Effects of temperature anomaly on sperm quality: A multi-center study of 33,234 men.

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.

Adverse effects of bisphenol A and its analogues on male fertility: An epigenetic perspective.

In recent years, there has been growing concern about the adverse effects of endocrine disrupting chemicals (EDCs) on male fertility. Epigenetic modification is critical for male germline development, and has been suggested as a potential mechanism for impaired fertility induced by EDCs. Bisphenol A (BPA) has been recognized as a typical EDC. BPA and its analogues, which are still widely used in various consumer products, have garnered increasing attention due to their reproductive toxicity and the potential to induce epigenetic alteration. This literature review provides an overview of studies investigating the adverse effects of bisphenol exposures on epigenetic modifications and male fertility. Existing studies provide evidence that exposure to bisphenols can lead to adverse effects on male fertility, including declined semen quality, altered reproductive hormone levels, and adverse reproductive outcomes. Epigenetic patterns, including DNA methylation, histone modification, and non-coding RNA expression, can be altered by bisphenol exposures. Transgenerational effects, which influence the fertility and epigenetic patterns of unexposed generations, have also been identified. However, the magnitude and direction of certain outcomes varied across different studies. Investigations into the dynamics of histopathological and epigenetic alterations associated with bisphenol exposures during developmental stages can enhance the understanding of the epigenetic effects of bisphenols, the implication of epigenetic alteration on male fertility, and the health of successive generation.

Association between central obesity and semen quality: A cross-sectional study in 4513 Chinese sperm donation volunteers.

BACKGROUND: General obesity classified by body mass index has been linked to a reduction in semen quality; however, evidence on the adverse effect of central obesity on semen quality remains limited. OBJECTIVES: To investigate the association between central obesity and semen quality. MATERIALS AND METHODS: We conducted a cross-sectional study of 4513 sperm donation volunteers in Guangdong Provincial Human Sperm Bank during 2018-2021. Three central obesity indicators, including waist circumference, waist-to-hip ratio, and waist-to-height ratio, were measured using a multi-frequency bioelectrical impedance analysis for each subject. Semen analysis was conducted according to the World Health Organization laboratory manual for the examination and processing of human semen 5th edition. Linear regression models and unconditional logistic regression models were used to quantify the association between central obesity and semen parameters. RESULTS: With adjustment for age, race, education level, marital status, fertility status, occupation, year of semen collection, abstinence period, ambient temperature, and relative humidity, central obesity defined as waist circumference ≥90 cm, waist-to-hip ratio ≥0.9, or waist-to-height ratio ≥0.5 was significantly associated with a 0.27 (95% confidence interval: 0.15, 0.38) mL, 14.47 (3.60, 25.34) × 106 , 7.06 (0.46, 13.76) × 106 , and 6.80 (0.42, 13.18) × 106 reduction in semen volume, total sperm number, total motile sperm number, and total progressive motile sperm number, respectively, and a 53% (10%, 112%) increase in odds of below the World Health Organization 2010 reference value for semen volume. These associations did not significantly vary across age. Similar results were observed for central obesity defined using each of the three indicators, except that subjects with a waist circumference ≥90 cm had a slightly higher total motility (estimated change: 1.30%; 95% confidence interval: 0.27%, 2.34%) and progressive motility (estimated change: 1.27%; 95% confidence interval: 0.23%, 2.31%). DISCUSSION AND CONCLUSION: We found that central obesity was significantly associated with a reduction in semen volume, total sperm number, total motile sperm number, and total progressive motile sperm number. Future studies are warranted to confirm our results in other regions and populations.

Leydig cell metabolic disorder act as a new mechanism affecting for focal spermatogenesis in Klinefelter syndrome patients: a real world cross-sectional study base on the age.

