Environmental factors may negatively contribute to a progressive worsening of semen quality, and differences in semen quality may result from different environmental exposures (regional differences) or lifestyle differences. Heavy metals are factors with a confirmed negative influence on male fertility. Among them, lead and cadmium are commonly found in human surroundings. Thus, we analyzed semen parameters (according to the World Health Organization 2010 recommendations) and semen lead and cadmium concentrations in 188 men from two different regions in Poland, a typical agricultural area and an industrial area, in couples that had been diagnosed with infertility. The assays were performed using flameless electrothermal atomic absorption spectrometry. In the statistical analysis, regional comparisons and then taxonomic comparisons based on three parameters (age, semen concentration, and sperm morphology) were applied. We showed that more cadmium than lead accumulated in semen, a higher cadmium concentration was observed in semen obtained from men from the agricultural region, and better semen quality and lower cadmium concentrations were found in the semen of men from the industrial, more polluted region. We thus showed an existing regionalism in the sperm quality properties. However, semen parameters such as morphology and progressive and nonprogressive motility followed the same trends, regardless of the patient's age, region, or class. We could conclude that the environment has a minor impact on sperm morphology and progressive and nonprogressive motility and that other existing factors could have an indirect influence on semen quality.
Cadmium ; Environmental Exposure/analysis* ; Humans ; Infertility, Male/chemically induced* ; Male ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa

An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%-87% of mice die when administered an intraperitoneal injection of 40 mg kg^-1. In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg^-1) on day 36 or a dose of 40 mg kg^-1 at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg^-1 busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg^-1 in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity.
Adult Germline Stem Cells/transplantation* ; Animals ; Azoospermia/chemically induced* ; Busulfan/toxicity* ; Disease Models, Animal ; Infertility, Male/chemically induced* ; Injections, Intraperitoneal ; Male ; Mice ; Spermatogenesis/drug effects* ; Spermatogonia/drug effects* ; Stem Cell Transplantation/methods*

ObjectiveTo screen out an effective substitute in the prescription of Shengjing Capsules (SJC), observe the effects of the redeveloped New SJC (NSJC) with cordyceps cephalosporium mycelia (CCM) substituted for the ingredient cordyceps sinensis in the treatment of spermatogenesis impairment (SI), and provide some experimental evidence for its application in the treatment of male infertility and sexual dysfunction.

METHODSWe equally randomized 192 male mice into 16 groups: normal saline control, SI model, high-, medium- and low-dose fermented cordycepin powder (FCP, 1.60, 0.80 and 0.40 g/kg), high-, medium- and low-dose CCM (1.60, 0.80 and 0.40 g/kg), high-, medium- and low-dose cordyceps mortierella mycelia (CMM, 1.60, 0.80 and 0.40 g/kg), high-, medium- and low-dose fermented cordyceps sinensis (FCS, 1.60, 0.80 and 0.40 g/kg), SJC (0.80 g/kg), and vitamin E (VE, 0.25 g/kg), with the SI model established in all the mice and the normal controls injected intraperitoneally with cyclophosphamide at 60 mg/kg qd for 5 consecutive days. After intragastrical medication with respective drugs, we obtained the body mass index (BMI), sexual organ coefficient, sperm count, sperm motility, and percentage of morphologically abnormal sperm (MAS) of the mice. We also randomly divided 70 male rats into 7 groups of equal number: normal control, SI model, high-, medium- and low-dose NSJC (1.12, 0.56 and 0.28 g/kg), SJC (0.56 g/kg), and VE (0.18 g/kg), the SI model constructed in the latter 6 groups of rats by gavage of adenine at 200 mg/kg qd for 5 consecutive days. After intragastrical medication with respective drugs, we examined the BMI, coefficients of sexual and renal organs, levels of reproductive hormones, testicular morphology, and fertility of the animals.

RESULTSAfter medication, the mice in different groups showed different degrees of improvement in the cyclophosphamide-induced slow growth, significant increases in the testicular and epididymal coefficients, sperm count, motility and viability (P < 0.05 or P < 0.01), and a remarkable reduction in the percentage of MAS (P < 0.05 or P < 0.01). The effect was particularly significant in the CCM group and therefore CCM was chosen as the best substitute ingredient in the redeveloped NSJC. Compared with the rats in other groups, those treated with NSJC exhibited significant increases in the BMI, coefficients of sexual and renal organs and levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and estradiol (E2) (P < 0.05 or P < 0.01), improvement of the pathologically damaged testicular morphology, elevation of the pregnancy rate and litter size, and recovery from adenine-induced SI.

