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.

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.

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.

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.

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.

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 lithium on the survival,growth,and reproduction of Daphniopsis tibetana Sars(Crustacea:Cladocera)

We evaluated the effects of lithium on the survival, growth, and reproduction ofD. tibetana in the laboratory. The safe concentration value was 69.3 mg/L. The time to first brood was significant lower for individuals reared in 5 and 10 mg/L （24.4 and 24.0 d, respectively） compared with individuals reared in 20, 40, or 60 mg/L. Females reared in 5 mg/L lithium produced a mean of 16.5 neonates/brood and had the highest number of broods （3.0±1.95）. The rate of egg production （a）, the intrinsic rate of increase （rm）, net reproduction rate （R0）, and finite rate of increase （2） were highest for D. tibetana reared at 5 and 10 mg/L lithium, and the duration of development was shorter than for the remaining groups. The results indicated that rearing in 5 10 mg/L lithium can accelerate the growth and reproduction ofD. tibetana.

Effect of bis(tributyltin)oxide on reproduction and population growth rate of calanoid copepod Schmackeria poplesia

A full life-cycle toxicity test, combined with histology, on calanoid copepod Schmackeria poplesia was used to study the effect of bis（tributyltin） oxide （TBTO）. The results indicate no sex-specific differences in TBTO toxicity. Long-term mortalities of the copepods exposed to concentrations higher than 20 ng TBTO L＂1 were significantly elevated compared with that of control, and larval development was inhibited when they were exposed to 40 and 60 ng TBTO L-1. The percentages of ovigerous females were reduced compared with the control （P〈0.01） after 24 days exposure to concentrations higher than 10 ng TBTO L-1. Histological examinations suggest that exposure to TBTO might block the posterior end of the diverticula and inhibits the production of egg sacs. A modified Euler-Lotka equation was used to calculate a population-level endpoint, the intrinsic rate of natural increase （rm）, from individual life-table endpoints, i.e. mortality rate, time of release of first brood, sex ratio, the fraction of ovigerous females among all females as well as the number of nauplii per ovigerous female. Apart from the highest TBTO concentration （60 ng LI）, where all females aborted their egg sacs, 20 ng TBTO L-1 was the only concentration that significantly decreased rm compared with that of control （an effect associated with decreased sex ratio）. The results show that the S. poplesia is affected by prolonged exposure to low concentrations of TBTO. The full life-cycle toxicity test combined with histology experiments provides more integral understanding of the toxicity of endocrine disrupters.

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.

血清胸腺因子的大鼠围产期毒性试验研究

目的:观察血清胸腺因子对大鼠妊娠晚期、分娩期、哺乳期及胚胎和胎仔出生后生长发育、学习能力以及生殖能力的影响。方法:选择交配后的雌性SD大鼠,每组20只,从妊娠第15天至哺乳期结束,分别按0.88、1.75和3.50 mg/kg连续皮下注射给予血清胸腺因子,同时设0.9%氯化钠注射液为溶剂对照组,定期称取F0代雌鼠体质量、摄食量;F1代仔鼠确定出生存活率、哺乳期存活率,生理发育、新生反射达标天龄,训练学习、记忆能力,观察出生第12周后的仔鼠交配后的生殖行为,测定胚胎毒性各项指标。结果:注射血清胸腺因子后,溶剂对照组和受试药物各剂量组F0代妊娠鼠和哺乳鼠各周的平均体质量增长和摄食量正常,仔鼠总量、性别比和出生存活率(96.3%~97.9%)和哺乳期存活率(97.7%~98.9%)基本一致;F1代仔鼠的哺乳期和离乳后仔鼠平均体质量增长和摄食量基本正常。溶剂对照组仔鼠的生理发育和新生反射时间点检查项目均为正常达标天龄,游泳适应时间(28.5±15.8)s,空间定位建立时间(134.9±44.1)s,暗室电击反射建立时间(4.9±3.1)s,建立记忆电击次数1.7±0.9;F1代性成熟大鼠溶剂对照组的同笼交配率100%,妊娠率90%,平均着床数10.6±2.1,平均活胎数10.2±1.9,死胎数3,畸形胎数1;以上指标受试药物各剂量组间未见明显变化,与溶剂对照组比较,差异均无统计学意义(P>0.05)。结论:在本实验条件下,溶剂对照组与血清胸腺因子3个剂量组的大鼠妊娠后期个体及F1代胚胎及胎仔出生后生长发育、神经行为以及生殖能力等均未发现明显异常,未见围产期毒性反应。

刺山柑果风湿止痛凝胶膏对SD大鼠胚胎-胎仔发育的影响

目的:观察刺山柑果风湿止痛凝胶膏对SD大鼠胚胎-胎仔发育的影响。方法:实验设刺山柑果风湿止痛凝胶膏高(117.8 g/m^(2))、中(58.9 g/m^(2))、低(29.5 g/m^(2))剂量组,辅料对照组(辅料帖)和阳性对照组(环磷酰胺),妊娠第6天(GD6)~GD15每天经皮给药1次,阳性对照组于GD12皮下注射环磷酰胺。实验期间观察孕鼠的一般状况、体质量和饲料消耗量;GD20处死孕鼠,取胎仔,检查子宫连胎质量、黄体数、着床数、胎仔质量、胎仔身长、胎仔尾长、活胎数、死胎数、吸收胎数、胎仔性别及外观、内脏和骨骼畸形。结果:刺山柑果风湿止痛凝胶膏各剂量组孕鼠体质量、体质量增量、摄食量、子宫连胎质量、子宫和卵巢的脏器质量及其系数、平均黄体数、着床前丢失率、平均着床数、着床率、平均活胎数、活胎率、死胎率、吸收胎率、胎仔性别比、胎仔的外观异常率、窝均体质量、窝均身长、窝均尾长、骨骼畸形率和内脏畸形率与辅料对照组相比差异均无统计学意义(均为P>0.05)。结论:刺山柑果风湿止痛凝胶膏对SD大鼠胚胎-胎仔发育毒性的未见不良反应水平为117.8 g/m^(2),是临床拟用体表剂量的12倍。在本试验条件下,SD大鼠经皮给予刺山柑果风湿止痛凝胶膏对胚胎-胎仔发育无毒性影响。