Background: Klinefelter's syndrome (KS) was once considered infertile due to congenital chromosomal abnormalities, but the presence of focal spermatozoa changed this. The key to predict and promote spermatogenesis is to find targets that regulate focal spermatogenesis. Objective: To explore the trend of fertility changes in KS patients at different ages and identify potential therapeutic targets. Methods: Bibliometric analysis was used to collect clinical research data on KS from the Web of Science Core Collection (WoSCC) from 1992 to 2022. A cross-sectional study was conducted on 75 KS patients who underwent microscopic testicular sperm extraction (mTESE) from 2017 to 2022 in the real world. The reproductive hormones, testicular histopathology, androgen receptors, insulin-like factor 3 (INSL3) receptors and sperm recovery rate (SRR) were analyzed. Results: Male infertility, dysplasia, Sertoli cells, Leydig cells, testosterone and spermatogenesis were the research focuses related to KS. Luteinizing hormone (LH), testosterone, and INSL3 were evaluation indicators of Leydig cell function that fluctuate with age. Testosterone and LH peaked at ages 13-19 and 30-45, while INSL3 only peaked at ages 13-19. 27 patients (27/75) recovered sperm through mTESE and experienced SRR peaks at the ages of 20, 28, 34, and 37. The SRR of fibrosis patients was 46.15%, fatty degeneration was 7.14%, and melanosis was 40.00%. The INSL3 and androgen receptors were highly expressed and roughly balanced in focal spermatogenesis. Conclusion: Abnormal metabolism of Leydig cells led to imbalanced expression of INSL3 and androgen receptors, which might be a potential target for spermatogenesis in KS.

N6-methyladenosine modification of PLOD2 causes spermatocyte damage in rats with varicocele.

BACKGROUND: In recent years, N6-methyladenosine (m6A) methylation modification of mRNA has been studied extensively. It has been reported that m6A determines mRNA fate and participates in many cellular functions and reactions, including oxidative stress. The PLOD2 gene encodes a protein that plays a key role in tissue remodeling and fibrotic processes. METHODS: The m6A methylation and expression levels of PLOD2 were determined by m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) and MeRIP-quantitative polymerase chain reaction (qPCR) in the testes of varicocele rats compared with control. To determine whether IGF2BP2 had a targeted effect on the PLOD2 mRNA, RNA immunoprecipitation-qPCR (RIP-qPCR) and luciferase assays were performed. CRISPR/dCas13b-ALKBH5 could downregulate m6A methylation level of PLOD2, which plays an important role in PLOD2-mediated cell proliferation and apoptosis in GC-2 cells. RESULTS: PLOD2 was frequently exhibited with high m6A methylation and expression level in the testes of varicocele rats compared with control. In addition, we found that IGF2BP2 binds to the m6A-modified 3' untranslated region (3'-UTR) of PLOD2 mRNA, thereby positively regulating its mRNA stability. Targeted specific demethylation of PLOD2 m6A by CRISPR/dCas13b-ALKBH5 system can significantly decrease the m6A and expression level of PLOD2. Furthermore, demethylation of PLOD2 mRNA dramatically promote GC-2 cell proliferation and inhibit cell apoptosis under oxidative stress. CONCLUSION: As a result, we found that varicocele-induced oxidative stress promoted PLOD2 expression level via m6A methylation modification. In addition, targeting m6A demethylation of PLOD2 by CRISPR/dCas13b-ALKBH5 system can regulate GC-2 cell proliferation and apoptosis under oxidative stress. Taken together, our study has acquired a better understanding of the mechanisms underlying male infertility associated with oxidative stress, as well as a novel therapeutic target for male infertility.

Exposure to Fine Particulate Matter Constituents and Human Semen Quality Decline: A Multicenter Study.

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- (ß: -0.02, 95% CI: [-0.03, -0.00]) and NO3- (ß: -0.05, 95% CI: [-0.08, -0.02]) exposure was negatively associated with sperm count, while NH4+ (ß: -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.

Sperm quality decline associated with gaseous pollutant exposure: Evidence from a large cohort multicenter study.

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.

Genetic testing of sperm donors in China: a survey of current practices.