CONCLUSIONSThe redeveloped New Shengjing Capsules with cordyceps cephalosporium mycelia substituted for the ingredient cordyceps sinensis can improve fertility and reverse spermatogenesis impairment in male rats. The new prescription may also be applied to the clinical treatment of male infertility and sexual dysfunction.

Acremonium ; Animals ; Capsules ; Cordyceps ; Cyclophosphamide ; Drugs, Chinese Herbal ; Epididymis ; Estradiol ; blood ; Fertility ; Follicle Stimulating Hormone ; blood ; Infertility, Male ; chemically induced ; therapy ; Luteinizing Hormone ; blood ; Male ; Mycelium ; Random Allocation ; Rats ; Species Specificity ; Sperm Count ; Sperm Motility ; Spermatogenesis ; Spermatozoa ; Testis ; anatomy & histology ; Testosterone ; blood

In recent years, the incidences of male infertility and recurrent abortion are increasing. The causes of the conditions are varied and complex, but the affected stability of the genetic material in the sperm is an important etiological factor. Environmental pollutants may invade the body through respiration, diet and other channels, resulting in infertility and abortion or even affecting the reproductive system development of the offspring by changing the epigenetics of sperm DNA. In this paper, we propose the idea of using traditional Chinese medicine to prevent environmental pollutant-induced epigenetic changes of sperm DNA, hoping to provide a new insight into the protection against genetic material damage, male infertility, and recurrent abortion caused by environmental pollutants.
DNA Damage ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Environmental Pollutants ; toxicity ; Epigenesis, Genetic ; Humans ; Infertility, Male ; chemically induced ; prevention & control ; Male ; Medicine, Chinese Traditional ; Spermatozoa ; drug effects

OBJECTIVETo observe the effects of Qiangjing Tablets (QJT) on the semen quality and Fas/FasL signaling pathway in male SD rats with infertility.

METHODSModels of infertility were made in 50 male SD rats by intragastric administration of Tripterygium (GTW) for 3 weeks, and another 20 rats were taken as blank controls. Then 40 successfully established rat models were randomly divided into four groups, model control, low-dose QJT, medium-dose QJT, and high-dose QJT, the latter three groups treated intragastrically with QJT at 58 mg, 105 mg, and 233 mg per kg of the body weight per day, respectively. After 4 weeks of medication, the rats were killed for examination of semen quality and determination of the expression of the apoptosis factor FasL in the testis tissue.

RESULTSCompared with the blank controls, the model rats showed significant decreases in sperm concentration ([71.99 ± 9.72] vs [10.94 ± 3.58] x 10⁶/ml, P < 0.01), motility ([48.95 ± 4.10] vs [9.31 ± 5.79]%, P < 0.01), and viability ( [82.06 ± 6.16] vs [24.03 ± 6.93]%, P < 0.01). In comparison with the model controls, the rats in the QJT groups exhibited remarkably increased sperm concentration, motility, and viability, more significantly in the high-dose group ([59.66 ± 4.53] x 10⁶/ml, [35.45 ± 5.21] %, and [61.97 ± 9.75]%) and medium-dose group ([40.89 ± 4.90] x 10⁶/ml, [24.41 ± 4.79]%, and [60.06 ± 10.62]%) (P < 0.05 or P < 0.01). The expression of FasL was markedly reduced in the low-, medium-, and high-dose QJT groups (0.5215 ± 0.0189, 0.5371 ± 0.0364, and 0.4556 ± 0.0215) as compared with that of the model controls (0.5989 ± 0.0448 ) (P < 0.05 or P < 0.01).

CONCLUSIONBy upregulating the Fas/FasL signaling pathway, Tripterygium glycosides may induce the apoptosis of spermatogenic cells and reduce sperm concentration, motility and viability, resulting in infertility. The Chinese medicine Qiangjing Tablets can improve the reproductive function of male rats by decreasing the expression of the apoptosis factor FasL in the testis.

