Perfluoroalkyl substances (PFAS) are known to be endocrine-disrupting compounds, but are nevertheless widely used in consumer and industrial products and have been detected globally in human and wildlife. Data from animal and epidemiological studies suggest that PFAS may affect human fertility. This led us to consider whether maternal or paternal plasma PFAS had effects on in vitro fertilization (IVF) outcomes. The study population consisted of 96 couples who underwent IVF treatment in 2017 due to tubal factor infertility. The concentrations of 10 PFAS in blood samples from both male and female partners were measured. Poisson regression with log link was performed to evaluate the association between the tertiles of PFAS concentrations and numbers of retrieved oocytes, mature oocytes, two-pronuclei (2 PN) zygotes, and good-quality embryos, while multiple linear regression models were used to investigate the correlation between plasma PFAS and semen parameters. Multivariable logistic regression was used to evaluate the association between the tertiles of PFAS concentrations and clinical outcomes. It was found that maternal plasma concentrations of perfluorooctanoic acid (PFOA) were negatively associated with the numbers of retrieved oocytes (pₜᵣₑₙd = 0.023), mature oocytes (pₜᵣₑₙd = 0.015), 2 PN zygotes (pₜᵣₑₙd = 0.014), and good-quality embryos (pₜᵣₑₙd = 0.012). Higher paternal plasma PFOA concentrations were found to be significantly associated with reduced numbers of 2 PN zygotes (pₜᵣₑₙd = 0.047). None of the maternal or paternal PFAS were significantly associated with the probability of implantation, clinical pregnancy, or live birth. To our knowledge, the present study is the first to assess the association between parental exposure to PFAS and IVF outcomes. Our results suggest the potential reproductive effects of PFAS on both men and women, and that exposure to PFAS may negatively affect IVF outcomes. Future studies, particularly with large sample size cohorts, are needed to confirm these findings.

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.

Two areas in central-southern Italy Land of Fires in Campania and Valley of Sacco river in Lazio are known to be contaminated sites, the first due to illegal fly-tipping and toxic fires, and the second due to an intensive industrial exploitation done by no-scruple companies and crooked public administration offices with dramatic consequences for environment and resident people. The work is intended to contribute to Human BioMonitoring (HBM) studies conducted in these areas on healthy young male population by a semiconductor gas sensor array trained by SPME-GC/MS. Human semen, blood and urine were investigated. The fingerprinting of the Volatile Organic Compounds (VOCs) by a gas sensors system allowed to discriminate the different contamination of the two areas and was able to predict the chemical concentration of several VOCs identified by GC/MS.

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.

In recent years, a trend toward a declining proportion of male births has been noted in several, but not all, industrialized countries. The underlying reason for the drop in the sex ratio is unclear, but one theory states that widespread environmental endocrine disrupting chemicals affecting the male reproductive system in a negative manner could be part of the explanation. The present study was designed to investigate whether the urinary phthalate, pyrethroids and polycyclic aromatic hydrocarbons metabolites concentrations were associated with sperm Y:X ratio.The study population consisted of 194 men aged under 45 years of age who attended infertility clinic in Lodz, Poland for diagnostic purposes with normal semen concentration of 20–300 mln/ml or with slight oligozoospermia (semen concentration of 15–20 mln/ml) (WHO, 1999). The Y:X ratio was assessed by fluorescent in situ hybridization. Urinary concentrations of 1-hydroxypyrene were measured by high performance liquid chromatography, phthalate metabolites were analyzed using a procedure based on the LC-MS/MS methods and metabolites of synthetic pyrethroids were assessed by gas chromatography ion-tap mass spectrometry method.After adjustment for potential confounders (past diseases, age, abstinence, smoking, alcohol consumption, sperm concentration, motility, morphology) 5OH MEHP, CDCCA to TDCCA and 1-OHP was negatively related to Y:X sperm chromosome ratio (p = 0.033, p < 0.001, p = 0.047 respectively).As this is the first study to elucidate the association between the level of metabolites of widespread environmental endocrine disrupting chemicals (phthalates, synthetic pyrethroids, polycyclic aromatic hydrocarbons) on sex chromosome ratio in sperm therefore, these findings require further replication in other populations.