Background: The National Health and Family Planning Commission of China (NHFPCC) issued the "Measures for the Management of Human Sperm Banks," which was revised in 2003 and is still in effect today. One of the standard guidelines is that potential donors undergo laboratory testing to exclude infectious and genetic diseases and karyotype analysis. However, patient demands for donor genetic testing have also increased, and only karyotype analysis to exclude genetic diseases is not sufficient to meet these demands. Objective: To examine donor genetic screening practices at sperm banks in China and to evaluate the qualifications and skills of genetic counselors at the banks. Materials and methods: An electronic survey was distributed to twenty-seven sperm banks to examine donor genetic screening practices at sperm banks in China and to evaluate the qualifications and skills of genetic counselors at the banks. Twenty-six human sperm banks responded to a 32-question survey about their current practices related to genetic testing of sperm donors. Results: The 26 sperm banks reported that all qualified sperm donors undergo karyotype analysis; 22 banks (84.6%) collected three generations of family history from each qualified sperm donor; 10 (38.5%) reported that they attempted to accommodate special requests from donor semen recipients for particular genetic tests. Only 2 of the 26 (7.7%) sperm banks reported that they performed whole-exome sequencing. At all the sperm banks, consent for genetic testing was obtained as part of the overall contract for sperm donors. Nineteen (73.1%) sperm banks had genetic counselors on their staff, while six (23.1%) had no genetic counselors on their staff but had access to genetic counselors at the hospital. Only one (3.8%) sperm bank had no genetic counselors on their staff or at the hospital. Conclusions: The need for larger scale genetic testing of donors and recipients and an extensive panel of genetic tests specific to the Chinese population. Additionally, professionally trained geneticists must be employed as genetic counsellors so that the results of genetic tests and their implications can be explained to donors.

Heat wave exposure and semen quality in sperm donation volunteers: A retrospective longitudinal study in south China.

BACKGROUND: Previous studies have suggested an association between non-optimum ambient temperature and decreased semen quality. However, the effect of exposure to heat waves on semen quality remains unclear. METHODS: Volunteers who intended to donate sperm in Guangdong provincial human sperm bank enrolled. Heat waves were defined by temperature threshold and duration, with a total of 9 definitions were employed, specifying daily mean temperature exceeding the 85th, 90th, or 95th percentile for at least 2, 3, or 4 consecutive days. Residential exposure to heat waves during 0-90 days before ejaculation was evaluated using a validated gridded dataset on ambient temperature. Association and potential windows of susceptibility were evaluated and identified using linear mixed models and distributed lag non-linear models. RESULTS: A total of 2183 sperm donation volunteers underwent 8632 semen analyses from 2018 to 2019. Exposure to heat wave defined as daily mean temperature exceeding the 95th percentile for at least 4 consecutive days (P95-D4) was significantly associated with a 0.11 (95% confidence interval [CI]: 0.03, 0.18) ml, 3.36 (1.35, 5.38) × 106/ml, 16.93 (7.95, 25.91) × 106, and 2.11% (1.4%, 2.83%) reduction in semen volume, sperm concentration, total sperm number, and normal forms, respectively; whereas exposure to heat wave defined as P90-D4 was significantly associated with a 1.98% (1.47%, 2.48%) and 2.08% (1.57%, 2.58%) reduction in total motility and progressive motility, respectively. Sperm count and morphology were susceptible to heat wave exposure during the early stage of spermatogenesis, while sperm motility was susceptible to exposure during the late stage. CONCLUSION: Heat wave exposure was significantly associated with a reduction in semen quality. The windows of susceptibility during 0-90 days before ejaculation varied across sperm count, motility, and morphology. Our findings suggest that reducing heat wave exposure before ejaculation may benefit sperm donation volunteers and those attempting to conceive.

Association between exposure to ambient air pollution and semen quality: A systematic review and meta-analysis.

