Research progress on food-derived antioxidants for alleviating toxicity of endocrine disrupting chemicals / 环境与职业医学

Endocrine disrupting chemicals (EDCs) are a class of chemical substances widely present in daily-life environment, and can enter human body through various pathways, posing a threat to reproductive development and health. Oxidative stress (OS) is one of the most important fundamental mechanisms underlying the reproductive toxicity of EDCs. Numerous studies have found that exposure to EDCs can increase the levels of reactive oxygen species (ROS) in human reproductive system and reduce the activity and quantity of multiple enzymatic antioxidants, leading to oxidative stress and inducing damage to the reproductive system at various levels such as DNA and cells. Many research results have shown that supplementing food-derived non-enzymatic antioxidants can reduce ROS levels and increase the activity of enzymatic antioxidants, thereby reduce OS levels, and further repair EDCs-induced reproductive damage. In addition, many food-derived antioxidants are important elements involved in reproductive physiological activities and have protective effects on reproductive health. This paper summarized the reproductive toxicity of EDCs, including damage to reproductive cells, interference with hormone action, and influence on reproductive-related epigenetic regulation, elaborated the relationship between OS and reproductive toxicity of EDCs, and further summarized the alleviating effects and related mechanisms of food-derived antioxidants such as vitamins, trace elements, and plant polyphenols and pigments against reproductive toxicity of EDCs, aiming to provide a theoretical and scientific basis for prevention and treatment against reproductive toxicity of EDCs.

Research progress on effects of radio frequency radiation and its physical parameters on male reproductive system / 环境与职业医学

With the widespread use of mobile phones, laptops, and WIFI, the effects of radio frequency radiation (RFR) on human health are of increasing concern, and there are particular concerns about its reproductive toxicity. Studies have shown that the reproductive system is a sensitive target for RFR. In males, RFR is associated with decreased sperm quality and serum testosterone levels, but there are few studies on the biological effects of RFR by altering physical parameters on the male reproductive system. This paper introduced common sources of RFR, reviewed the toxic effects and mechanisms of RFR targeting male reproductive system from the aspects of spermatogenic cells, sperm structure, blood-testicular barrier, and testicular function, and analyzed male reproductive system related toxic effects of RFR by varying physical parameters including frequency, treatment duration, and specific absorption rate, so as to provide a theoretical basis and scientific basis for the safe and reasonable use of radio frequency electromagnetic field by humans and subsequent in-depth research.

Research progress on reproductive toxicity and reproductive system tumors induced by environmental endocrine disrupting chemicals / 环境与职业医学

Environmental endocrine disrupting chemicals are a kind of exogenous chemicals that generally exist in the environment, and can disturb the endocrine homeostasis and adversely affect reproductive, immune, neurological, and other functions after entering the body, among which the damage to the reproductive system is the most significant one. Studies have confirmed that the long-term exposure to environmental endocrine disrupting chemicals have irreversible and harmful effects on primordial germ cell growth, reproductive organ development, and reproductive endocrine regulation, and also have obvious correlations with the occurrence and development of various reproductive system tumors. This paper reviewed various reproductive toxicities induced by common environmental endocrine disrupting chemicals in the developmental and reproductive stages, and associated mechanisms involved in the occurrence and development of reproductive system tumors.

Reproductive toxicity and associated mechanism of tricresyl phosphate on Caenorhabditis elegans / 环境与职业医学