This study aimed to evaluate the adverse effects of the insecticide imidacloprid (IMI) on male spermatogenesis, steroidogenesis, and DNA damage in sexually mature and immature rats. Forty male rats (mature and immature) were equally divided into four groups: two mature and two immature groups. IMI groups of both ages were orally administered IMI in corn oil at a concentration of 1 mg/mL for kg BW/day, whereas their respective controls were orally administered corn oil only (1 mL/kg of body weight) daily for 65 days. On day 66, the rats were lightly anesthetized and then euthanized by cervical dislocation. Whole blood was collected for hemogram, serum for hormonal profile, semen for sperm profile, and testes for gene expression and histopathological, and immunohistochemical examinations. The obtained results revealed that both sexually mature and immature rats orally exposed to IMI showed serious abnormalities in sperm morphology and concentrations, with an imbalance of sexual hormones. There were increases in the level of serum 8-hydroxy-2′-deoxyguanosine and in the percentage of comet (tailed) sperm DNA in the IMI-treated groups. The results exhibited the upregulation of a DNA damage tolerance gene (8-oxoguanine glycosylase 1) and downregulation of the activity of steroidogenic genes (nuclear receptor subfamily 5, group A, member 1 and 3β-hydroxysteroid dehydrogenase). Immunohistochemical examination of the B-cell lymphoma 2-associated X apoptotic protein in testicular sections showed various degrees of apoptosis in the spermatogonial cells of the IMI-treated rats compared to the control groups. These damaging effects of IMI were more pronounced in the sexually mature rats than in the immature rats. In conclusion, despite using a low dose of IMI in the present study, there were noticeable harmful consequences on the reproductive system at different stages of sexual maturity in male rats.

Human studies indicate that phthalate exposure is associated with adverse male reproductive health, and this association may be modified by genetic polymorphisms.We investigated whether apoptosis-related gene polymorphisms modified the associations of phthalate exposure with spermatozoa apoptosis and semen quality.In this Chinese population who sought for semen examination in an infertility clinic, we measured 8 phthalate metabolites in two urine samples to assess the individual's exposure levels. Apoptosis-related gene (Fas, FasL, and caspase3) polymorphisms were performed by real-time PCR. Spermatozoa apoptosis and semen quality parameters were evaluated by Annexin V/PI assay and computer-aided semen analysis, respectively.We found that Fas rs2234767, FasL rs763110, and caspase3 rs12108497 gene polymorphisms significantly modified the associations between urinary phthalate metabolites and spermatozoa apoptosis. For example, urinary monobutyl phthalate (MBP) associated with an increased percentage of Annexin V⁺/PI⁻ spermatozoa of 25.11% (95% CI: 4.08%, 50.53%) were only observed among men with CT/TT genotype of FasL rs763110. In addition, we found that caspase3 rs12108497 gene polymorphisms significantly modified the associations of urinary mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with decreased sperm concentration and sperm count (both p-values for interactions = 0.02).Our results provided the first evidence that apoptosis-related gene polymorphisms might contribute to the effects of phthalate exposure on male reproductive health.

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.

