Declining sperm quality is a global concern, yet the roles of air pollution and greenness, and their combined effects remain insufficiently understood. We investigated the associations of indoor and ambient air pollution and residential greenness with sperm quality. A total of 2280 semen samples from two provincial-level human sperm banks were analyzed. Outdoor air pollution and greenness exposures were assessed using 15-minute walking isochrone method, and indoor exposure was quantified with a previously developed Indoor Air Pollution (IAP) index. Linear mixed models were used to evaluate associations across the spermatogenesis period. Short-term indoor or outdoor air pollution exposures were associated with lower sperm count, progressive sperm count and total motile sperm count, with the IAP index additionally related to lower sperm concentration. Residential greenness was positively associated with sperm count, progressive motility, and motile sperm count. Higher greenness levels mitigated the adverse effects of pollution on sperm count and motile sperm count. Long-term PM10 and PM2.5 exposures were related to poorer sperm quality. Mediation analysis indicated that several pollutants substantially mediated the greenness-sperm quality relationships. This study demonstrates the opposite effects of air pollution and greenspace on sperm quality, and highlights the potential reproductive benefits of improving indoor environments and expanding urban greenspace.

The decline in sperm quality has emerged as a major public health concern with significant implications for male fertility and population sustainability. However, high-accuracy biomarkers for sperm quality are lacking, and the environmental drivers remain obscure. Trihalomethanes (THMs), ubiquitous disinfection by-products in drinking water, have been linked to declining semen quality worldwide, yet the molecular mechanisms underlying THM-induced reproductive toxicity remain underexplored. In this propensity score-matched case-control study designed to maximize internal validity, we identified SP biomarkers of oligospermia and teratospermia among Chinese sperm donors and investigated their associations with THM exposure. Using deep data-independent acquisition (DIA) proteomics, we quantified 1666 SP proteins, including 73 proteins enriched in male reproductive tissues. A robust XGBoost machine learning algorithm, validated to mitigate overfitting, determined the optimal biomarker combination, achieving an AUC of 0.95. Ten oligospermia biomarkers—including five testis- or epididymis-specific proteins—were inversely associated with blood THM concentrations. These proteins regulate interconnected pathways related to oxidative stress and energy metabolism. We propose that THM—induced disruption of these fundamental metabolic machineries not only impairs sperm motility but also arrests spermatogenesis, leading to reduced sperm count. This study provides the first evidence linking SP proteomic signatures to THM exposure, offering novel insights into the mechanistic pathways of environmental reproductive toxicity.

Immune modulation is crucial for male reproduction and fertility. Metals and metalloids (metals) have been extensively studied for their immunomodulatory effects. Whether metal exposure affects semen quality through immune modulation is unclear. In the present study, we explored the associations between exogenous metals within immune cells, immune cell proportions, and semen quality among 84 healthy men who repeatedly provided 266 semen samples over 90 days. We employed mass cytometry (CyTOF) technology to identify immune cells in semen and measured exogenous metals in these cells at the single-cell resolution. After adjusting for potential confounders, most detected metals in immune cells were inversely associated with the proportion of immune cells in semen samples (all p < 0.05), indicating the adverse effects of exogenous metals on immune cells. The proportion of immune cells showed N-shaped, nonlinear associations with sperm concentration, total count, progressive motility, and total motility. Mediation analyses showed that the percentage of indirect effects of exogenous metals on sperm quality parameters via immune cells ranged from 15.11% to 54.29%. Overall, our findings unravel the indirect effects of exogenous metal exposure on male reproductive health via immune cells, contributing valuable insights into the complex interplay between environmental factors, immune cells, and human semen quality.

Toxicological studies revealed that exposure to organophosphate esters (OPEs) affects semen quality, but human evidence is controversial. Over a 3-month follow-up, 1,385 healthy young men provided 3,550 urine samples and 6,466 semen samples, which were determined for urinary OPE metabolite concentrations, sperm quality parameters, and sperm mitochondrial DNA copy number (mtDNAcn). Linear mixed models revealed inverse associations between diphenyl phosphate (DPHP) concentrations and sperm concentration [-3.81% (95% CI: -6.31, -1.24) per each 2-fold increment in exposure], total count [-4.07% (95% CI: -7.21, -0.76)], progressive motility [-0.55 (95% CI: -0.93, -0.17)], and total motility [-0.54 (95% CI: -0.91, -0.17)]; and between bis(2-butoxyethyl) phosphate (BBOEP) and diocresyl phosphate and di-p-cresyl phosphate (DoCP and DpCP) concentrations and sperm concentration [-3.61% (95% CI: -5.53, -1.58) and -3.27% (95% CI: -5.92, -0.48), respectively] and total count [-5.13% (95% CI: -7.53, -2.67) and -3.87% (95% CI: -7.21, -0.35), respectively]. These inverse associations persisted only for DPHP, DoCP and DpCP, and BBOEP measured during the epididymal storage period. Sperm mtDNAcn mediated 67.7% and 52.5%, respectively, of the associations between BBOEP and sperm concentration and total count [beta coefficient of average causal mediation effects = -0.15 (95% CI: -0.25, -0.07) and -0.18 (95% CI: -0.29, -0.08), respectively].

