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.

An Overview on Biological Markers in Reproductive and Developmental Toxicology: Concepts, Definitions and Use in Risk Assessment

Reproduction and development are complex couple-dependent processes. Risk assessment for these health outcomes requires the use of biomarkers to link exposures to disease. Biological markers of susceptability, external dose, internal dose, biologically effective dose, early or late biological responses, altered reproductive or developmental function, and reproductive or developmental disease are introduced. Using these biomarkers it is possible to define a biologically based risk assessment methodology for reproductive and developmental toxicity. Risk assessment for reproductive toxicity requires definition of male and female fecundity, couple-specific factors, spontaneous abortion, rate, and other factors. Using using sperm count as a biomarker for male fecundity, an example of a reproductive risk assessment using biomarkers is performed.

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 Toxicity in Mice Following Paternal Exposure to Di-N-Butyl-Phthalate (DBP)

Objective The aim of the present study was to investigate the effects of paternal Di‐N‐butyl‐phthalate （DBP） exposure pre‐ and postnatally on F1 generation offspring,and prenatally on F2 generation offspring.Methods Male mice were exposed to either 500 mg/kg or 2 000 mg/kg of DBP for 8 weeks,and mated with non‐exposed females.Three‐quarters of the females were sacrificed a day prior to parturition,and examined for the number of living and dead implantations,and incidence of gross malformations.Pups from the remaining females were assessed for developmental markers,growth parameters,as well as sperm quantity and quality.Results There were no changes in the fertility of parents and in intrauterine development of the offspring.Pups of DBP‐exposed males demonstrated growth‐retardation.Following paternal exposure to 500 mg/kg bw of DBP,there were almost twice the number of males than females born in the F1 generation.F1 generation females had a 2.5‐day delay in vaginal opening.Paternal exposure to 2 000 mg/kg bw of DBP increased the incidence of sperm head malformations in F1 generation males;however,there were no changes in the fertility and viability of foetuses in the F2 generation.Conclusion Paternal DBP exposure may disturb the sex ratio of the offspring,delay female sexual maturation,and deteriorate the sperm quality of F1 generation males.

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.

Assay for the developmental toxicity of safflower (Carthamus tinctorius L.) to zebrafish embryos/larvae

Objective:To explore the developmental toxicity and the potential toxicological mechanism of safflower (Carthamus tinctorius L.) on zebrafish embryos/larvae.Methods:Mortality,malformations and increased apoptosis induced by safflower were assessed in zebraflsh embryos from 6 to 96 hours post-fertilization.Enzymes and genes in the anti-oxidative and apoptotic pathways were also assayed.Results:The lethal concentration 50 of safflower to zebrafish embryos was 345.6 mg/L.Hatching inhibition,abnormal spontaneous movement,depressed heart rate,pericardial edema,yolk sac edema,abnormal head-trunk angle,inhibition of melanin release,enlarged yolk,and short body length were observed in safflower-treated zebrafish.Additional apoptotic cells mainly appeared around the heart.Safflower exposure changed the activities of defense enzymes (SOD T,CAT↑,MDA↑,GPX without trend),increased MDA content,decreased caspase-3 activity,and altered mRNA levels of related genes (ogg1 ↓,p53↓,Cu/Zn-sod↑,Mn-sod↓,cat↓,gpx↑).Conclusion:Safflower exhibits developmental toxicity for zebrafish embryos/larvae.The developing heart was speculated as the target organ of toxicity.Oxidative stress and increased apoptosis have roles in the developmental toxicity of safflower.This article provides a novel method to research the teratogenicity and possible mechanisms of toxicity of traditional Chinese medicines that are prohibited or contraindicated in pregnant women.

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.