长期摄入水解单宁对鼠类生殖的影响

水解单宁(hydrolyzed tannin)是橡子内主要的单宁酸类型,对以橡子为主要食物来源的鼠类的生存繁衍有重要影响.为探究长期取食水解单宁对鼠类的生殖激素与生殖器官产生的影响.选择72只(雌雄个体各36只)4周龄的健康昆明小鼠,随机分为4组,分别为对照组(水解单宁比例为0)、低单宁组(水解单宁比例为2%)、中单宁组(水解单宁比例为7%)和高单宁组(水解单宁比例为12%),用不同水解单宁含量的饲料饲喂42d后解剖取样.结果显示,高含量水解单宁显著降低了雄鼠存活率;中、高含量水解单宁对生殖激素的稳定产生负面效应;高含量水解单宁造成生殖器官损伤,导致小鼠卵巢与睾丸生理结构改变,降低了正常卵泡数量和精子的发生.试验验证了长期摄入高含量水解单宁打破了鼠类的生殖激素平衡且造成了生殖器官的损伤.

N-乙基吡啶溴对秀丽隐杆线虫生殖与脂代谢的多世代与跨世代效应

离子液体(ILs)的毒物兴奋效应(hormesis)使其低浓度、长期暴露的生态危害备受关注。本文以N-乙基吡啶溴([epyr]Br)作为ILs代表,以秀丽隐杆线虫为受试生物,开展连续多世代与跨世代生殖毒性效应研究,并从脂代谢酶、代谢中间产物探索其潜在机理。研究结果表明,在连续暴露的11代中,[epyr]Br在0.53 mg·L^(-1)水平对F1、F2、F3、F7、F8、F9和F10代线虫生殖产生刺激效应,在F6和F11中产生抑制效应;在53 mg·L^(-1)水平,在更多世代中表现出抑制效应,并且抑制水平比低浓度更强。跨世代效应中,[epyr]Br对F1脱离暴露的后代T3的生殖效应在高、低浓度均表现为抑制效应;同时,[epyr]Br在低浓度连续11代暴露后,对其脱离暴露的后代T3’的生殖依然表现出刺激效应;但[epyr]Br在高浓度多世代暴露后,对T3’无显著残留效应。在F1~F11代中,[epyr]Br对三酰基甘油(TG)、乙酰辅酶A(ACA)、磷酸甘油酰基转移酶(GPAT)、肉碱棕榈酰转移酶(CPT)等脂代谢物、代谢酶活性的多世代效应也表现为刺激、抑制效应的波动变化,各生化指标效应之间以及与生殖效应之间均存在密切关联,并存在高低浓度效应差异。在T3、T3’中,[epyr]Br对脂代谢物、脂代谢酶表现出显著的跨世代残留效应。综上,[epyr]Br连续多世代暴露的生殖毒性及其在脱离暴露后代中的残留效应,均与脂代谢密切相关,并受到暴露浓度的显著影响。

大豆异黄酮对幼年小鼠生殖发育的影响

目的探讨大豆异黄酮(SI)对幼鼠生殖发育的影响。方法将C57BL/6幼鼠随机分为对照组和SI小、大剂量组(10、100 mg/kg),每组10只,雌雄各半。各药物组幼鼠灌胃相应药液,每天1次,持续2周。末次灌胃后,计算幼鼠的体重增长百分比,检测血清雌二醇、睾酮水平以及生殖器官组织中丙二醛(MDA)含量、总抗氧化能力(T-AOC)和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,观察其生殖器官组织的病理改变,并检测其细胞凋亡情况。结果与对照组比较,SI大剂量组雌性幼鼠的体重增长百分比显著升高,而雄性幼鼠的体重增长百分比显著降低(P<0.05或P<0.01)。SI各剂量组幼鼠卵巢组织均可见囊性卵泡,睾丸组织可见精母细胞排列松散,附睾组织可见部分上皮细胞脱落。SI各剂量组雌性幼鼠血清睾酮水平和雄性幼鼠血清睾酮、雌二醇水平,SI小剂量组雌性幼鼠卵巢组织中GSH-Px活性和SI各剂量组雌性幼鼠卵巢组织中T-AOC,以及SI各剂量组雄性幼鼠睾丸及附睾组织细胞凋亡率均显著升高(P<0.05或P<0.01);SI各剂量组雌性幼鼠血清雌二醇水平,SI大剂量组雌性幼鼠卵巢组织中SOD活性和SI各剂量组雌性幼鼠卵巢组织中MDA含量,以及SI各剂量组雌性小鼠卵巢组织细胞凋亡率均显著降低(P<0.05或P<0.01)。结论SI可提高雌性幼鼠卵巢组织的抗氧化应激能力,减少其氧化应激损伤,但对雄性幼鼠的生殖器官具有一定的蓄积毒性。