Toxicological studies show that disinfection byproducts (DBPs) adversely affect neurological and psychiatric symptoms, which have been linked to poor sleep quality. This cohort study explored the associations between DBP exposure, oxidative stress, and sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI) questionnaire among young healthy Chinese men who provided 710 blood and 2647 repeated urinary samples over 3 months. We measured trihalomethanes in blood and haloacetic acids and oxidative stress markers in urine samples. In adjusted models, each 2.7-fold increase in urinary trichloroacetic acid (TCAA) concentrations was associated with a greater PSQI score of 0.29 (95% confidence interval: 0.07, 0.50). A clear dose-response relationship was observed when TCAA concentrations were included as quartile variables (P for trend = 0.01). In the analyses of individual PSQI components, TCAA was associated with a greater risk of difficulty in falling asleep, short sleep duration, and daytime dysfunction (odds ratios = 1.33 (1.04, 1.70), 1.35 (1.03, 1.78), and 1.39 (1.08, 1.78), respectively, per 2.7-fold increase in TCAA concentrations). Mediation analyses showed that 4-hydroxy-2-nonenal-mercapturic acid mediated 22.24% (4.44%, 80.00%) of the association between TCAA concentrations and PSQI scores. In summary, TCAA exposure may affect sleep quality, which is partly mediated by oxidative stress.

Declining semen quality has become a global concern, with environmental exposures implicated as key contributors. In this prospective cohort study of 649 men in Wuhan, China, we investigated associations between fine particulate matter (PM2.5) components, ambient temperature, and semen quality, and explored underlying mechanisms using untargeted seminal plasma metabolomics. Bayesian Kernel Machine Regression and generalized linear models revealed that higher exposures to nitrate (NO3-), sulfate (SO42-), and temperature were independently associated with reduced sperm concentration. Specifically, a 2.72-fold increase in NO3-, SO42-, and temperature corresponded to decreases of 19.41 × 106/mL, 47.89 × 106/mL, and 36.05 × 106/mL in sperm concentration, respectively. Metabolomic profiling identified distinct metabolic signatures associated with each exposure: SO42- and temperature predominantly disrupted lipid metabolism, while NO3- exposure primarily disrupted nucleotide metabolism. Notably, three metabolites-3-hydroxybutyrylcarnitine, eicosapentaenoic acid, and uridine-were consistently linked to all exposures, indicating shared pathways involving mitochondrial dysfunction, membrane instability, and oxidative stress. These findings provide molecular evidence that co-occurring environmental stressors can impair male reproductive health via convergent metabolic mechanisms, highlighting the importance of addressing both individual and combined exposure risks.

Objective:To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. Methods:A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. Results:The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. Conclusion:Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.

Although epidemiological studies have explored the association between poly- and perfluoroalkyl substances (PFAS) concentrations and semen quality, existing findings are often inconsistent. Our work aimed to explore the association of PFAS in plasma and semen with repeated measures of semen quality parameters in healthy adults. Plasma was collected at the initial recruitment and semen was collected at least once within five predetermined intervals during an approximately 3-month period. Semen volume, concentration, motility, and total sperm count were measured in each semen specimen. PFAS was measured in individual plasma samples (n = 1252) and pooled semen samples (n = 1019) from multiple collections (or in a single semen sample if no multiple collection was available). The results reveal seminal perfluorooctanoic acid, perfluorooctanesulfonic acid, perfluorohexanesulfonic acid, and 6:2 chlorinated polyfluoroalkyl ether sulfonate were significantly associated with decreased sperm progressive motility and total motility, while multiple seminal PFAS were positively associated with sperm concentration and total sperm count. By contrast, null associations were observed between plasma PFAS and semen quality. Our study provides epidemiological evidence that PFAS exposure may affect male fertility and seminal PFAS should be measured for precise assessment of the impact of PFAS on male reproductive performances.