Background Tricresyl phosphate (TCP) is mainly used as a flame retardant. Studies have confirmed that it has cytotoxicity and neurotoxicity, but its reproductive toxicity is not clear. Objective To investigate the reproductive toxicity and potential mechanism of TCP subacute exposure on Caenorhabditis elegans. Methods Caenorhabditis elegans were exposed to solvent control and 0.1, 1, 10, 100, and 1000 μg·L−1 TCP respectively for 72 h. Brood size and number of fertilized eggs in the uterus were detected to evaluate reproductive ability. The number of total germline cells and the relative area of gonad arm were measured to evaluate the development of gonads. The body length and body width of Caenorhabditis elegans were detected to evaluate growth and development. The activities of reactive oxygen species (ROS) and superoxide dismutase (SOD) in Caenorhabditis elegans, and the mitochondrial active oxygen metabolism genes (mev-1 and gas-1) of N2 nematodes were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) to evaluate oxidative stress. WS1433 transgenic nematodes and wild-type nematodes N2 were exposed to solvent control or TCP (0.1, 1, 10, 100, and 1000 μg·L−1) respectively. DNA damage in germ cells of WS1433 transgenic nematodes was detected, the relative expressions of DNA damage-related genes (hus-1, clk-2, cep-1, and egl-1) in N2 nematodes were detected by qRT-PCR to evaluate the effect of TCP exposure on genetic damage. Results Compared with the solvent control group (217.00 ± 12.20), the brood size of N2 nematodes in the 100 μg·L−1 and 1000 μg·L−1 TCP groups decreased (170.80 ± 11.51, 169.60 ± 10.52, P < 0.05). Compared with the solvent control group (18.43 ± 1.69), the number of fertilized eggs of N2 nematodes in the 100 μg·L−1 and 1000 μg·L−1 TCP groups decreased (13.47 ± 0.81, 11.95 ± 0.90, P < 0.05). Compared with the solvent control group (312.46 ± 77.4), the number of total germline cells of N2 nematodes in the 100 μg·L−1 and 1000 μg·L−1 TCP groups decreased (281.80 ± 12.98, 273.50 ± 8.53, P < 0.05). Compared with the solvent control group, the relative area of gonads of N2 nematodes in the 100 μg·L−1 and 1000 μg·L−1 TCP groups decreased by 13.83% and 17.25% respectively (P<0.05). Compared with the solvent control group [(1058.10±80.12) μm, (78.21±14.69) μm], the body length and body width of N2 nematodes in the 100 μg·L−1 and 1000 μg·L−1 TCP groups decreased (P<0.05). Compared with the solvent control group, the relative fluorescence intensity of ROS in nematodes in the 10, 100, and 1000 μg·L−1 TCP groups increased significantly (107.60%±1.02%, 105.90%±1.40%, and 106.40%±1.85%, respectively, P<0.05), and the activities of SOD were reduced (by 20.66%, 15.88%, and 16.44%, respectively, P<0.05). Compared with the solvent control group (1.3±1.3), the number of DNA-damaged germ cells of WS1433 nematodes in the 100 and 1000 μg·L−1 TCP groups increased significantly (2.4±0.3, 2.7±0.3, P<0.05); the expressions of mev-1 and gas-1 genes in N2 nematodes in the 10, 100 and 1000 μg·L−1 TCP groups decreased significantly (P<0.05); the expressions of hus-1 in the 0.1-1000 μg·L−1 TCP groups significantly increased (P<0.05); the expressions of clk-2 and egl-1 in the 100 and 1000 μg·L−1 TCP groups increased significantly (P<0.05); the expressions of cep-1 in the 1, 10, and 100 μg·L−1 TCP groups increased significantly (P<0.05). Conclusion TCP may cause reproductive damage to nematodes through oxidative stress and germ cell DNA damage.

Protective effect of Lycium barbarum polysaccharide on reproductive system injury of female rats induced by 2,4-dichlorophenoxyacetic acid / 环境与职业医学

