peer reviewed | Endocrine disruption compounds (EDCs) and parasitism can both interfere with the reproduction process of organisms. The amphipod Gammarus pulex is the host of the vertically transmitted microsporidia Dictyocoela duebenum, and this work was devoted to the investigation of the effect of an exposure to the anti-androgen compound, cyproterone acetate (CPA), and/or of the presence of D. duebenum on the spermatozoa production and length. Significant reduction of the spermatozoa production was observed when G. pulex males were uninfected and exposed to CPA. There also appeared a lower number of spermatozoa when D. duebenum infects G. pulex, whatever the exposure condition. Moreover, we highlighted that CPA has no effect on spermatozoa production when males are infected by D. duebenum, and no treatment has impacted the spermatozoa length. Our results suggest CPA and D. duebenum could impact the endocrine system of G. pulex and especially processes close to the spermatozoa production (e.g., androgenic gland, androgen gland hormone released, gonad-inhibiting hormone synthesized by X-organ). However, as no mechanism of action was highlighted, further testing need to be performed to improve the understanding of their impacts. Finally, results confirm that vertically transmitted microsporidia could be a confounding factor in the endocrine disruption assessments in Gammaridae.

The antimicrobial agent triclosan (TCS) has attracted much attention worldwide because of its pervasive existence in the human body and environment. TCS exposure has been reported to be associated with decreased male reproductive function. However, few studies have investigated these associations in humans. To examine the relationship between TCS in urine and male semen quality. A total of 406 men from a reproductive clinic were enrolled in this study. Urinary TCS concentrations were determined by ultra-high performance liquid chromatography–electrospray ionization tandem mass spectrometry. Sixteen semen parameters were assessed according to the guidelines of World Health Organization (WHO), including parameters for volume, count, motility, and motion. We used multivariate linear regression models and restricted cubic splines to estimate the linear and non-linear associations between TCS exposure and semen parameters, respectively. Logistical regression models were further applied to explore the associations with abnormal semen quality. TCS was detected in 74.6% of urine specimens. The monotonous trend of TCS tertiles and continuous TCS levels with all semen quality parameters were not observed in multivariate linear regression models (p > 0.05). However, compared with those in the lowest tertile, subjects in the second tertile showed significantly higher linearity and wobble (p < 0.05), indicating potential effects on sperm motion. In the models using restricted cubic splines with 3–5 knots, there were no significant non-linear associations between TCS exposure and any semen quality parameter. In addition, TCS tertiles were not associated with the risk of abnormal semen quality (i.e., count and motility) in the logistical regression models. Our results revealed that low-level TCS exposure may have limited (none or modest) effects on male semen quality, potentially inducing some fluctuations. Further mechanistic studies on low levels of exposure are needed.

Exposure to outdoor fine particulate matter (PM₂.₅)-bound polycyclic aromatic hydrocarbons (PAHs) is linked to reproductive dysfunction. However, it is unclear which component of PAHs is responsible for the adverse outcomes. In the Male Reproductive Health in Chongqing College Students (MARHCS) cohort study, we measured the exposure levels of 16 PAHs by collecting air PM₂.₅ particles and assessed eight PAHs metabolites from four parent PAHs, including naphthalene, fluorene, phenanthrene, and pyrene in urine samples. We investigated compositional profiles and variation characteristics for 16 PAHs in PM₂.₅, and then assessed the association between PAHs exposure and semen routine parameters, sperm chromatin structure, and serum hormone levels in 1452 samples. The results showed that naphthalene (95% CI: −17.989, −8.101), chrysene (95% CI: −64.894, −47.575), benzo[a]anthracene (95% CI: −63.227, −45.936) and all the high molecular weight (HMW) PAHs in PM₂.₅ were negatively associated with sperm normal morphology. Most of the low molecular weight (LMW) PAHs, such as acenaphthylene, fluorene, phenanthrene, fluoranthene, pyrene, chrysene, benzo[a]anthracene, ∑LMW PAHs and ∑16 PAHs, were correlated with increased sperm motility (all corrected P < 0.05). On the other hand, sperm normal morphology was all negatively associated with urinary metabolites of ∑OH-Nap (95% CI: −5.611, −0.536), ∑OH-Phe (95% CI: −5.741, −0.957), and ∑OH-PAHs (95% CI: −5.274, −0.361). Urinary concentrations of ∑OH-PAHs were found to be negatively associated with sperm high DNA stainability (HDS) (P = 0.023), while ∑OH-Phe were negatively associated with serum testosterone level and sperm HDS (P = 0.004). Spearman correlation analysis showed that except for the urinary OH-Nap metabolites, the rest of the urinary OH-PAHs metabolites were negatively correlated with their parent PAHs in air. The results of this study suggest that various PAHs’ components may affect reproductive parameters differently. Inhalation of PAHs in air, especially HMW PAHs, may be a potential risk factor for male reproductive health.