Background: Poor sperm quality is a major cause of male infertility. However, evidence remains scarce on how greenness affects male sperm quality. Objectives: To assess the associations of residential greenness with male sperm quality and the modification effect of air pollution exposure on the relationship. Methods: A total of 78,742 samples from 33,184 sperm donors from 6 regions across China during 2014-2020 were included and analyzed. Individual residential greenness exposures of study subjects were estimated using the Normalized Difference Vegetation Index (NDVI) during the entire (0-90 lag days) and two key stages (0-37, and 34-77 lag days) of sperm development. Contemporaneous personal exposure levels to air pollutants were estimated using a spatio-temporal deep learning method. Linear mixed models were employed to assess the impact of greenspace in relation to sperm quality. The modification effect of air pollution on the greenspacesperm quality relationship was also estimated. Results: Per IQR increment in NDVI exposure throughout spermatogenesis were statistically associated with increasing sperm count by 0.0122 (95 % CI: 0.0007, 0.0237), progressive motility by 0.0162 (95 % CI: 0.0045, modifies their relationship. These findings highlight the importance of adopting adaptable urban greenspace

There has been no comprehensive evaluation of semen characteristics in reproductive age group nationwide in China. The applicability of the current standard reference values to Chinese males is limited. This study was designed as an integrated analysis for multicentre data. We aimed to establish semen reference values for the grneral population and conduct a comprehensive evaluation of them to provide solid evidence for the current national semen status. This multicentre population-based cohort study enrolled 65,335 semen donors from 16 human sperm banks covering all 7 geographic regions, from April 20, 2013 to August 31, 2019. Healthy young men aged 20 to 45 years were included in this study. Participants were included and semen samples were analyzed according to the standard practices recommended by WHO. The study revealed significant variations in semen characteristics across different geographic regions, age groups, years, and seasons in China, but no notable declining trend was observed. A stronger decreasing trend with age was observed for the upper distributions of all semen parameters compared with the lower distribution. And age-related trends were divergent in different semen parameters. The variance-weighted estimates and 95% confidence intervals (CI) of 5th centiles were: 1.2478 ml (95% CI: 1.2477, 1.2479) for semen volume, 10.776 × 106/ml (10.749, 10.804) for sperm concentration, 16.513 × 106/ejaculate (16.304, 16.722) for total sperm count, 24.430% (24.369, 24.492) for progressive motility, 25.926% (25.861, 25.990) for total motility, and 5.829 × 106/ejaculate (5.770, 5.887) for motile sperm count. Lower reference values have been established for sperm concentration, total sperm count, progressive motility, total motility, and total motile sperm count, differing from current standard reference values. These newly developed reference values could serve as a more applicable representation of the general male population in China, benefiting from a large number of subjects that provide robust and geographically representative information.

BACKGROUND:Critical windows for exposure to chemical components of particulate matter (PM <2.5 μm in diameter [PM2.5]) associated with the human semen quality decline remain unclear. OBJECTIVES:To address this gap, we developed a new analytical framework by integrating a Linear Mixed Model (LMM) with subject- and center-specific intercepts and a Distributed Lag Model (DLM) to fully account for correlations between finely vulnerable exposure windows based on complete profile of the spermatogenesis cycle. METHODS:We constructed a multicenter cohort involving 33,234 sperm donors with 78,952 semen samples covering 6 representative regions across China from 2014 to 2020 to investigate the week-scale critical windows for the exposure. Daily exposure to PM2.5 chemical components of donors was derived from grid data based on 1-km spatial resolution surface measurements. RESULTS:Decreased sperm count was significantly associated with NO3- and SO42- at 9-10 weeks (e.g., β: -0.05 %, 95%CI: [-0.10 %, -0.00 %] at the 9th week) and 0-2 weeks (e.g., β: -0.66 %, 95%CI: [-1.24 %, -0.07 %] at the 1st week), respectively. Critical windows of progressive motility decline were 0-10 weeks for BC (e.g., β: -0.07 %, 95%CI: [-0.11 %, -0.03 %] at the 5th week), Cl- at 1-4 weeks (e.g., β: -2.21 %, 95%CI: [-3.77 %, -0.66 %] at the 2nd week), 0-6 weeks and 9-10 weeks for NO3- (e.g., β: -0.05 %, 95%CI: [-0.09 %, -0.01 %] at the 4th week), 1-3 weeks and the 8th week for NH4+ (e.g., β: -0.06 %, 95%CI: [-0.11 %, -0.01 %] at the 2nd week). Total motility is significantly negatively associated with BC at entire windows, Cl- at 0-3 weeks, the 5th week and 9-10 weeks. CONCLUSIONS:There are week-scale vulnerable windows of exposure to PM2.5 chemical components for human semen quality. This highlights the need for more targeted pollution control strategies addressing PM2.5 and its chemical components.