Background 2,4-Dichlorophenoxyacetic acid (2,4-D) is widely used as a broad-leaved herbicide and plant growth regulator. Related studies have shown that 2,4-D has neurotoxicity, ability to disrupt endocrine function, genotoxicity, carcinogenicity, and reproductive toxicity. Objective This experiment is conducted to investigate the effect of 2,4-D exposure on reproductive system of female rats, and to preliminarily explore the potential ameliorative effect of Lycium barbarum polysaccharide (LBP) and its possible mechanism. Methods Twenty-four SPF female SD rats with six rats in each group were randomly divided into a blank control group (deionized water 1 mL·d−1), an exposure group (75 mg·kg−1 2,4-D), an LBP control group (50 mg·kg−1 LBP), and an LBP intervention group (75 mg·kg−1 2,4-D + 50 mg·kg−1 LBP). The rats were given intragastric administration once a day for 28 consecutive days. Body weight was measured every two days. After exposure, ovary and uterus were weighed and organ coefficients were calculated; the pathological changes of ovary and uterus were detected by hematoxylin-eosin staining (HE); the level of estradiol (E2) in serum was detected by ELISA; the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) in serum were measured by corresponding kits; the apoptosis of ovarian and uterine cells was detected by TUNEL fluorescence staining; and the protein expression levels of Fas, FasL, FADD, Pro-Caspase-8, Cleaved-Caspase-8, Pro-Caspase-3, and Cleaved-Caspase-3 in ovarian tissues were detected by Western blotting. Results Compared with the blank control group, the ovarian structure of the exposure group was abnormal, the number of follicles at different developmental stages decreased, morphological changes were observed, and the number of atretic follicles increased; the endometrium was incomplete, with different degrees of nuclear pseudostratification and decreased number of glands in lamina propria. Compared with the exposure group, the ovarian structure of the LBP intervention group was complete, and the follicles at different developmental stages increased in amount, remained intact, and were arranged closely; the uterine structure was relatively intact, showing decreased endometrial loss and nuclear pseudostratification. There were significant differences in the levels of SOD, GSH-Px, E2, and MDA among the four groups (F=86.1, 26.2, 43.3, and 22.3, all P<0.01). Compared with the blank control group, the levels of serum SOD, GSH-Px, and E2 decreased in the exposure group (P<0.01), while the concentration of MDA increased (P<0.01). Compared with the exposure group, the levels of serum SOD, GSH-Px, and E2 in the LBP intervention group increased (P<0.01), and the concentration of MDA decreased (P<0.01). There were significant differences in the apoptosis rates of ovarian and uterine cells among the four groups (F=64.8, 55.5, both P<0.01). Compared with the blank control group, the apoptosis rates of ovarian and uterine cells increased in the exposure group (P<0.01). Compared with the exposure group, the apoptosis rates of ovarian and uterine cells decreased in the LBP intervention group (P<0.01). There were significant differences in the expression levels of death receptor pathway-related proteins in ovarian tissues among the four groups (all P<0.05). Compared with the blank control group, the expression levels of Fas, FasL, FADD, Pro-Caspase-8, Cleaved-Caspase-8, Pro-caspase-3, and Cleaved-Caspase-3 were increased in the exposure group (P<0.05 or 0.01). Compared with the exposure group, the expression levels of above proteins were decreased in the LBP intervention group (P<0.05 or 0.01). Conclusion The study findings reveal that 2,4-D can induce oxidative stress and further mediate Fas-FasL pathway to induce apoptosis, resulting in reproductive system damage in female rats. LBP can reduce the oxidative stress level, down-regulate the expression of Fas-FasL pathway-related proteins, and reduce the apoptosis of germ cells, therefore protecting reproductive system of female rats.

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 / 亚洲男科学杂志(英文版)

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.

Research progress on the exposure pathway and toxic effect of microplastics / 中国职业医学

Global plastics production has been increasing year by year. Due to the large quantity of plastics and the difficulty of their degradation, plastics are continuously accumulated in the environment. Therefore, plastic waste has become one of the most serious threats to the global environment. Microplastics can be absorbed into organisms through the mouth, respiratory tract and skin, causing organ(intestine, liver) toxicity, reproductive and developmental toxicity, and neurotoxicity. Moreover, microplastics can also take up other pollutants distributed in the surrounding environment, such as heavy metals and organic pollutants, jointly exerting combined toxic effects. The extracts of microplastics, including microplastics unstable polymers and additives, also have toxic effects. The molecular mechanisms involved in the toxic effects induced by microplastics include oxidative stress, inflammation, disturbance of intestinal flora, disturbance of gene expression, and others.