Volatile Organic Compound (VOC) analysis is usually applied in pollution assessment by checking for toxic or harmful volatile compounds in air, water and soil samples. In this study, exogenous VOCs and their derivatives, metabolized by cells, were valued into specific body fluids. In particular, the VOC profiles of blood, urine and human semen samples collected from young men living in two high pollution areas in Italy, i.e. Land of Fires and Valley of Sacco River, were fingerprinted. The analysis is based on Headspace Solid Phase MicroExtraction (HS-SPME) followed by Gas Chromatography-Mass Spectrometric detection (GC-MS). The volatile composition of the three body fluids showed that some VOCs are in common between blood, urine and human semen samples, whereas others are present only in a body fluid. Some compounds, as well as also some chemical classes show a higher affinity for a specific body fluid. Statistical analysis allowed to discriminate the two contaminated areas and identify those compounds which significantly contribute to the two areas classification. Some of these compounds are toxic and found prevalently in Valley of Sacco River samples, correspondingly to sperm analysis results for young men living in this zona worse than those living in Land of Fires.

Parabens are class of preservatives used in vast majority of commercial products, and a potential Endocrine Disrupting Chemical (EDC). The present study was undertaken to delineate the effects of n-butylparaben on F1 male progeny exposed maternally through gestation and lactation via subcutaneous route. The F0 dams were given subcutaneous injections of n-butylparaben from gestation day (GD) 6 to postnatal day (PND) 21 with doses of 10, 100, 1000 mg/kg Bw/day in corn oil. The F1 male rats were monitored for pubertal development and sexual maturation; these were sacrificed on PND 30, 45 and 75. On PND 75, these F1 male rats were subjected for fertility assessment with unexposed female rats.A delayed testicular descent at 100 and 1000 mg/kg Bw dose and delayed preputial separation at 10 mg/kg Bw dose was observed in exposed F1 male rats. Decreased sperm count, motility and Daily Sperm Production was observed at 100 mg/kg Bw dose at PND 75. Interestingly, the sperm transit time in the epididymis was accelerated at this dose. Significant perturbed testicular expression of steroid receptors (ERα and β, AR), INSL3 and StAR genes with increased T and LH levels indicates direct effect on spermatogenesis and steroidogenesis. These F1 generation adult rats were sub-fertile with increased (%) pre- and post-implantation loss at 100 and 1000 mg/kg Bw/day dose. This is the first report on n-butylparaben highlighting the involvement of testicular leydig cells with accelerated sperm transit time leading to reduced fertility in the maternally exposed F1 male rats through estrogenic/anti-androgenic action.

Decabromodiphenyl ether (BDE-209) is commonly used as a flame retardant, usually in products that were utilized in electronic equipment, plastics, furniture and textiles. To identify the impacts of BDE-209 on the male reproductive system and the underlying toxicological mechanisms, 40 male ICR mice were randomly divided into four groups, which were then exposed to BDE-209 at 0, 7.5, 25 and 75 mg kg−1 d−1 for four weeks, respectively. With regard to the in vitro study, GC-2spd cells were treated with BDE-209 at 0, 2, 8 and 32 μg mL−1 for 24 h, respectively. The results from the in vivo experiments showed that BDE-209 resulted in damage to the testis structure, led to cell apoptosis in testis and decreased sperm number and motility, while sperm malformation rates were significantly increased. Moreover, BDE-209 could induce oxidative stress with decreased testosterone levels, result in DNA damage and activate DNA damage response signaling pathways (ATM/Chk2, ATR/Chk1 and DNA-PKcs/XRCC4/DNA ligase Ⅳ). The data from the in vitro experiments showed that BDE-209 led to cytotoxicity by reducing cell viability and increasing LDH release as well. BDE-209 also induced DNA strand breaks, cell cycle arrest at G1 phase and elevated reactive oxygen species (ROS) level in GC-2 cells. These results suggested that BDE-209 could lead to male reproductive toxicity by inducing DNA damage and failure of DNA damage repair which resulted in cell cycle arrest and apoptosis of spermatogenic cell. The present study provided new evidence to elucidate the potential mechanism of male reproductive toxicity induced by BDE-209.