Background: According to the studies, more than 80% of pediatric patients with cancer can achieve a survival rate greater than 5 years; however, long-term chemotherapy and/or radiation therapy may seriously affect their reproductive ability. Fertility preservation in adolescents with cancer in China was initiated late, and related research is lacking. Analyze data to understand the current situation and implement measures to improve current practices. Methods: From 2011 to 2020, data on 275 male adolescents with cancer whose age ranged from 0 to 19 years old were collected from 16 human sperm banks for this retrospective study. Methods include comparing the basic situation of male adolescents with cancer, the distribution of cancer types, and semen quality to analyze the status of fertility preservation. Results: The mean age was 17.39 +/- 1.46 years, with 13 cases (4.7%) aged 13-14 years and 262 cases (95.3%) aged 15-19 years. Basic diagnoses included leukemia (55 patients), lymphomas (76), germ cell and gonadal tumors (65), epithelial tumors (37), soft tissue sarcomas (14), osteosarcoma (7), brain tumors (5), and other cancers (16). There are differences in tumor types in different age stages and regions. The tumor type often affects semen quality, while age affects semen volume. Significant differences were found in sperm concentration and progressive motility before and after treatment (p < 0.001). Moreover, 90.5% of patients had sperm in their semen and sperm were frozen successfully in 244 patients (88.7%). Conclusions: The aim of this study is to raise awareness of fertility preservation in male adolescents with cancer, to advocate for fertility preservation prior to gonadotoxic therapy or other procedures that may impair future fertility, and to improve the fertility status of future patients.

PurposeMale cancer survivors experience confusion about fertility following cancer treatment. The aims of this study were to evaluate survivors' semen quality in different tumor type groups in China and to analyze the current situation and challenges of male cancer patients with sperm cryopreservation.MethodsThis was a multicenter retrospective study of male patients with cancer who underwent sperm cryopreservation in 16 regions of the national sperm banks over an 11-year period from 2010 to 2020.ResultsThe number of male cancer patients with sperm cryopreservation showed an overall upward trend. The development of male cancer fertility preservation (FP) in the eastern, central, and western regions of Chinese displayed imbalance. There are seven tumor types for sperm preservation in the top incidence ten tumor types, including lymphoma, leukemia, nasopharyngeal carcinoma, sarcoma, thyroid cancer, and brain tumor. Moreover, nasopharyngeal carcinoma is a high incidence rate in China, which is related to high sperm preservation rate, different from other countries. The most percentage of males receiving sperm cryopreservation in the testicular cancers (15-39 years old) of China in 2020 was 5.55%, 1.29% in the lymphoma, and 0.39% in the leukemia. According to the type of cancer, a statistically significant lower pre-sperm density, total sperm output, and post-sperm density was observed in testicular cancers. It is worth noting that the prevalence of azoospermia 22.2% in leukemia patients attribute to urgent treatment before sperm cryopreservation. Disposition of cryopreserved sperm categories included continued storage (47.2%), discarded (9%), death (0.9%), and use (3.7%).ConclusionThis study provides the first comprehensive national statistical census and review of fertility preservation in male cancer patients with respect to trends, prevalence, and cancer types. The development of male cancer fertility preservation in China is imbalanced and percentage of males receiving sperm cryopreservation in the adolescent and young adult cancers was low. Sixteen human sperm banks from China analyze current problems and challenges, and then prioritize steps toward the achievement of the FP strategy framework for Healthy China 2030.