Acrylamide Toxicity and Mitigation Strategies: A Summary of Recent Reports

Acrylamide is a potential carcinogen, with proven neurotoxicity and genotoxicity. In the current scenario, neurotoxicity and reproductive toxicity of acrylamide have not been conclusively established for humans; however, the same has been established in laboratory animal species. In this review, we summarize the factors dictating the exposure of acrylamide to humans and subsequently caused toxicity to humans. Further, we review the neurotoxic and genotoxic effects of acrylamide on animal models, with a particular emphasis on reproductive toxicity. We also talk about various strategies such as physical, chemical, and biological approaches, employed for acrylamide. Overall, we discuss that consumption of acrylamide through food products has toxic effects on the endocrine system, and it is deleterious for human health. A novel aspect of this review is that we provide a molecular mechanism of action in conjunction with clinical data on acrylamide toxicity along with relevant examples. This review also highlights the requirement of further research on the consequences of acrylamide toxicity, molecular modes of action, and the overall impact on the human body

Two-generation reproductive toxicity of lufenuron in SD rats / 中国职业医学

OBJECTIVE: To obtain information on the toxicity of lufenuron on the reproduction ability and the growth and development of offspring in female and male rats through two-generation reproduction toxicity study. METHODS: The specific pathogen free healthy SD rats were randomly divided into control group and low-, medium-and high-dose lufenuron groups, with 60 rats in each group, half females and half males. Rats in the low-, medium-and high-dose lufenuron groups were respectively fed with lufenuron at the dose of 5.0, 20.0 and 80.0 mg/(kg body weight·day) for 8 weeks before mating. The control group was fed with standard foot. The reproductive index, brain and reproductive organ coefficients and pathological changes were observed in P and F1 parents. The birth and growth indexes of the offspring were measured. RESULTS: i) P generation: from the 14 th day, the female rats in the medium-dose group had lower body weight than that of the female control group(P<0.05); from the 35 th day, the body weight was lower than that of the female low-dose group(P<0.05). From the 14 th day, the female rats in the high-dose group had lower body weight than that of the other three female groups(P<0.05). From the 14 th day, the male rats in the medium-and high-dose groups had lower body weight than that of the male control group and low-dose group(P<0.05). The body weight of pregnant rats in the parental high-dose group was lower than that of the control group, low-dose group, and medium-dose group at day 0, 7, 14, 19 of the pregnancy duration(P<0.05). The body weight of pregnant rats in the parental medium-dose group was lower than that of the low-dose group on day 0 of the pregnancy duration, and lower than that of the control and low-dose groups on day 7 and 14(P<0.05). The conception rate, the new-borne survival rates and the feeding survival rate of female rats in the high-dose group was lower than that of the other three female groups(P<0.008). The new-borne feeding survival rate of female rats in the medium-dose group was lower than that of the control group and low-dose group(P<0.008). The organ coefficients of brain in female rats in the medium-and high-dose groups were higher than that of the female control group and low-dose group(P<0.05). The organ coefficients of brain and testis in male rats in the medium-and high-dose groups were higher than that of the control group and low-dose group(P<0.05). The organ coefficient of epididymis in male rats in the high dose group was lower than that of the other three male groups(P<0.05). ii) F1 generation: the body weight of female rats in the low-and medium-dose group was higher than that of the female control group on the 42 th day(P<0.05). The body weight of male rats in the low-dose group was higher than that of the male control group on the 42 th, 49 th, and 56 th days(P<0.05). The body weight of male rats in the medium-dose group was higher than that of the male control group on the 14 th, 21 th, 42 th, 49 th, and 56 th days(P<0.05). The new-borne survival rate in the low-dose group was lower than that of the control group(P<0.017). The body weight of new-borne rats in the high-dose group on day 4 of birth was lower than that in the other three female groups(P<0.05). iii) F2 generation: the body weight of male rats in the male medium-dose group was lower than that in the control group on day 21 of birth(P<0.05). CONCLUSION: The reproductive and developmental toxicity of lufenuron is found in rats in the medium-and high-dose groups. Toxicities including low body weight, conception rate, new-borne survival rate and feeding survival rate are found in P generation; low body weight and feeding survival rate are found in F1 generation; low body weight is found in male F2 generation. The no-observed-adverse-effects levels of lufenuron in two-generation reproductive study are 5.87 mg/(kg·d) for females and 5.09 mg/(kg·d) for males in SD rats.