Animals ; Apoptosis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Fas Ligand Protein ; drug effects ; metabolism ; Germ Cells ; Glycosides ; Infertility, Male ; chemically induced ; drug therapy ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Semen ; drug effects ; Semen Analysis ; Signal Transduction ; Sperm Count ; Sperm Motility ; drug effects ; Tablets ; Testis ; drug effects ; metabolism ; Tripterygium

The reproductive toxicity of environmental endocrine disruptors has attracted substantial attention from researchers in recent years. Bisphenol A (BPA) is among the most prominent environmental estrogens worldwide, demonstrated to be related with the impairment of male reproductive function as well as other health problems, such as diabetes, obesity, cardiovascular diseases, and cancer. BPA acts primarily by mimicking antiandrogenic and estrogenic effects, disturbing the hypothalamic-pituitary-testicular axis and modulating gene expressions and enzyme activities in the hormone biosynthesis affecting steroids or its receptors. BPA is also involved in DNA methylation and the effects of epigenetics, resulting in dyszoospermia, oligoasthenoteratospermia/azoospermia and/or infertility in males. This review addresses the effects of BPA on male reproductive function, focusing on the mechanisms of its toxicity on spermatogenesis, semen quality, and the reproductive system.
Benzhydryl Compounds ; toxicity ; Endocrine Disruptors ; toxicity ; Endocrine System ; drug effects ; Environmental Pollutants ; toxicity ; Estrogens ; toxicity ; Humans ; Infertility, Male ; chemically induced ; Male ; Phenols ; toxicity ; Semen Analysis ; Spermatogenesis ; drug effects

OBJECTIVETo observe the influence of different concentrations of bisphenol A (BPA) on glucose metabolism and lactate dehydrogenase (LDH) expression in rat Sertoli cells in vitro and investigate the mechanisms of BPA inducing male infertility.

METHODSUsing two-step enzyme digestion, we isolated Sertoli cells from male Wistar rats and constructed a primary Sertoli cell system, followed by immunohistochemical FasL staining. We randomly divided the Sertoli cells into a control group to be cultured in the serum-free minimal essential medium (MEM) plus dimethyl sulfoxide (DMSO) and three experimental groups to be treated with 100 nmol/L, 10 μmol/L, and 1 mmol/L BPA, respectively, in the MEM plus DMSO. After 48 hours of treatment, we measured the proliferation of the cells by CCK-8 assay, determined the concentrations of metabolites by NMR spectroscopy, and detected the expression of LDH in the Sertoli cells by RT-PCR and Western blot.

RESULTSThe purity of the isolated Sertoli cells was (96.05 ± 1.28)% (n = 10). Compared with the control group, the 100 nmol/L, 10 μmol/L, and 1 mmol/L BPA groups showed no remarkable changes in the proliferation of Sertoli cells ([98 ± 8]%, [96 ± 3]%, and [95 ± 3]%, P >0.05), but the 10 μmol/L and 1 mmol/L of BPA groups exhibited significantly decreased concentrations of intracellular glucose ([3.89 ± 0.07] vs [3.36 ± 0.24] and [3.04 ± 0.21] pmol/cell, P <0.05) and lactate ([0.43 ± 0.06] vs [0.29 ± 0.05] and [0.20 ± 0.03] pmol/cell, P <0.05). The expression of LDH mRNA was decreased with the increased concentration of BPA, while that of LDH protein reduced only in the 1 mmol/L BPA group (P <0.05).

CONCLUSIONHigh-concentration BPA decreases the expression of LDH and alters glucose metabolism in Sertoli cells, and therefore may reduce the provision of lactate for germ cells and impair spermatogenesis.

Animals ; Benzhydryl Compounds ; administration & dosage ; pharmacology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Culture Media, Serum-Free ; Dimethyl Sulfoxide ; pharmacology ; Glucose ; metabolism ; In Vitro Techniques ; Infertility, Male ; chemically induced ; L-Lactate Dehydrogenase ; metabolism ; Male ; Phenols ; administration & dosage ; pharmacology ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Sertoli Cells ; drug effects ; metabolism ; Spermatogenesis ; drug effects

Fluorosis of coal burning is a new type of endemic fluorosis in China, which affects the male reproductive system. Furthermore, the content of fluoride in the semen, sperm mortality, sperm concentration and the incidence of infertility are higher in severe fluorosis areas than in mild- and non-fluorosis areas, so are the levels of serum follicle-stimulating hormone and luteinizing hormone. However, the levels of inhibin B, serum testosterone and estradiol show different degrees of reduction in severe fluorosis areas. Accordingly, fluorosis of coal burning, just like other endemic fluorosis, may affect the structure of male reproductive organs, the generation of sperm and reproductive endocrinology, resulting in the decline of men's reproductive ability.
Coal ; Fluorosis, Dental ; blood ; etiology ; Follicle Stimulating Hormone ; blood ; Humans ; Infertility, Male ; chemically induced ; Male ; Semen ; chemistry ; Smoke ; adverse effects ; Spermatozoa ; drug effects

OBJECTIVETo investigate the incidence and spermatogenesis of cryptorchid testes induced by postnatal injection of estradiol.