Although animal studies have shown the reproductive toxicity of vanadium, less is known about its effects on semen quality in humans. Among 1135 healthy men who were screened as potential semen donors, we investigated the relationships of semen quality with urinary and seminal plasma vanadium levels via inductively coupled plasma-mass spectrometry (ICP-MS). Spearman rank correlation tests and linear regression models were used to assess the correlations between average urinary and within-individual pooled seminal plasma vanadium concentrations (n = 1135). We utilized linear mixed-effects models to evaluate the associations of urinary and seminal plasma vanadium levels (n = 1135) with repeated sperm quality parameters (n = 5576). Seminal plasma vanadium concentrations were not significantly correlated with urinary vanadium concentrations (r = 0.03). After adjusting for possible confounders, we observed inverse relationships of within-individual pooled seminal plasma vanadium levels with total count, semen volume, and sperm concentration (all P values for trend < 0.05). Specifically, subjects in the highest (vs. lowest) tertile of seminal plasma vanadium concentrations had − 11.3% (−16.4%, −5.9%), − 11.1% (−19.1%, −2.4%), and − 20.9% (−29.0%, −11.8%) lower sperm volume, concentration, and total count, respectively; moreover, urinary vanadium levels appeared to be negatively associated with sperm motility. These relationships showed monotonically decreasing dose-response patterns in the restricted cubic spline analyses. Our results demonstrated a poor correlation between urinary and seminal plasma levels of vanadium, and elevated vanadium concentrations in urine and seminal plasma may be adversely related to male semen quality.

Backgrounds: Global fertility rates continue to decline and sperm quality is a prime factor affecting male fertility. Both extreme cold and heat have been demonstrated to be associated with decreased sperm quality, but no epidemiological studies have considered human adaptation to long-term temperature. Our aim was to conduct a multi-center retrospective cohort study to investigate exposure-response relationship between temperature anomaly (TA) that deviate from long-term climate patterns and sperm quality. Methods: A total of 78,952 semen samples measured in 33,234 donors from 6 provincial human sperm banks in China were collected. This study considered heat and cold acclimatization to prolonged exposure in humans and explored the exposure-response relationship between TAs and sperm quality parameters (sperm concentrations, sperm count, progressive motility, progressive sperm count, total motility and total motile sperm count) during the hot and cold seasons, respectively. Linear mixed models and generalized linear models were built separately for specific centers to pool in a meta-analysis to obtain the pooled effect of TA on sperm quality, considering repeated measurements data structure and spatial heterogeneity. Results: We identified an inverted U-shaped exposure-response relationship between TA and sperm quality during the hot season. Significant negative effect of anomalous cold on sperm quality during the hot season was found after additional adjustment for Body mass index, marital status and childbearing history. The heat-related TA in hot season was significantly negatively associated with sperm concentration, progressive sperm count and total motile sperm count (all P-values<0.05). After adjusting the relative humidity, the cold-related TA in cold season was negatively associated with the sperm total motility (P-values<0.05). Conclusions: Our results suggest both heat-related and cold-related TAs are associated with decreased sperm quality. The findings highlight the importance of reducing exposure to anomalous temperatures to protect male fertility.

While exogenous metal/metalloid (metal) exposure has been associated with reduced human semen quality, no study has assessed the associations of exogenous metals in human spermatozoa with semen quality. Here, we developed a strategy to explore the associations between exogenous metals in spermatozoa at single-cell resolution and human semen quality among 84 men screened as sperm donors, who provided 266 semen samples within 90 days. A cellular atlas of exogenous metals at the single-cell level was created with mass cytometry (CyTOF) technology, which concurrently displayed 18 metals in more than 50 000 single sperm. Exogenous metals in spermatozoa at single-cell resolution were extremely heterogeneous and diverse. Further analysis using multivariable linear regression and linear mixed-effects models revealed that the heterogeneity and prevalence of the exogenous metals at single-cell resolution were associated with semen quality. The heterogeneity of lead (Pb), tin (Sn), yttrium (Y), and zirconium (Zr) was negatively associated with sperm concentration and count, while their prevalence showed positive associations. These findings revealed that the heterogeneous properties of exogenous metals in spermatozoa were associated with human semen quality, highlighting the importance of assessing exogenous metals in spermatozoa at single-cell resolution to evaluate male reproductive health risk precisely.

Terminal N-acetylglucosamine (GlcNAc) N-linked glycosylation is a truncated N-glycosylated modification that has been reported to be involved in various diseases, such as autoimmune diseases, cancers, and neurodegenerative diseases. New and simple tools will be always valuable for further characterization of the functions of this kind of glycosylation. Our previous paper proved that an optimized lectin created from Agrocybe aegerita GlcNAc selective lectin (AANL) named AANL6, can effectively identify O-GlcNAcylation, which is terminal GlcNAc Olinked glycosylation. We speculated that AANL6 could also be used to identify terminal GlcNAc N-linked glycosylation. Using therapeutic monoclonal antibodies as a model of terminal GlcNAc N-glycosylated proteins, we proved that AANL6 could selectively identify terminal GlcNAc N-linked glycosylation. The ratio of terminal GlcNAc N-linked glycosylation was increased by enrichment with AANL6 in human serum. Using cell membrane proteins as a complex sample, we found that AANL6 bound to the sperm surface, which expresses abundant terminal GlcNAc N-glycans, but did not bind to some tumor cell surfaces such A549 and MCF-7 cells, which is rich in high mannose glycoforms. In conclusion, AANL6 was identified as a powerful tool to probe terminal GlcNAc N-linked glycosylation and would be valuable for uncovering the function of this glycosylation.