Study on Toxic Effect of the Extract from Tripterygium hypoglaucum on Embryo-fetal Development of New Zealand Rabbits / 中国药房

OBJECTIVE：To study the toxic effect of the extract from Tripterygium hypoglaucum on pregnant animal and embryo-fetal development . METHODS ：Successfully mated New Zealand female rabbits were randomly divided into solvent control group，positive control group （cyclophosphamide，20 mg/kg）and T. hypoglaucum extract high-dose ，medium-dose and low- dose groups（15.0，7.50，3.75 g/kg，by the amount of crude drug ）according to their body weight ，with 18 rabbits in each group at least. The female rabbits in solvent control group and T. hypoglaucum extract groups were given water or the corresponding T. hypoglaucum extract solution from 6th to 18th day of pregnancy ，5 mL/kg，once a day. Positive control group was given cyclophosphamide subcutaneously into the neck from 10th to 13th day of pregnancy ，1 mL/kg，once a day. According to the related requirements of Technical Guidelines for the Study of Drug Reproductive Toxicity ，the general situation ，body weight ，body weight increase and food intake of female rabbits were observed and recorded during the experiment ，and euthanasia was carried out on 28th day of pregnancy ；the relative indexes of main organs ，fetal uterus ，placenta uterus ，placenta，ovary，implantation gland ， absorption fetus ，stillbirth，live fetus and corpus luteum were observed and recorded after anatomy ；the relative indexes of body weight，appearance，visceral and skeletal alterations of the fetus were detected . RESULTS ：Compared with solvent control group ， the body weight ，body weight increase ，food intake ，main organs ，pregnancy of pregnant rabbits ，as well as reproductive function，embryo formation ，fetal growth and development ，appearance，visceral and skeletal development indexes in T. hypoglaucum extract groups had no significant abnormal changes （P＞0.05）；above indexes in the positive control group had significant changes （P＜0.05），and significant maternal toxicity and embryotoxicity were found. CONCLUSIONS ：T. hypoglaucum extract 15.00-3.75 g/kg（by the amount of crude drug ）have no significant maternal toxicity ，embryotoxicity or fetal development toxicity to New Zealand rabbits.

Effect Of Environmental Toxicity On Reproductive System: A Review

Reproductive toxicity is the toxicity of reproductive system caused due to environmental factors such as chemicals, heavy metals etc. They interfere in some way with normal reproduction, such substances are called reprotoxic. It includes hazardous effects on fertility and sexual function in adult males and females as well as developmental toxicity in the offspring. Developmental toxicity is abnormal structure or functional development following exposure of pregnant or lactating females. In environment there are various factors which are responsible for causing adverse effect on reproductive system. Heavy metals like cadmium, lead, mercury, Industrial chemicals like phthalates, BPA, Agricultural chemicals, radiations, some of the narcotics drugs like morphine, ethanol, psychotropic drugs like diazepam, chlorpromazine, hypotensives like methyldopa, reserpine. All these factors acts as reproductive toxicants and affects male and female reproductive system causing spontaneous abortion, miscarriage, reduced fertility, preterm delivery, LBW, affect sertoli cells in the testis, affect leydig cell function etc. In ancient Ayurvedic texts also it is described that the heavy metal such as mercury, copper affects the reproductive system. Metals and metallic compounds, pesticides, some food additives have a nature of accumulations within the living body when it exposed since prolonged period. These factors accumulate in the body day by day. This is nothing but Dushivisha (cumulative toxins). Dushivishas vitiates the Dhatus after the laps of a long time on obtaining a favorable condition. It also affects the Shukradhatu causing Shukrashaya (diminish semen). People should be aware of all these factors to take adequate precaution.

Impact of subchronic exposure to low-dose nano-nickel oxide on the reproductive function and offspring of male rats / 中华男科学杂志