Tobacco smoking is considered the most common reason of death and infertility around the world. This study was designed to assess the impact of tobacco heavy smoking on sperm DNA methylation patterns and to determine whether the transcription level of ALDH3B2, PTGIR, PRICKLE2, and ALS2CR12 genes is different in heavy smokers compared to non-smokers. As a screening study, the 450 K array was used to assess the alteration in DNA methylation patterns between heavy smokers (n = 15) and non-smokers (n = 15). Then, four CpGs that have the highest difference in methylation level (cg16338278, cg08408433, cg05799088, and cg07227024) were selected for validation using deep bisulfite sequencing in an independent cohort of heavy smokers (n = 200) and non-smokers (n = 100). A significant variation was found between heavy smokers and non-smokers in the methylation level at all CpGs within the PRICKLE2 and ALS2CR12 gene amplicon (P < 0.001). Similarly, a significant variation was found in the methylation level at nine out of thirteen CpGs within the ALDH3B2 gene amplicon (P < 0.01). Additionally, eighteen CpGs out of the twenty-six within the PTGIR gene amplicon have a significant difference in the methylation level between heavy smokers and non-smokers (P < 0.01). The study showed a significant difference in sperm global DNA methylation, chromatin non-condensation, and DNA fragmentation (P < 0.001) between heavy smokers and non-smokers. A significant decline was shown in the transcription level of ALDH3B2, PTGIR, PRICKLE2, and ALS2CR12 genes (P < 0.001) in heavy smokers. In conclusion, heavy smoking influences DNA methylation at several CpGs, sperm global DNA methylation, and transcription level of the PRICKLE2, ALS2CR12, ALDH3B2, and PTGIR genes, which affects negatively the semen parameters of heavy smokers.

Male infertility may be caused by genetic and/or environmental factors that impair spermatogenesis and sperm maturation. High-altitude (HA) hypoxic environments represent one of the most serious challenges faced by humans that reside in these areas. To assess the influence of the plateau environment on semen parameters, 2,798 males, including 1,111 native Tibetans and 1,687 Han Chinese individuals living in the plains (HCILP) who underwent pre-pregnancy checkups, were enrolled in this study. The semen samples of males were evaluated to determine conventional sperm parameters, sperm morphology, and sperm movement. Reproductive endocrine hormones (REHs) were detected in 474 males, including 221 Tibetans and 253 HCILP. Due to recurrent abortions in partners, the DNA fragmentation index (DFI) of 133 native Tibetans and 393 HCILP individuals was further compared. Luteinizing hormone (LH) (4.94 ± 2.12 vs. 3.29 ± 1.43 U/L), prolactin (11.34 ± 3.87 vs. 8.97 ± 3.48 nmol/L), E2/T (0.22 ± 0.11 vs 0.11 ± 0.05), median total sperm motility (61.20% vs. 51.56%), and DFI (23.11% vs. 7.22%) were higher in males from plateau areas while median progressive motility (PR) (35.60% vs. 41.12%), total number of PR sperms (51.61 vs. 59.63 mil/ejaculate), percentage of normal form sperms (3.70% vs. 6.00%), curvilinear velocity (36.10 vs. 48.97 μm/s), straight-line (rectilinear) velocity (14.70 vs. 31.52 μm/s), estradiol (103.82 ± 45.92 vs. 146.01 ± 39.73 pmol/L), progesterone (0.29 ± 0.27 vs. 2.22 ± 0.84 nmol/L), testosterone (4.90 ± 1.96 vs. 14.36 ± 5.24 nmol/L), and testosterone secretion index (ratio of testosterone to LH) (33.45 ± 22.86 vs 145.78 ± 73.41) were lower than those in males from the plains. There was no difference in median total sperm number (157.76 vs. 151.65 mil/mL), sperm concentration (52.40 vs. 51.79 mil/mL), volume (3.10 vs. 3.10 mL), total normal form sperms (5.91 vs. 6.58 mil/ejaculate, p50), and follicle-stimulating hormone (FSH) levels (4.13 ± 2.55 U/L vs 3.82 ± 2.35 U/L) between the two groups of males. The REH and sperm parameters of males from HA hypoxic environments were adaptively altered. Although the total number of PR sperm decreased and DFI increased, the Tibetan population that lives at HAs has been found to grown continuously and rapidly. These results supplement prior findings regarding the impact of HA on male reproductive function.