BACKGROUND: Accumulating evidence has linked exposure to ambient air pollution to a reduction in semen quality; however, the exposure-response associations are yet to be synthesized. OBJECTIVE: To summarize the exposure-response associations between air pollution and semen quality. METHODS: We systematically searched PubMed, Embase, and Web of Science for relevant studies published before April 20, 2022. Studies investigating the exposure-response association of PM2.5, PM10, SO2, NO2, CO, and O3 with semen quality written in English were included. Semen quality parameters included semen volume, sperm concentration, total sperm number, total motility, progressive motility, and normal forms. Random-effects and fixed-effects models were performed to synthesize associations in the meta-analysis. RESULTS: The search returned 850 studies, 11 of which were eligible for meta-analysis. Each 10 µg/m3 increase of exposure to PM10 and SO2 was respectively associated with a 2.18 % (95 % confidence interval [CI]: 0.10 %-4.21 %) and 8.61 % (1.00 %-15.63 %) reduction in sperm concentration, and a 2.76 % (0.10 %-5.35 %) and 9.52 % (5.82 %-13.93 %) reduction in total sperm number. Each 10 µg/m3 increase of exposure to PM2.5 and PM10 was respectively associated with a 1.06 % (95 % CI: 0.31 %-1.82 %) and 0.75 % (0.43 %-1.08 %) reduction in total motility, and a 0.55 % (0.09 %-1.01 %) and 0.31 % (0.06 %-0.56 %) reduction in progressive motility. No association was observed for PM2.5 or PM10 with semen volume; PM2.5, NO2, CO, or O3 with sperm concentration or total sperm number; and gaseous air pollutants with total or progressive motility. The association between air pollution and normal forms was not summarized due to insufficient number of studies. No significant publication bias was detected. CONCLUSIONS: Exposure to ambient PM2.5, PM10, and SO2 was inversely associated with sperm concentration, total sperm number, total motility, and/or progressive motility. Our findings add to the evidence that air pollution may lead to adverse effects on male reproductive system and suggest that reducing exposure to air pollution may help maintain better semen quality.

Association between ambient temperature and semen quality among sperm donation volunteers in South China.

BACKGROUND: Potential adverse effects of non-optimum temperatures on human semen quality have drawn much concern worldwide; however, the exposure-response relationship remains less understood. OBJECTIVES: To quantitatively assess the association between exposure to ambient temperature and semen quality in South China, and to identify potential critical exposure windows. METHODS: We conducted a longitudinal study to investigate 11,050 volunteers who lived in Guangdong province, China and intended to donate sperm in the Guangdong provincial human sperm bank during 2016-2021. Exposure to ambient temperature during 0-90 days before semen collection was assessed by extracting daily temperatures from a validated grid dataset at each subject's residential address. Linear mixed models and linear regression models were used to perform exposure-response analyses. RESULTS: During the study period, the 11,050 subjects underwent 44,564 semen analyses. Each 5 °C increase of lag 0-90 day exposure to ambient temperature was approximately linearly associated with a 3.11 (95 % confidence interval [CI]: 2.08, 4.14) × 106/ml, 9.31 (4.83, 13.80) × 106, 1.27 % (0.91 %, 1.62 %), 8.20 (5.33, 11.08) × 106, 1.37 % (1.01 %, 1.74 %), 8.29 (5.52, 11.06) × 106, 0.67 % (0.28 %, 1.05 %), and 4.50 (2.20, 6.80) × 106 reduction in sperm concentration, total sperm number, total motility, total motile sperm number, progressive motility, total progressive sperm number, normal forms, and total normal form sperm number, respectively (all p < 0.001), which was not significantly modified by age (all p for effect modification > 0.05). We identified a critical exposure period of 10-14 days before semen collection for sperm motility, and 70-90 days before semen collection for sperm count and morphology. CONCLUSIONS: Our study provides consistent evidence that higher ambient temperature was significantly associated with a reduction in semen quality in South China. The findings highlight the needs to reduce high temperature exposures during 3 months before ejaculation to maintain better semen quality.

A retrospective study on sperm cryopreservation in 1034 patients diagnosed with cancer in southern China.

Sperm cryopreservation is an effective fertility preservation method for cancer patients before anticancer treatments. However, there are little data on fertility preservation in large cohorts of patients with cancer in southern China. This retrospective cross-sectional study aimed to assess the fertility preservation status of 1034 newly diagnosed male patients with cancer in the Human Sperm Bank of Guangdong Province in southern China (Guangzhou, China). Of these, 302 patients had reproductive system tumors, mostly testicular cancers (99.0%), and 732 had other tumors, including lymphoma (33.1%), gastrointestinal cancer (16.3%), nasopharyngeal carcinoma (15.7%), leukemia (7.7%), sarcoma (3.6%), and others (23.6%). Patients with reproductive system tumors had lower sperm concentration and prefreezing and post-thawing progressive motility than those with non-reproductive system tumors (all P < 0.001). Differences in sperm concentration, progressive motility, and normal morphology rate were observed between patients with and without anticancer surgery before sperm cryopreservation (all P < 0.05). As of April 30, 2022, 63 patients used their cryopreserved sperm for assisted reproductive technology treatments and 39 pregnancies were achieved. This study provides valuable data on the fertility preservation status in newly diagnosed cancer patients in southern China, demonstrating that patients with reproductive system tumors had poor sperm quality for their pretreatment fertility preservation.