Objective@#To investigate the influence of subchronic exposure to low-dose subchronic nano-nickel oxide (NNO) on the reproductive function of male rats and embryonic development of the pregnant rats.@*METHODS@#Fifty normal healthy male SD rats weighing 180－220 g were randomly divided into five groups of equal number, negative control, 4 mg/ml micro-nickel oxide (MNO), and 0.16, 0.8 and 4 mg/ml NNO, those of the latter four groups exposed to MNO or NNO by non-contact intratracheal instillation once every 3 days for 60 days, and then all mated with normal adult female rats in the ratio of 1∶2. After the female animals were confirmed to be pregnant, the males were sacrificed and the weights of the body, testis and epididymis obtained, followed by calculation of the visceral coefficients, determination of epididymal sperm concentration and viability and the nickel contents in the blood and semen by atomic fluorescence spectrometry. The female rats were killed on the 20th day of gestation for counting of the implanted fertilized eggs and live, dead and resorbed fetuses.@*RESULTS@#After 60 days of exposure, the rats of the NNO groups showed no statistically significant differences from those of the negative control and MNO groups in the weights of the body, testis and epididymis or visceral coefficients. Compared with the negative control group, the animals of the 0.8 and 4 mg/ml NNO groups exhibited markedly decreased sperm concentration (［9.36 ± 0.98］ vs ［7.49 ± 1.46］ and ［6.30 ± 1.36］ ×10⁶/ml, P < 0.05) and viable sperm (［85.35 ± 9.16］% vs ［68.26 ± 16.63］% and ［65.88 ± 14.68］ %, P < 0.05), increased morphologically abnormal sperm (［8.30 ± 2.47］% vs ［13.99 ± 4.87］% and ［15.38 ± 8.86］ %, P < 0.05), and elevated rate of dead and resorbed fetuses (1.18% vs 6.89% and 7.37%, P < 0.05), blood nickel content (［0.13 ± 0.16］ vs ［0.52 ± 0.34］ and ［0.82 ± 0.44］ mg/L, P < 0.05) and semen nickel content (［0.08 ± 0.13］ vs ［0.35 ± 0.23］ and ［0.63 ± 0.61］ mg/L, P < 0.05). The nickel level in the semen was correlated significantly with that in the blood (r = 0.912, P <0.01), negatively with the rate of viable sperm (r = －0.879, P <0.01) and positively with the percentage of morphologically abnormal sperm (r = －0.898, P <0.01).@*CONCLUSIONS@#Sixty-day exposure to nano-nickel oxide at 0.8 and 4 mg/ml can produce reproductive toxicity in male rats and result in fetal abnormality in the females, while that at 0.16 mg/ml has no significant toxic effect on the reproductive function of the males.

Effect of bisphenol F, an analog of bisphenol A, on the reproductive functions of male rats

OBJECTIVE@#Bisphenol A (BPA) is a monomer primarily used in the production of polycarbonate plastic and epoxy resins. Bisphenol F (BPF) is apparently the main BPA replacement that is used increasingly. BPF has been detected in canned food, thermal paper receipts, and soft drinks. In the present experiment, we did both in vitro and in vivo studies to evaluate the effect of low and high-dose BPF exposures on testosterone concentration, oxidative stress, and antioxidants activity in reproductive tissues of male rats.@*METHODS@#Adult (80-90 days old) male Sprague Dawley rats (n = 36) obtained from the rodent colony of Animal Sciences Department of Quaid-i-Azam University. The direct effects of BPF on the antioxidant enzymes and testosterone secretion were measured in vitro and in vivo studies. In an in vivo experiment, adult male Sprague Dawley rats (n = 42) were exposed to different concentrations of bisphenol F (1, 5, 25, and 50 mg/kg/d) for 28 days. Various biochemical parameters were analyzed including the level of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), reactive oxygen species (ROS), and lipid peroxidation (LPO). Moreover, sperm motility, daily sperm production (DSP), comet assay, and histological analysis were performed.@*RESULTS@#In vitro study showed that BPF exposure significantly (p < 0.05) induced oxidative stress biomarkers, i.e., ROS and LPO, while it did not change antioxidant enzyme and testicular testosterone concentration. Whereas, an in vivo study revealed that BPF induced dose-dependent effect and high-dose (100 mg/kg) exposure of BPF significantly reduced tissue protein (p < 0.05) content, CAT (p < 0.001), SOD (p < 0.05), and POD (p < 0.05) levels while significantly (p < 0.05) augmented ROS and lipid peroxidation. Furthermore, BPF reduces testosterone, LH, and FSH secretion in a dose-dependent manner. Significant (p < 0.001) reduction in plasma and intra-testicular testosterone, LH, and FSH was noticed at 100 mg/kg BFP dose. High-dose exposure reduces spermatogenesis.@*CONCLUSION@#BPF showed an antagonistic effect on male reproductive hormones and induce alterations in testicular morphology. Increased oxidative stress and decreased testicular antioxidant status might be the underlying mechanism of BFP-induced testicular toxicity.