METHODSNinety male newborn Balb/C mice were randomly divided into an experimental (n = 60), a solvent control (n = 20) and a normal control group (n = 10). The experimental mice were again assigned to a 4-week, a 6-week, an 8-week, and a 10-week subgroup, and injected subcutaneously with 17-beta estradiol (5 microg/d) from 3 to 28, 3 to 42, 3 to 56 and 3 to 70 days after birth, respectively. The incidence of cryptorchidism and morphological changes of the testes were observed at 2 weeks after drug withdrawal.

RESULTSThe incidence rates of cryptorchidism in the 4-, 6-, 8- and 10-week groups were 0%, 26.7%, 60% and 60%, respectively, but no cryptorchidism occurred in the solvent and normal control groups. The 4- and 6-week groups showed autonomous descent of the cryptorchid testes and recovery of spermatogenesis after drug withdrawal. The models became stable and no spermatogenesis recovery was observed after 8 weeks of continuous medication.

CONCLUSIONStable cryptorchid infertile models can be established in mice by postnatally continuous injection of estradiol for over 8 weeks.

Animals ; Animals, Newborn ; Cryptorchidism ; chemically induced ; Disease Models, Animal ; Estradiol ; adverse effects ; Infertility, Male ; chemically induced ; Male ; Mice ; Mice, Inbred BALB C

OBJECTIVETo investigate the regulatory effect of Yijing Fang (YJF) on adenine-induced infertility in rats with kidney deficiency.

METHODSSixty healthy Wistar male rats, aged 1.5 mo and weighing (180 +/- 10) g, were normally fed for a week, and then divided into five groups of equal number (blank control, infertile model, high-dose YJF, mid-dose YJF, and low-dose YJF) according to the body weight of the rats. The models were made by intragastric administration of 500 mg/ml adenine in gum arabic solution in the ratio of 1:10 at the dose of 1 ml per 100 g body weight per day for 10 days. YJF was given at 3.38 g, 1.69 g and 0.85 g per 100 g body weight per day to the rats in the high-, mid- and low-dose groups, respectively. After 48 days of treatment, we observed kidney deficiency-related changes in sperm concentration and motility, the levels of testosterone (T) and other hormones and the volumes of the testis, epididymis, seminal vesicle and prostate, and compared the indexes among different groups.

RESULTSYJF exhibited a significant regulatory effect on sperm concentration and motility, the T level and the indexes of the gonad and other accessory glands in the model rats (P < 0.05). After 48 days of treatment, sperm concentrations were (87.85 +/- 28.44), (7.11 +/- 2.15), (35.98 +/- 14.04), (32.65 +/- 11.80) and (33.51 +/- 13.26) x 10(6)/ml in the blank control, infertile model, high-dose YJF, mid-dose YJF, and low-dose YJF groups, respectively; sperm motilities were (52.79 +/- 16.43), (31.14 +/- 3.07), (45.88 +/- 16.97), (51.56 +/- 13.35) and (49.53 +/- 10.16)%; the T levels were (194.07 +/- 40.29), (61.27 +/- 13.70), (121.87 +/- 24.35), (127.44 +/- 19.38) and (127.81 +/- 20.28) nmol/L; the luteinizing hormone (LH) levels were (7.017 +/- 0.269), (6.117 +/- 0.894), (7.060 +/- 0.871), (7.156 +/- 0.937) and (6.967 +/- 0.778) IU/L; the testis volumes were (3.775 +/- 0.183), (2.865 +/- 0.258), (3.236 +/- 0.058), (3.457 +/- 0.066) and (3.398 +/- 0.091) g; the epididymis volumes were (1.119 +/- 0.116), (0.833 +/- 0.226), (1.124 +/- 0.104), (1.132 +/- 0.107) and (1.114 +/- 0.106) g; the prostate volumes were (176.75 +/- 427.09), (131.67 +/- 39.45), (178.70 +/- 37.97), (180.11 +/- 37.39) and (179.00 +/- 35.42) mg; and the body weights were (188.50 +/- 7.12), (189.92 +/- 6.67), (187.42 +/- 5.47), (189.17 +/- 6.19) and (188.75 +/- 6.12) g. Testis histopathology showed obvious injuries in the infertile models and different degrees of improvement in the three YJF groups, most evidently in the mid-dose group.

CONCLUSIONYifing Fang had an evident therapeutic effect on kidney deficiency-related infertility in adenine-induced rat models.

Adenine ; adverse effects ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Infertility, Male ; chemically induced ; drug therapy ; Male ; Phytotherapy ; Rats ; Rats, Wistar