Cadmium (Cd) is a toxic heavy metal and harmful to human health due to its ability to accumulate in organs. Previous studies have shown that Cd can induce DNA damage and autophagy. Autophagy can stabilize genetic material and DNA integrity. The aim of the present study was to determine the exact mechanism and role of autophagy induced by Cd in spermatozoa cells. Mouse spermatocyte-derived cells (GC-2) were treated with 20 μM Cd chloride for 24 h. The level of reactive oxygen species (ROS), DNA damage, autophagy and the expression of the molecular signaling pathway ATM/AMP-activated protein kinase (AMPK)/mTOR were determined. The results showed that Cd induced autophagy and DNA damage in GC-2 cells via ROS generation, and the autophagy signal pathway AMPK/mTOR was activated by ATM which is a DNA damage sensor. Melatonin, a well-known antioxidant, ameliorated DNA damage, and inhibited autophagy via the AMPK/mTOR signal pathway. Furthermore, after inhibition of autophagy by knockdown of AMPKα, increased DNA damage by Cd treatment was observed in GC-2 cells. These findings demonstrated the protective role of autophagy in DNA damage and suggested that the mechanism of autophagy induced by Cd was through the ATM/AMPK/mTOR signal pathway in spermatozoa cells.

Perfluorooctanesulphonic acid (PFOS) is a ubiquitous contaminant in the aquatic environment and our earlier studies demonstrated that chronic PFOS exposures lead to a female-biased sex ratio and decreased sperm quality in male zebrafish. The underlying mechanism for these reproductive effects is unknown. In the present study, 8 h post-fertilization (hpf) zebrafish were exposed to PFOS at 250 μg/L for 5 months, and the levels of sex hormones, expression of sex determination related genes, and histological and ultrastructural changes of gonads were fully characterized. During the sex differentiation period, we observed elevated estradiol (E2) and decreased testosterone (T) levels in whole tissue homogenates from PFOS exposed juveniles. In fully mature adult male fish, serum E2 levels were slightly increased, however, the estrogen receptor alpha (esr1) was significantly elevated in PFOS treated male gonads. Histological and electron microscopic examinations revealed structural changes in the gonads of PFOS exposed male and female adult zebrafish. In summary, chronic PFOS exposure disrupts sex hormone level and related gene expression and impairs gonadal development, which may contribute to the previously reported PFOS reproductive toxicity.

Exposure to trihalomethanes (THMs) and haloacetic acids (HAAs) has been individually associated with adverse male reproductive effects; however, their joint male reproductive toxicity is largely unknown. This study aimed to explore the joint effects of THMs and trichloroacetic acid (TCAA) on semen quality in a Chinese population. A total of 337 men presenting to the Reproductive Center of Tongjing Hospital, in Wuhan, China to seek semen analysis were included this study. Baseline blood THMs [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and urinary TCAA were analyzed and dichotomized at their median levels. The joint effects of THMs and TCAA on below-reference semen quality parameters were evaluated by calculating the relative excess risk due to interaction (RERI). After adjusting for potential confounders, we found a suggestive synergistic effect between Br-THMs (sum of BDCM, DBCM, and TBM) and TCAA for below-reference sperm count (RERI = 2.14, 95% CI: −0.37, 4.91) (P = 0.076); men with high Br-THMs and TCAA levels (above the median) had 3.31 times (95% CI: 1.21, 9.07) elevated risk of having below-reference sperm count than men with low Br-THMs and TCAA levels (below the median). No apparent joint effects were observed between THMs and TCAA for other semen quality parameters. Our results suggest that co-exposure to Br-THMs and TCAA is associated with additive effects on decreased semen quality. However, further studies in a larger sample size and mechanistic studies are needed to confirm the findings.

To investigate the association and effects of air pollution level on male semen quality in urban and rural areas, this study examines the outdoor concentrations of particulate matter (PM10), sulfur dioxide (SO2), nitrous dioxide (NO2) and semen quality outcomes for 1346 volunteers in both urban and rural areas in Chongqing, China. We found the urban area has a higher pollution level than the rural area, contrasted with better semen quality in the rural residents, especially for sperm morphology and computer assistant semen analysis (CASA) motility parameters. A multivariate linear regression analysis demonstrates that concentrations of PM10, SO2, and NO2 significantly and negatively are associated with normal sperm morphology percentage (P < 0.001) and sperm kinetic parameters. In conclusion, exposure to higher concentrations of PM10, SO2, and NO2 in urban ambient air may account for worse semen quality in urban males.