Di(2-ethylhexyl) phthalate-induced toxicity and peroxisome proliferator-activated receptor alpha: a review

The plasticizer di(2-ethylhexyl) phthalate (DEHP) has been widely used in the manufacture of polyvinyl chloride-containing products such as medical and consumer goods. Humans can easily be exposed to it because DEHP is ubiquitous in the environment. Recent research on the adverse effects of DEHP has focused on reproductive and developmental toxicity in rodents and/or humans. DEHP is a representative of the peroxisome proliferators. Therefore, peroxisome proliferator-activated receptor alpha (PPARα)-dependent pathways are the expected mode of action of several kinds of DEHP-induced toxicities. In this review, we summarize DEHP kinetics and its mechanisms of carcinogenicity and reproductive and developmental toxicity in relation to PPARα. Additionally, we give an overview of the impacts of science policy on exposure sources.

Ameliorative Effects of Aquilaria malaccensis Leaves Aqueous Extract on Reproductive Toxicity Induced by Cyclophosphamide in Male Rats

@#Background: Cyclophosphamide (CP) is a widely used anti-neoplastic and immunosuppressive agent that is associated with adverse side effects including reproductive toxicity. Aquilaria malaccensis (AM) is a traditional medicinal plant which was reported to exhibit high anti-oxidant and free radical scavenging properties. The present study was aimed to evaluate the protective effects of AM leaves extract on sperm quality following toxic exposure to CP. Methods: Forty-eight male Sprague Dawley rats were allocated into eight groups of six rats (n = 6): control, CP only (200 mg kg−1), AM only (100 mg kg−1, 300 mg kg−1 and 500 mg kg−1) and CP + AM (100 mg kg−1, 300 mg kg−1 and 500 mg kg−1). Animals were sacrificed after 63 days of treatment and the sperm from the caudal epididymis was taken for sperm analysis. Results: The body and the reproductive organs weight, sperm count and motility did not differ between CP and other groups (P > 0.05). A significant increase (P < 0.05) in percentage of the dead and abnormal sperm were seen in the CP alone treated group compared to the control group. Co-administration of AM to the CP exposed rats significantly reduced the (P < 0.05) percentage of abnormal sperm as compared to the CP only group. Conclusion: Overall, the present results represent the potential of AM to protect against CP induced reproductive toxicity.

Advances in reproductive toxicity of uranium and its mechanism / 局解手术学杂志

Objective Uranium, as a heavy metal material, has been used in civil and military activities in China, but it has also caused environmental pollution and human injury.In order to understand and mitigate this injury, scholars studied the damage effect of uranium through building animal models, and found that when uranium enters the animal body, it will accumulate in the body and cause damage to the body, among which the main accumulation organs are kidneys, bones, reproductive organs and so on.Sensitive organs of the role of reproductive organs is uranium, which attracted the attention of the experts, and expand the uranium exposed reproductive toxicity research.They found that the degree of toxicity of uranium is related to the time, dose and mode of uranium exposure, under certain exposure conditions, by changing the sex hormone levels in vivo, the expression of genes or proteins related to the reproductive disorders and excessive produce the mechanism, such as oxidative stress on the toxicity effect, decrease of childbirth pregnant, related to germ cell pathological histology change, and produce genetic reproductive toxicity to the offspring etc., which affect the reproductive system function, damage the health of the body.

