As a new type of pesticides and because of their high performance and low toxicity, pyrethroid insecticides are widely used in place of organochlorine insecticides both in agriculture and in the home. In the recent years, more and more evidence indicates that pyrethroid insecticides can reduce sperm count and motility, cause deformity of the sperm head, increase the count of abnormal sperm, damage sperm DNA and induce its aneuploidy rate, as well as affect sex hormone levels and produce reproductive toxicity. The present article reviews the advances in the studies of male reproductive toxicity of pyrethroid pesticides by experiment in animals and human population, discusses the mechanism of male reproductive toxicity of pesticides and raises some problems concerning the evaluation of human reproductive hazards.
Animals ; Genitalia, Male ; drug effects ; pathology ; physiopathology ; Humans ; Insecticides ; poisoning ; toxicity ; Male ; Mice ; Pyrethrins ; poisoning ; toxicity ; Rats ; Toxicity Tests

AIMTo assess the effect of estradiol-17beta (E(2)) and bisphenol A (BPA) administered chronically by implanting a silicone tube throughout pregnancy and lactation on male pups' reproductive system in ICR mice.

METHODSFemale mice were implanted with a tube filled with 10 ng, 500 ng, 1 microg, or 10 microg of E(2), or 100 microg or 5 mg of BPA, before mating. The tube was kept in the mice throughout pregnancy and lactation, until the pups had weaned at 4 weeks of age. During the period, E(2) was released from the tube at 120 pg or 6, 12 or 120 ng/day, and BPA at 1.2 or 60 microg/day.

RESULTSMost of the mice given 1 microg and 10 microg of E(2) did not maintain their pregnancy. However, the other groups showed high rates of birth, more than 70%. At age of 4 weeks, the male pups were killed. Body weight and reproductive organ weights (testes, epididymides and accessory reproductive glands) in the treated groups did not differ from the control values, whereas the percentage of seminiferous tubules in the testis with mature spermatids was significantly lower in the groups given 10 ng and 500 ng of E(2) and 5 mg of BPA than that in the control.

CONCLUSIONChronic exposure to E(2) and BPA might disrupt spermatogenesis in male pups.

Animals ; Benzhydryl Compounds ; Birth Rate ; Estradiol ; pharmacology ; Estrogens, Non-Steroidal ; pharmacology ; Female ; Genitalia, Male ; drug effects ; pathology ; Lactation ; Male ; Mice ; Phenols ; pharmacology ; Pregnancy ; Spermatogenesis ; drug effects

The aim of this paper was to observe the toxic effect of Tripterygium Glycosides Tablets on the reproductive system of Ⅱ type collagen induced arthritis(CIA) male rats, and to explore the toxic mechanism preliminarily. Fifty SD rats were randomly divided into normal control group(Con), model group(CIA), Tripterygium Glycosides Tablets clinical equivalent dose groups of 1, 2, 4 times(9, 18, 36 mg·kg~(-1)), 10 rats in each group, and were given by gavage once a day for 42 days after the first immunization. The organ index of testis and epididymis were calculated on days 21 and 42. Histopathological and morphological changes of testis and epididymis were observed under optical microscope. Sperm count, sperm malformation rate and sperm kinetic parameters in epididymal tissues were observed by computer assisted sperm analysis(CASA). The concentration of testosterone(T), nitric oxide synthase(NOS) and aromatase(CYP19 A1) in serum were detected by ELISA. Immunohistochemistry was used to observe the expression of Bax and Bcl-2 related proteins in the apoptosis pathway of testis and epididymis. The results showed that, compared with Con group, CIA group significantly increased the rate of testicular spermatogenic tubule lesion and sperm malformation, decreased the average path speed, and no significant changes were observed in other groups. Tripterygium Glycosides Tablets at 4 times clinical equivalent dose can significantly reduce the testis index(P<0.01), each dose group can reduce the epididymis index(P<0.05). Each dose group of Tripterygium Glycosides Tablets could cause different degrees of damage to the testis and epididymis, the proportion of testicular histopathology lesions increased, the number of spermatogenic cells in the seminiferous tubules decreased, and so on. It could reduce the number of sperm, increase the rate of sperm deformity, make the parameters of sperm dynamics abnormal, and so on. Tripterygium Glycosides Tablets at 4 times dose could significantly reduce the content of serum sex hormone T and key enzyme of androgen synthesis(P<0.05 or P<0.01), but had no effect on CYP19 A1. The expression of Bax and Bcl-2 in testis and epididymis were increased by 2 and 4 times doses of Tripterygium Glycosides Tablets(P<0.05, P<0.01 or P<0.01). The results showed that 21 d administration of Tripterygium Glycosides Tablets at equal or higher doses could induce obvious toxic effect to the reproductive organs of CIA male rats, and lower the level of serum sex hormone T and the key enzyme of androgen synthesis, NOS. The mechanism of abnormal changes of Bax and Bcl-2 in Testis and epididymis is still to be elucidated.
Animals ; Arthritis, Experimental ; Drugs, Chinese Herbal/toxicity* ; Genitalia, Male/drug effects* ; Glycosides/toxicity* ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spermatozoa/pathology* ; Tablets ; Testis/pathology* ; Tripterygium/chemistry*