EcR/USP-1-mediated ecdysteroid signaling regulates wolf spider(Pardosa pseudoannulata) development and reproduction

Lycosidae females demonstrate meticulous maternal care of offspring by carrying egg sacs and juvenile spiderlings during the reproductive stage. Nuclear receptors(NRs), especially the ecdysone receptor(EcR) and ultraspiracle(USP), have attracted considerable attention in the regulation of arthropod development and reproduction due to their pivotal roles in ecdysteroid signaling cascades. In the present study, 23 NRs, including one EcR and two USPs, were identified in the genome of the predatory wolf spider Pardosa pseudoannulata. RNA interference(RNAi) targeting EcR and USP-1inhibited spiderling development and resulted in nonviable eggs in the egg sacs. EcR and USP-1responded to changes in ecdysteroid levels, and interference in ecdysteroid biosynthesis led to similar phenotypes as ds EcR and ds USP-1 treatments.These findings suggest that EcR/USP-1-mediated ecdysteroid signaling regulates P. pseudoannulata development and reproduction. The P.pseudoannulata females with suppressed ecdysteroid signaling proactively consumed their non-viable egg sacs, resulting in a 7.19 d shorter first reproductive cycle than the controls. Termination of the failed reproductive cycle enabled the spiders to produce a new egg sac more rapidly. This reproductive strategy may partially rescue the reduction in population growth due to non-viable eggs and compensate for the physiological expenditure of wasted maternal care, which would be beneficial for the conservation of P.pseudoannulata populations and their natural control of insect pests.

Role of functional fatty acids in modulation of reproductive potential in livestock

Fatty acids are not only widely known as energy sources,but also play important roles in many metabolic pathways.The significance of fatty acids in modulating the reproductive potential of livestock has received greater recognition in recent years.Functional fatty acids and their metabolites improve follicular development,oocyte maturation and embryo development,as well as endometrial receptivity and placental vascular development,through enhancing energy supply and precursors for the synthesis of their productive hormones,such as steroid hormones and prosta-glandins.However,many studies are focused on the impacts of individual functional fatty acids in the reproductive cycle,lacking studies involved in deeper mechanisms and optimal fatty acid requirements for specific physiological stages.Therefore,an overall consideration of the combination and synergy of functional fatty acids and the establish-ment of optimal fatty acid requirement for specific stages is needed to improve reproductive potential in livestock.

Performance in Survival,Development and Reproduction of Aphis glycines Matsumura Virginoparae at High Temperatures

The soybean aphid,Aphis glycines Matsumura,is an important pest of soybean,which is native to Asia.In this study,A.glycines fed on soybean(AgFS)and A.glycines fed on wild soybean(AgFW)were reared at 25℃,27℃,29℃,31℃,33℃and 35℃,respectively,and some of the life parameters were determined.At temperature ranging from 25℃to 31℃,nymphs of AgFS and AgFW all developed into adults successfully.Only a few nymphs of AgFS and AgFW developed into adults at 33℃and no nymphs could develop into adults at 35℃.Lifespan,fecundity and body size of AgFS and AgFW adults all decreased gradually with temperatures increasing from 25℃to 33℃.At 25℃,the intrinsic rate of increase of AgFS was as big as that at 27℃,which was smaller than that at 29℃,but was bigger than that at 31℃.Intrinsic rate of increase of AgFW decreased gradually with temperatures increasing from 25℃to 31℃.Nymph stage duration of AgFW was longer than or as long as that of AgFS;adult lifespan of AgFW was shorter than or as long as that of AgFS.Adult fecundity,intrinsic rate of increase and adult body size of AgFW were all smaller than or as big as those of AgFS.It showed that AgFS and AgFW both survived and developed well at temperature ranging from 25℃to 31℃,and AgFW was more adaptive to low temperatures.These results were important to study the adaptability of A.glycines to high temperatures and for predicting its dynamics in the temperature keeping rising region.

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.

