation of Caspase-3, Fas/Fas-L and Bcl-2 with elevated levels, and the adaptor protein primarily regulated signaling through Fas and required for Fas-induced apoptosis. In conclusion, ascorbic acid combined with thiamine exhibited protective effect on reproductive system by inhibiting Pb-induced excessive cell apoptosis.

Exposure to bifenthrin disrupts the development of testis in male Sebastiscus marmoratus

Bifenthrin（BF） is a pyrethroid insecticide that is widely used in agriculture, horticulture, and for residential purposes. However, few studies addressing the reproductive toxicity of BF on fishes are available. The present study was conducted to investigate the effects of BF on testicular development in Sebastiscus marmoratus and to gain insight into its mechanism. After exposure to 1, 10 and 100 ng/L BF for 50 days, there was a reduced number of mature sperm and an abundance of the late stages of spermatocysts in the testes. The levels of 17β-estradiol and testosterone were decreased significantly after BF exposure. The activity of caspase-3 was increased in a dosedependent manner after BF exposure, TUNEL assay indicated that BF exposure resulted in the occurrence of apoptosis in the testes, which might be main reason for the inhibition of spermatogenesis.

Studies on Mutagenicity and Teratogenicity of Sarafloxacin

Wistar rats and closed Kunming strain mice were selected to study the genetic toxicity of sarafloxacin. The results indicated that sarafloxacin had no significant toxic effect of an excreted mutagen in S. typhimurium strains, and did not induce significantly higher percentages of polychromatic erythrocytes with micronuclei (MNPCE) in mice. No significant mutagenic activity was observed in dominant lethal assay. At 5 and 50mg/kg b.w. , sarafloxacin did not produce significant effects on the reproductive parameters of litters and fetal growth, and did not induce the teratogenic effects on fetuses. Sarafloxacin induced some toxic effects on body length and skeletal growth in fetuses of 500mg/kg b.w., but had no significant dose - response relationship among the administered dosages of sarafloxacin. The results of the genetic toxicology above indicated that no evidence showing sarafloxacin was mutagenic and potentially teratogenic for animals.

Influence of Isoflurane Exposure for 15 Consecutive Days on Ovarian Function in Adult Female Mice

Female infertility after occupational exposure to inhaled anesthetic agents has attracted critical attention,but systematic studies focusing on the impact of inhaled anesthetics on the female reproductive system have not been well-established.We used a murine model to study the effect of isoflurane exposure on infertility in female adult mice and investigated the potential underlying mechanism.One hundred adult female C57 mice were randomly allocated into 5 groups exposed in air containing 0,2500,5000,10000 or 20000 ppm isoflurane for 15 consecutive days.Estrous cycle length was measured based on vaginal smear examination,ovarian histopathologic enumeration of follicles,and serum estradiol(E2),anti-Mullerian hormone(AMH),follicle-stimulating hormone(FSH),and luteinizing hormone(LH)levels to assess the effect of isoflurane on ovarian reserve.Compared to the control group,significant prolongation of the estrous cycle of the adult female mice was observed in the 20000 ppm isoflurane exposure group.Serum AMH was significantly decreased,and FSH and LH levels profoundly increased in the 5000,10000,and 20000 ppm isoflurane exposure groups compared to the control group.The histopathologic examination revealed a reduced number of developing follicles and an increased number of atretic follicles after isoflurane exposure,but the difference was not statistically significant.Thus,exposure to a higher concentration of isoflurane might have an adverse effect on ovarian reserve in sexually-mature female mice.

Security of a Novel Antitapeworm Drug:Arecoline Hydrobromide

[Objective] To make an objective evaluation about security of a new veterinary drug-arecoline hydrobromide according to the research results and papers in recent years and supply science basis for clinical usage. [ Method] The security of arecoline hydrobromide was evaluated based on acute toxicity tests; the ranges of safe medication, tolerability and toxicity as well as ＂Three-induced＇ effects （carcinogensis, mutagene- sis and teratogenesis） and reproductive toxicity were summarized according to the combinations of experimental results, papers and clinical effects. E Result] The results of acute toxicity tests in mice and rats showed that LD^0 （50% lethal dosages） of arecoline hydrobromide in mice was 691.83 mg/（kg.BW） and 95% incredible range of its LDso was 642.92 -744.47 mg/（ kg. BW）, and LDso of arecoline hydrobromide in rats was 2 054 mg/（kg.BW） and 95% incredible range of its LDso was 1 908 -2 210 mg/（kg.BW）. Its LDso value was hundreds times higher than the recommen- ded clinical dosage [ 1 -5 mg/（kg-BW） ], therefore it is safe to apply in clinic. The research results of ranges of safe medication, tolerability and toxicity showed that arecoline hydrobromide could entirely dispel the dog Diphyllobothrium, Spirometra mansoni, Dipylidium mesocestoides, Linea- tus and Cysticercus at dosages of 2 -3 mg/（ kg.BW）, and the same effects to Railletina tapeworm of chickens and Drepanidotaenia lanceolata of duck and goose at dosages of I -2 mg/（kg.BW）. The arecoline hydrobromide had muscarinic effects as side-effects and could cause vomiting, di- arrhea and other clinical symptoms to discharge the paralyzed worm from livestock body rapidly and completely. The arecoline hydrobromide had ＂Three-induced＂ effects and reproductive toxicity when it was used as antitapeworm drug with long-term, sustained and a large number of drug us- age, rather than used in clinical application with shorter time and lower dosage of administration. [ Conclusion] The arecoline hydrobromide is low- toxic substance and has a certain of toxicity such as ＂Three-induced＂ effects and reproductive toxicity at high-dosages application, and there are good effects on livestock and poultry tapeworm at the clinical recommended dosacles without ＂Three-induced＂ effects and reproductive toxicity.