"Seminal testosterone", rising viewpoint of local spermatogenesis in nonobstructive azoospermia: One center long-term bidirectional cohort study.

Objective: Reproductive hormones are a traditional good method to evaluate spermatogenesis but might not accurately represent local spermatogenesis. To find a more accurate method, seminal reproductive hormones were studied. Methods: A bidirectional cohort study was performed. A total of 126 infertile men from 2018 to 2019 were retrospectively analyzed. They were divided into nonobstructive azoospermia (NOA), oligozoospermia (OLZ) and normal (NOR) groups. A prospective study was conducted on patients in the NOA and OLZ groups for 2 years. Microscopic testicular sperm extraction was performed for NOA patients, who were divided into a focal spermatogenesis group (FS) and an idiopathic azoospermia group (IA). Drug treatment was for OLZ patients, who were divided into a valid group (VA) and an invalid group (IN). The differences in sperm parameters and reproductive hormones were compared. ANOSIM analysis was used between and within groups. Pearson correlation analysis, CO inertia analysis and Proctor's analysis were for relationships. ROC curve for the specificity and sensitivity. Time series analysis was for the trends between hormones and time. Results: The b-FSH, b-LH, s-T and ΔT in the NOA group were significantly higher than those in the OLZ and NOR groups. However, the s-FSH, s-E2, s-P, ΔFSH, ΔLH, ΔP and ΔE2 were lower. Thirty-one NOA patients underwent MTSE, of whom 12 had sperm (FS) and 19 had no sperm (IA). The s-FSH and s-E2 of the FS group were higher than those of the IA group. Twenty-six OLZ patients completed 30 days of treatment, of which 11 had an improved sperm count (VA) and 15 had no (IN). The ΔT of the VA group was higher than that of the IN group. After follow-up for 2 years, 18 patients' results showed that b-FSH, b-LH and s-T were different over time, with delays of 19, 3 and -19 days. SC is closely related to pH, s-FSH, s-LH, s-E2, s-P, s-T, b-FSH, b-LH, ΔFSH, ΔLH, ΔP, ΔE2 and ΔT. There were complex common trends and relationships between different kinds of hormones. s-FSH, s-LH, s-E2, s-P, s-T, b-FSH and b-LH were useful to judge spermatogenesis, of which s-T, b-FSH and b-LH were more sensitive. If s-T, b-FSH and b-LH reached 64.4, 9.4 and 4.7, respectively, their prediction performance was the strongest. Conclusion: Seminal testosterone is sensitive for judging local spermatogenesis in nonobstructive azoospermia patients, which may be the direction of local spermatogenesis in nonobstructive azoospermia. Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR2200060463.

Impacts of traffic-related particulate matter pollution on semen quality: A retrospective cohort study relying on the random forest model in a megacity of South China.

BACKGROUND: Emerging evidence shows the detrimental impacts of particulate matter (PM) on poor semen quality. High-resolution estimates of PM concentrations are conducive to evaluating accurate associations between traffic-related PM exposure and semen quality. METHODS: In this study, we firstly developed a random forest model incorporating meteorological factors, land-use information, traffic-related variables, and other spatiotemporal predictors to estimate daily traffic-related PM concentrations, including PM2.5, PM10, and PM1. Then we enrolled 1310 semen donors corresponding to 4912 semen samples during the study period from January 1, 2019, and December 31, 2019 in Guangzhou city, China. Linear mixed models were employed to associate individual exposures to traffic-related PM during the entire (0-90 lag days) and key periods (0-37 and 34-77 lag days) with semen quality parameters, including sperm concentration, sperm count, progressive motility and total motility. RESULTS: The results showed that decreased sperm concentration was associated with PM10 exposures (ß: -0.21, 95 % CI: -0.35, -0.07), sperm count was inversely related to both PM2.5 (ß: -0.19, 95 % CI: -0.35, -0.02) and PM10 (ß: -0.19, 95 % CI: -0.33, -0.05) during the 0-90 days lag exposure window. Besides, PM2.5 and PM10 might diminish sperm concentration by mainly affecting the late phase of sperm development (0-37 lag days). Stratified analyses suggested that PBF and drinking seemed to modify the associations between PM exposure and sperm motility. We did not observe any significant associations of PM1 exposures with semen parameters. CONCLUSION: Our results indicate that exposure to traffic-related PM2.5 and PM10 pollution throughout spermatogenesis may adversely affect semen quality, especially sperm concentration and count. The findings provided more evidence for the negative associations between traffic-related PM exposure and semen quality, highlighting the necessity to reduce ambient air pollution through environmental policy.