OBJECTIVETo study the mechanism of male reproductive toxicity of metadoxine (MTDX) on mice and rats.

METHODSMouse multiple endpoints assay and Hershberger assay were employed to evaluate the potential estrogenic and/or antiandrogenic effects of MTDX. In mouse multiple endpoints assay, MTDX (0, 640, 1500 and 4000 mg/kg, respectively) were administered once daily p.o. for 5 days in sexually matured and ovariectomied female NIH mice. Five endpoints evaluated as markers of estrogenicity included the ratio of uterine weight to body weight, incidence and extent of uterine fluid imbibition (hydrometra), vaginal epithelial cornification during estrous cycle (estrinization) and thickness of uterine epithelial cell and stroma cell. In Hershberger assay, MTDX (0, 600 and 1500 mg/kg, respectively) was administered once daily p.o. for 10 days to castrated male SD rats with or without testosterone propionate (TP, 12.5 mg/kg, i.p. for 10 days) substitution. Relative weight of androgen dependent issues was measured.

RESULTSIn mouse multiple endpoints assay, ratio of uterine weight to body weight was 1.33, 1.38 and 1.31 x 10(-4) in MTDX 640, 1500 and 4000 mg/kg groups, respectively, without significant difference from that in control group (1.22 x 10(-4)). Thickness of uterine uterine epithelial cell (0.90 and 1.03 microm) and stroma cell (3.38 and 3.25 microm) in MTDX 1500 and 4000 mg/kg groups was not significantly different from the control group (0.85 microm and 2.77 microm, respectively). In Hershberger assay, relative weight of prostate plus seminal vesicle, levator ani muscle and bulbocavernous muscle was 1.13, 0.17 and 0.42, respectively, in the 1500 mg/kg group, significantly decreased as compared with those in the control group (1.46, 0.24 and 0.70, respectively) (P < 0.01). Relative weight of prostate plus seminal vesicle (1.29) in the MTDX 600 mg/kg group reduced slightly, with statistical significance (P < 0.05), as compared with that in the control group (1.46).

CONCLUSIONSIn the present study, MTDX did not exhibit any estrogenic effect in mice in vivo. However, it had antiandrogenic activity in castrated male SD rats, indicating that its antiandrogenic effect may be involved in it's male reproductive toxicity.

Androgen Antagonists ; toxicity ; Animals ; Drug Combinations ; Endpoint Determination ; Female ; Genitalia, Male ; drug effects ; pathology ; Male ; Mice ; Orchiectomy ; Ovariectomy ; Pyridoxine ; toxicity ; Pyrrolidonecarboxylic Acid ; toxicity ; Rats

Genistein, a soybean-originated isoflavone, is widely consumed by humans for putative beneficial health effects but its estrogenic activity may affect adversely the development of male reproductive system. Five-week-old ICR mice were purchased and fed with a soybean-based Purina Chow diet until 6 months of age. The animals were exposed by gavage to genistein (2.5 mg/kg/day) or 17beta-estradiol (7.5 microgram/kg/day) for five weeks. Corn oil was used for the negative control. The animals were fed the caseinbased AIN-76A diet throughout the experimental periods. There were no significant differences in body and organ weights of mice among experimental groups. No significant differences in sperm counts and sperm motile characteristics were found between the control and the genistein groups. Treatment of 17beta-estradiol caused a significant decrease in epididymal sperm counts compared to the control (p<0.05). The level of phospholipid hydroxide glutathione peroxidase in the epididymis of mice exposed to genistein was significantly higher than that of the control mice (p<0.05). 17beta-estradiol treatment caused a reduction of germ cells in the testis and hyperplasia of mucosal fold region in the prostate of mice. Genistein treatment did not cause any lesion in the testis, epididymis, and prostate. These results suggest that dietary uptake of genistein at adult stage of life may not affect male reproductive system and functions.
Animals ; Estradiol/metabolism ; Estrogens, Non-Steroidal/*pharmacology ; Genistein/*pharmacology ; Genitalia, Male/*drug effects/pathology ; Glutathione Peroxidase/genetics/metabolism ; Histocytochemistry/veterinary ; Male ; Mice ; Mice, Inbred ICR ; Organ Size/drug effects/physiology ; Prostate/drug effects/pathology ; RNA/chemistry/genetics ; Reverse Transcriptase Polymerase Chain Reaction/veterinary ; *Soybeans ; Sperm Count/veterinary ; Sperm Motility/drug effects/physiology

OBJECTIVETo study the mechanism of the genital system damage by nickel sulfate in male rats in order to provide the laboratory theoretical evidence for the prevention and cure of nickel genital toxicity.