Exposure to Atrazine Elicits Morpho-Physiological and Testicular Dysfuntions in adult male rats

@#Some of the environmental toxicants acting as endocrine disruptors have been associated with health hazards in human and wildlife by modulating hormonal actions. The widely used herbicide; atrazine (ATZ) is a potent endocrine and testicular disruptor. However, studies on it remain largely inconclusive especially whether the effects are reversible or permanent. We therefore designed this study to evaluate the histological and hormonal changes associated with differential ATZ exposure. Twenty (20) adult male Wistar rats were divided into 4 groups (5 rats per group) control and three experimental groups. Control received the vehicle; the 3 groups received ATZ, 38.5, 77.0 and 154.0 mg/kg bw/day for 30 days respectively. The effects of Atrazine were assessed through histopathological observation, spermatozoa quality examination and reproductive hormone levels. Results showed that irrespective of the ATZ dose, there was significant decrease in weight, severe pathological changes in testicular tissue, decrease in the quality of semen and altered luteinizing hormone (LH) of the rats. Taken together, our findings showed that ATZ exposure could lead to poor reproductive ability in male Wistar rats

Cyclophosphamide-induced reproductive toxicity: Beneficial effects of Helichrysum odoratissimum (Asteraceae) in male Wistar rats / 中西医结合学报

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/[kg·d], per oral administration); group 2 received CP + distilled water (10 mL/[kg·d]); group 3 received CP + 5% tween 80 (10 mL/[kg·d]); group 4 received CP + clomiphene citrate (0.25 mg/[kg·d]); groups 5 and 6 received CP + AE (50 and 100 mg/[kg·d]) and groups 7 and 8 received CP + ME (50 and 100 mg/[kg·d]). 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.

Overview of reproductive toxicity studies on Tripterygium wilfordii in recent 40 years / 中国中药杂志

This paper summarizes the research progress of reproductive toxicity of Tripterygium wilfordii from 1979,and the toxicity characterization,damage mechanism,and attenuated measures are summarized. It was found that,the reproductive toxicity caused by T. wilfordii is mainly distributed on components of Tripterygium glycosides,triptolide,tripchlorolide,and clinically preparations,such as Leigongteng Tablets and Tripterygium Glycosides Tablets. Adverse reactions to male reproductive system caused by Tripterygium preparations mainly include decreased sperm motility,oligospermia or spermatozoa,decreased fertility or infertility,etc. Long-term drug use may also lead to testicular atrophy and decreased sexual desire. Adverse reactions to women are mainly manifested as menstrual disorders,decreased menstrual volume or even amenorrhea,decreased sexual desire,infertility,etc. The reproductive toxicity of T. wilfordii is related to apoptosis of reproductive cells,disturbance of spermatogenesis or oogenesis,damage of testis and ovary in reproductive target tissues,and changes of internal environment in gonad tissues( hormones,hormone synthesis rate-limiting enzymes and energy metabolism). Drug compatibility,hormone replacement,medication duration and dosage form changes can help reduce the damage of T. wilfordii to the reproductive system. In addition,in view of the existing problems in the current study,the author proposes new directions in clinical studies,pharmacological metabolism mechanism,preparation quality standards and new therapeutic effects,etc.,to provide a basis for the safe and reasonable clinical application of T. wilfordii.

Reproductive toxicity of Triptolide on male Caenorhabditis elegans, a model organism / 中成药

AIM To study the reproductive toxicity of Triptolide,one of the main components of Tripterygium wilfordii Hook.f,on male Caenorhabditis elegans,and its potential mechanism.METHODS Expose L4 larva of him-5 nematodes to 48 h 0.02,0.2,2.0 mg/L of Triptolide.The effect of Triptolide on the fertility of male C.elegans was assessed by crossing test,and the relevant mechanism was explored through measuring spermatids morphology development,spermatids activation,sperm motility and the relative mRNA expression levels of the related spermatogenesis genes.RESULTS Compared with the solvent control group,the 48 h Triptolide treatment induced significantly decreased brood size in 2.0 mg/L Triptolide group,significant reduction in spermatid diameter,spermatid cross-sectional area,rates of spermatid activation,rates of motile sperm in 0.2 and 2.0 mg/L Triptolide groups,and decreased expression levels of spe-10 in 0.02-2.0 mg/L Triptolide groups,decreased spe-15 in 0.2-2.0 mg/LTriptolide groups,and decreased fer-1 and folt-1 in 2.0 mg/L Triptolide groups as well.CONCLUSION Triptolide decreases expression levels of the related genes in spermatogenesis,contributes to an array of indicators inhibition,the spermatids morphology development,the sperm morphology and function development,which leads to decreased fertility of male C.elegans.Therefore,spermatogenesis damage is one of the main pathway that Triptolide adversely affects the fertility.