Effect of ambient temperature variability on sperm quality: A retrospective population-based cohort study.

BACKGROUNDS: Abnormal sperm quality in men is one of the common causes of infertility. Both ambient temperature and extreme heat exposure have been shown to be associated with sperm quality, but there is no epidemiological evidence for the effect of ambient temperature variability. Our aim was to investigate the association between ambient temperature variability exposure and a decline in sperm quality at different stages of sperm development. METHODS: A total of 4912 semen samples collected from the Guangdong Human Sperm Bank between 1 January 2019 and 31 December 2019 were analyzed. We selected three exposure periods: the full-stage (0-90 lag days), early-stage (34-77 lag days) and late-stage (0-37 lag days) of sperm development, and then calculated the standard deviation of daily temperature (TVSD), the maximum day-to-day temperature difference (TVDmax) and the mean day-to-day temperature difference (TVDmean) for the three exposure periods. A linear mixed model was used to explore the exposure response relationship between temperature variability exposure and sperm quality indicators (including sperm concentration, sperm count and sperm motility). RESULTS: There was a significant negative association of decreased sperm count with the exposure to temperature variability during 0-90 days prior to sperm collection. (TVDmax: -0.041; -0.063, -0.019; TVDmean: -0.237; -0.386, -0.088; TVSD: -0.103; -0.196, -0.011). We observed a significant association between the decline in sperm concentration, sperm count and per 1 °C increase in TVDmean during early spermatogenesis. No significant association of temperature variability with sperm motility was found. CONCLUSIONS: The results indicate that exposure to temperature variability during the entire period of sperm development is significantly associated with a decline in sperm counts. We found that mean day-to-day temperature differences had a detrimental effect on sperm counts in the early-stage. Our findings provide a scientific basis for public health policy and further mechanistic studies.

Risk Prediction of Ureaplasma urealyticum Affecting Sperm Quality Based on Mathematical Model and Cross-Sectional Study.

Objective: To explore the risk of Ureaplasma urealyticum (UU) affecting sperm quality. Methods: Prospective cross-sectional study was conducted. In total, 340 semen samples were collected. According to whether they were infected with UU, the samples were divided into the UU-positive group (observation group) and UU-negative group (control group). The patients with UU-positive were followed up to obtain treatment and collected the semen again after treatment. The semen characteristics and sperm parameters were detected and compared, and the relationship of UU and the sperm quality was analyzed by mathematical models. Results: There were 104 UU-positive semen samples in all, with an overall infection rate of 30.6%, which was highest in 31 to 40-year-old men, and over 40-year-old men were the lowest. The pH, PR, VCL, VSL, and STR in the observation group were significantly lower than those in the control group (allP < 0.001), while SV, NP, and WOB were significantly higher (allP < 0.001). After treatment, the pH, VSL, LIN, WOB, and STR in the observation group were significantly higher than before (allP < 0.001), while SV and VCL were significantly lower (allP < 0.001). UU infection was closely correlated with pH, PR, NP, VCL, VSL, WOB, and STR. During the treatment, pH, PR, VSL, WOB, and STR increased, but NP and VCL decreased. 7 major factors that would affect SQ were extracted, of which VAP, LIN, and UU were the first three main factors. The risk of SQ declining after UU infection increased nearly twice with the change of PR and VCL and increased 0.08 times with STR. Conclusion: UU may approximately double the risk of altering the sperm's curvilinear movement rate and straightness to affect the sperm quality.

H3K36me2 methyltransferase NSD2 orchestrates epigenetic reprogramming during spermatogenesis.