METHODSThree groups of rats were injected intraperitoneally with nickel sulfate at dose of 1.25, 2.50, 5.00 mg/kg respectively for two weeks. The content of testicle nickel and blood serum testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH) were assessed with atomic absorption spectrum and radioimmuno-assay, meanwhile the activity of nitric oxide synthase (NOS) and the content of nitric oxide (NO) were measured by enzyme method.

RESULTSThe contents of testicle nickel [(0.22 +/- 0.03), (0.34 +/- 0.04), (0.41 +/- 0.02) micro g/g respectively] were increased, but the content of T, TSH, LH in blood serum were reduced; the activities of NOS in testicle tissue [(33.65 +/- 2.93), (26.53 +/- 9.52), (10.20 +/- 2.74) U/g respectively] were inhibited by nickel sulfate and the contents of NO [(0.26 +/- 0.03), (0.18 +/- 0.05), (0.15 +/- 0.02) mmol/g respectively] were decreased (P < 0.01).

CONCLUSIONNickel-induced genital system injury of male rats may be related to the decrease in the contents of T, TSH, LH, and the inhibition on NOS, as well as the fall of NO content.

Animals ; Follicle Stimulating Hormone ; blood ; Genitalia, Male ; drug effects ; metabolism ; pathology ; Luteinizing Hormone ; blood ; Male ; Nickel ; toxicity ; Nitric Oxide ; analysis ; Nitric Oxide Synthase ; analysis ; Radioimmunoassay ; Random Allocation ; Rats ; Rats, Wistar ; Testosterone ; blood

Tripterygium Glycosides Tablets has good anti-inflammatory and immunomodulatory activities,but its reproductive damage is significant. Previous studies of the research group have found that Cuscutae Semen flavonoids can improve spermatogenic cell damage caused by Tripterygium Glycosides Tablets by regulating spermatogenic cell cycle,apoptosis and related protein expression,but the mechanism of action at the gene level is still unclear. In this study,Illumina high-throughput sequencing platform was applied in transcriptional sequencing of spermatogenic cells of rats after the intervention of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets. Differentially expressed genes were screened out and the GO enrichment and KEGG pathway analysis of differentially expressed genes were conducted to explore the mechanism of Cuscutae Semen flavonoids in improving reproductive injury caused by Tripterygium Glycosides Tablets. The results showed that 794 up-regulated genes and 491 down-regulated genes were screened in Tripterygium Glycosides Tablets group compared with the blank group. Compared with Tripterygium Glycosides Tablets,440 up-regulated genes and 784 down-regulated genes were screened in the Cuscutae Semen flavonoids+Tripterygium Glycosides Tablets group. Among them,the gene closely related to reproductive function is DNMT3 L. Analysis of GO function and KEGG signaling pathway enrichment showed that the above differentially expressed genes were mainly enriched in cell,cell process,catalytic activity,binding,ovarian steroid synthesis,thyroid hormone and other functions and pathways. The thyroid hormone signaling pathway was the common enrichment pathway of the two control groups. In a word,Cuscutae Semen flavonoids has a good treatment effect on male reproductive damage caused by Tripterygium Glycosides Tablets. The mechanism may be closely related to up-regulation of DNMT3 L genes and intervention of thyroid hormone signaling pathway. At the same time,the discovery of many different genes provides valuable information for study on the mechanism of Cuscutae Semen flavonoids and Tripterygium Glycosides Tablets compatibility decreasing toxicity and increasing efficiency.
Animals ; Cuscuta ; chemistry ; DNA (Cytosine-5-)-Methyltransferases ; genetics ; Female ; Flavonoids ; pharmacology ; Genitalia ; drug effects ; pathology ; Glycosides ; toxicity ; High-Throughput Nucleotide Sequencing ; Male ; Rats ; Seeds ; chemistry ; Signal Transduction ; Tablets ; Thyroid Hormones ; genetics ; Transcriptome ; Tripterygium ; toxicity