Preliminary Validation of Tumor Cell Attachment Inhibition Assay for Developmental Toxicants With Mouse S180 Cells

This study was designed to explore the possibility of using ascitic mouse sarcoma cell line (S180) to validate the mouse tumor cell attachment assay for developmental toxicants, and to test the inhibitory effects of various developmental toxicants. The results showed that 2 of 3 developmental toxicants under consideration, sodium pentobarbital and ethanol, significantly inhibited S180cells attachment to Concanavalin A-coaed surfaces. Inhibition was dependent on concentration, and the IC50 (the concentration tha reduced attachment by 50% ), of these 2 chemicals was 1.2×10-3mol/L and 1 .0 mol/L, respectively. Anoher developmental toxiant, hydmiortisone, did not show inhibitory activity. Two non-developmental toxicants, sodium chloride and glycine were also tested and these did not decrease attachment rates. The main results reported here were generally sindlar to those obtained with ascitic mouse ovdrian tumor cells as a model. Therefore, this study added further evidence to the conclusion that cell specificity does not lindt attachment inhibition to Con A-coated surfaces, so S180 cell may serve as an altemative cell model, especially when other cell lines are unavailable. Furthermore, after optimal validation, it can be suggested that an S180 cell attachment assay may be a candidate for a series of assays to detect developmental toxicants.

Prenatal amoxicillin exposure induces developmental toxicity in fetal mice and its characteristics

Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse outcomes.Currently,systematic studies about the developmental toxicity of amoxicillin are still lacking.We explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the midpregnancy.Meanwhile,PAmE altered multiple maternal/fetal serum phenotypes,especially in fetuses.Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>others.Further analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response relationship.In conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.

Identification and Expression Profile of a Neuropeptide LFRFamide-Like Gene During Different Stages of Gonadal Development in the Cephalopod Sepia pharaonis

Neuropeptides are widely distributed in vertebrates and invertebrates,regulating a variety of physiological activities in the organisms,such as metabolism,feeding and reproduction.In this study,to explore the function of neuropeptide LFRFamide in Sepia pharaonis,the full-length cDNA of LFRFamide-like gene(named SpLFRFL,MG869822.1)was identified with rapid amplification of cDNA ends(RACE)method.The sequence of SpLFRFL was 860 bp in length and encoded 188 amino acids containing 4 different mature peptides:1 copy of PHTPFRFamide,NSLFRFamide,TIFRFamide,and 3 copies of GNLFRFamide.Multiple alignment and phylogenetic analysis results showed that SpLFRFL shared high identity with LFRFamides of Sepia officinalis and Sepiella japonica and had the closest relationship with them.Through quantitative Real-time PCR(qRT-PCR),it was found that the SpLFRFL gene was highly expressed in the optic lobe and brain at three different stages during gonad development in both genders.Moreover,the four mature peptides at a concentration of 0.01μmol L^(−1) could inhibit the protein synthesis in the Chinese hamster ovary cell strain-K1(CHOK1)induced by SpGnRH.These data suggest that SpLFRFL might be involved in the development and reproduction of S.pharaonis.The results can contribute to future studies on neuropeptide evolution and function and benefit the cuttlefish farming.

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.

OsPPG encodes a pseudouridine-5'-phosphate glycosidase and regulates rice spikelet development

Florets are the basic structural units of spikelets,and their morphogenesis determines the yield and quality of rice grains.However,whether and how pseudouridine-5’-phosphate glycosidase participates in rice spikelet development remains an open question.In this study,we identified a novel gene,OsPPG,which encodes a peroxisome-localized pseudouridine-5’-phosphate glycosidase and regulates the development of rice spikelets.osppg mutants exhibited abnormal sterile lemma,lemma,palea,lodicule,stamens,and pistils;male sterility;shorter panicles;and reduced plant height.OsPPG was found to regulate several OsMADS genes,thereby affecting the morphogenesis of rice spikelets.Furthermore,metabolomics revealed that the OsPPG gene was involved in the decomposition of pseudouridine via the pyrimidine metabolism pathway and may affect the jasmonic acid signaling pathway.These results suggest that OsPPG is a key regulator of rice spikelet development.