Spermatogenesis is precisely controlled by sophisticated gene expression programs and is driven by epigenetic reprogramming, including histone modification alterations and histone-to-protamine transition. Nuclear receptor binding SET domain protein 2 (Nsd2) is the predominant histone methyltransferase catalyzing H3K36me2 and its role in male germ cell development remains elusive. Here, we report that NSD2 protein is abundant in spermatogenic cells. Conditional loss of Nsd2 in postnatal germ cells impaired fertility owing to apoptosis of spermatocytes and aberrant spermiogenesis. Nsd2 deficiency results in dysregulation of thousands of genes and remarkable reduction of both H3K36me2 and H3K36me3 in spermatogenic cells, with H3K36me2 occupancy correlating positively with expression of germline genes. Nsd2 deficiency leads to H4K16ac elevation in spermatogenic cells, probably through interaction between NSD2 and PSMA8, which regulates acetylated histone degradation. We further reveal that Nsd2 deficiency impairs EP300-induced H4K5/8ac, recognized by BRDT to mediate the eviction of histones. Accordingly, histones are largely retained in Nsd2-deficient spermatozoa. In addition, Nsd2 deficiency enhances expression of protamine genes, leading to increased protamine proteins in Nsd2-deficient spermatozoa. Our findings thus reveal a previously unappreciated role of the Nsd2-dependent chromatin remodeling during spermatogenesis and provide clues to the molecular mechanisms in epigenetic abnormalities impacting male reproductive health.

Evaluating an external quality assurance program for semen analysis in China during 2009-2020.

INTRODUCTION: Semen analysis (SA) plays a key role in guiding treatments of male reproductive diseases and infertility due to male factors; however, it remains challenging to conduct an accurate SA due to lack of standardization, highly subjective assessments, and problems with automated procedures. Therefore, quality assurance (QA) and teaching courses are essential for making the laboratory results more consistent. MATERIALS AND METHODS: The external quality assurance (EQA) scheme was organized by national human sperm bank technology training bases in Guangdong province in China between 2009 and 2020. Until 2020, 124 laboratories from China participated in the EQA program. The EQA scheme per year has been organized involving two semen aliquots for sperm concentration, two video recordings for motility, and two smears for sperm morphology. All samples used in the EQA scheme were obtained from different healthy donors or patients. RESULTS: We estimated that the median coefficient of variation (CV) of sperm concentration, ignoring the method used, was 26.6%. Using a 100 µm deep counting chamber led to a decreasing CV of 13.6%. For sperm motility, the median CV of nonprogressive motility was high (50.8%), but the CV of progressive motility (13.2%), immotile sperm (14.3%), and total motility (11.8%) were acceptable. The morphology assessment revealed large variability (44.4%) irrespective of the classification criteria. DISCUSSION: The reduction of interlaboratory variability is still a challenge during SA in China. Therefore, it is critical to increase awareness of joining EQA schemes and establish standardized training centers to follow WHO-recommended procedures toward Chinese standards.

Ureaplasma urealyticum induces polymorphonuclear elastase to change semen properties and reduce sperm motility: a prospective observational study.

OBJECTIVE: To elucidate the mechanism underlying how Ureaplasma urealyticum (UU) affects sperm quality and identify a therapeutic target. METHODS: In this prospective observational study, the differences in and relationships among semen volume, pH, viscosity, liquefaction time, sperm concentration, sperm motility [progressive motility (PR)], and seminal polymorphonuclear (PMN) elastase were analyzed in 198 normal semen samples (control group) and 198 UU-infected semen samples (observation group). The UU-infected samples were treated and the above parameters were compared between the two groups. RESULTS: The semen volume, viscosity, liquefaction time, and seminal PMN elastase were significantly higher in the observation than control group, but the pH and PR were significantly lower. In the observation group, the pH and PR were significantly higher after than before treatment, whereas the semen volume, PMN elastase, viscosity, and liquefaction time were lower. UU was closely related to semen volume, pH, viscosity, liquefaction time, sperm motility (PR), and PMN elastase. PMN elastase had significant negative effects on semen pH and sperm motility (PR) but positive effects on viscosity and liquefaction time. CONCLUSION: UU might induce PMN elastase to increase the liquefaction time and viscosity of semen, eventually decreasing PR. PMN elastase might be a therapeutic target of UU.