BACKGROUND:Poor sperm quality is a prevalent cause of male infertility, and the association between gaseous ambient air pollutants exposure and semen quality remains unclear.OBJECTIVES:To examine the relationship between gaseous air pollution exposure with semen quality in a large-scale and multi-center study.METHODS:We analyzed 78,952 samples corresponding to 33,234 study subjects from 2014 to 2020. The high-resolution grid pollution dataset was used to estimate personal exposures to CO, SO2, NO2 and O3 across entire stage of semen formation and three crucial stages. The linear mixed models were performed to evaluate the relationships.RESULTS:The results showed that sperm count was inversely related to SO2 exposure (-0.0070, -0.0128 to -0.0011). Decreased sperm concentration was associated with SO2 (-0.0083, -0.0142 to -0.0024), NO2 (-0.0162, -0.0320 to -0.0005) and O3 (-0.0306, -0.0480 to -0.0133) during 0-90 lag days, respectively. Additionally, we observed significant decline of PR and total motility with SO2 exposure. Similar trends were observed for SO2 and CO exposure during 3 key periods.CONCLUSIONS:Our findings suggest that exposure to gaseous air pollutants may have negative impacts on sperm quality. These findings highlight the importance that critical periods of sperm development should be considered when implementing protective measures.

Adverse male reproduction caused by phthalate ester (PAE) exposure has been well documented in vivo. However, existing evidence from population studies remains inadequate to demonstrate the impact of PAE exposure on spermatogenesis and underlying mechanisms. Our present study aimed to explore the potential link between PAE exposure and sperm quality and the possible mediation by sperm mitochondrial and telomere in healthy male adults recruited from the Hubei Province Human Sperm Bank, China. Nine PAEs were determined in one pooled urine sample prepared from multiple collections during the spermatogenesis period from the same participant. Sperm telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were determined in sperm samples. The sperm concentration and count per quartile increment in mixture concentrations were -4.10 million/mL (-7.12, -1.08) and -13.52% (-21.62%, -4.59%), respectively. We found one quartile increase in PAE mixture concentrations to be marginally associated with sperm mtDNAcn (β = 0.09, 95% CI: -0.01, 0.19). Mediation analysis showed that sperm mtDNAcn significantly explained 24.6% and 32.5% of the relationships of mono-2-ethylhexyl phthalate (MEHP) with sperm concentration and sperm count (β = -0.44 million/mL, 95% CI: -0.82, -0.08; β = -1.35, 95% CI: -2.54, -0.26, respectively). Our study provided a novel insight into the mixed effect of PAEs on adverse semen quality and the potential mediation role of sperm mtDNAcn.

Exposure to fine particulate matter (PM < 2.5 μm in diameter [PM2.5]) may accelerate human sperm quality decline, although research on this association is limited. Our objective was to investigate the relationship between exposure to the chemical constituents of PM2.5 air pollution and decreased sperm quality and to further explore the exposure-response relationship. We conducted a multicenter population-based cohort study including 78,952 semen samples from 33,234 donors at 6 provincial human sperm banks (covering central, northern, southern, eastern, and southwestern parts of China) between 2014 and 2020. Daily exposure to PM2.5 chemical composition was estimated using a deep learning model integrating a density ground-based measure network at a 1 km resolution. Linear mixed models with subject- and center-specific intercepts were used to quantify the harmful impacts of PM2.5 constituents on semen quality and explore their exposure-response relationships. Per interquartile range (IQR) increase in PM2.5 exposure levels during spermatogenesis was significantly associated with decreased sperm concentration, progressive motility, and total motility. For PM2.5 constituents, per IQR increment in Cl- (β: -0.02, 95% CI: [-0.03, -0.00]) and NO3- (β: -0.05, 95% CI: [-0.08, -0.02]) exposure was negatively associated with sperm count, while NH4+ (β: -0.03, 95% CI: [-0.06, -0.00]) was significantly linked to decreased progressive motility. These results suggest that exposure to PM2.5 chemical constituents may adversely affect human sperm quality, highlighting the urgent need to reduce PM2.5 exposure.