Cr (VI)-induced ribosomal DNA copy number variation is associated with semen quality impairment: Evidence from human to animal study.

OBJECTIVES: This study aimed to analyze the possible role of rDNA copy number variation in the association between hexavalent chromium [Cr (VI)] exposure and semen quality in semen donors and further confirm this association in mice. METHODS: In this cross-sectional study, whole blood and semen samples were collected from 155 semen donors in the Zhejiang Human Sperm Bank from January 1st to April 31st, 2021. Adult C57BL/6 J male mice were treated with different doses of Cr (VI) (0, 10, or 15 mg/kg b.w./day). Semen quality, including semen volume, total spermatozoa count, sperm concentration, progressive motility, and total motility, were analyzed according to the WHO laboratory manual. Cr concentration was detected using inductively coupled plasma mass spectrometry. The rDNA copy number was measured using qPCR. RESULTS: In semen donors, whole blood Cr concentration was negatively associated with semen concentration and total sperm counts. Semen 5 S and 45 S rDNA copy numbers were negatively associated with whole blood Cr concentration and whole blood 5.8 S rDNA copy number was negatively associated with semen Cr concentration. In mice, Cr (VI) damaged testicular tissue, decreased semen quality, and caused rDNA copy number variation. Semen quality was related to the rDNA copy number in whole blood, testicular tissue, and semen samples in mice. CONCLUSION: Cr (VI) was associated with decreased semen quality in semen donors and mice. Our findings suggest an in-depth analysis of the role of the rDNA copy number variation in the Cr (VI)-induced impairment of semen quality.

Fertility preservation in males with cancer of trends, region development, and efficacy in mainland China from 16 regions Chinese sperm banks.

PURPOSE: Male 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. METHODS: This 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. RESULTS: The 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%). CONCLUSION: This 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.

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.

[An analysis of donor semen quality in Chongqing Human Sperm Bank].

OBJECTIVE: To evaluate the quality of the donor semen in Chongqing Human Sperm Bank and the influence of age on semen parameters. METHODS: We collected semen samples from 899 donors in Chongqing Human Sperm Bank and divided them into five groups according to the age of the semen donors: 22－25, 26－30, 31－35, 36－40, and >40 years old. Using the Makler Counting Chamber, we measured the semen volume, percentage of progressively motile sperm (PMS), total motile sperm, sperm concentration, total sperm count per ejaculate, and percentage of morphologically normal sperm (MNS). Then, we compared the semen parameters obtained with the fifth percentile and median reference values published in the WHO Laboratory Manual for the Examination and Processing of Human Semen-5th Ed (WHO 5th Ed) and among different age groups using the Kruskall-Wallis H test. RESULTS: The semen volume (1.8 ml), sperm concentration (25.0 × 106/ml), total sperm count (100.7 × 106/ejaculate) and MNS (4.3%) in the semen samples of the 899 donors were obviously higher than the fifth percentile values published in the WHO 5th Ed, and so were the first three parameters (4.0 ml, 88.0 × 106/ml, and 333.7 × 106/ejaculate) than the WHO median reference values. PMS (31.0%) and total motile (38.0%) were lower than the WHO fifth percentile values and so was MNS (11.6%) than the WHO median reference value. PMS (55.0%) and total motile sperm (61.0%), however, were coincident with the median reference values of WHO 5th Ed. Statistically significant differences were observed among the 22－25, 26－30, 31－35, 36－40 and >40 years old groups in perm concentration (88.0 ï¼»1.0－270.0ï¼½ vs 96.0 ï¼»5.0－335.0ï¼½ vs 100.0 ï¼»3.0－200.0ï¼½ vs 105 ï¼»15.0－225.0ï¼½ vs 90.0 ï¼»22.0－159.0ï¼½ × 106/ml, P < 0.05), but not in the semen volume, PMS, total sperm motility, total sperm count or MNS (P > 0.05). CONCLUSIONS: The donor semen in Chongqing Human Sperm Bank is generally of high quality. Sperm concentration significantly increases with age but decreases in men aged >40 years.

[Bacterial culture of donor semen: Analysis of results].

OBJECTIVE: To investigate bacterial infection and the distribution of different bacterial species in the donor semen and the influence of different bacterial counts on semen quality. METHODS: Bacterial colonies in the semen samples from 1 126 donors were counted with the Synbiosis Protocol 3 Automatic Colony Counter and the bacterial species with a colony count ≥104 cfu/ml identified with the VITEK2 Compact Automatic Biochemical Analyzer. The Makler Sperm Counting Board was used to examine the semen quality of the semen samples with a colony count = 0 cfu/ml (n = 22, group A), those with a colony count <104 cfu/ml (n = 22, group B) and those with a colony count ≥104 cfu/ml (n = 22, group C). Univariate analysis was employed for comparison of semen quality among different groups. RESULTS: Among the 1 126 donor semen samples cultured, 5 (0.44%) showed mixed bacterial contamination and 993 (88.58%) showed none but with growth of a certain species of bacteria, 2.22% (22/993) with a colony count ≥104 cfu/ml, mainly including Streptococcus bovis, tiny bacilli, Staphylococcus epidermis, and Staphylococcus aureus, among which gram-positive and gram-negative bacteria accounted for 95.45% (21/22) and 4.54% (1/22), respectively. Compared with group A, groups B and C manifested significantly reduced total sperm count (ï¼»567.5 ± 327.6ï¼½ vs ï¼»421.9 ± 155.9ï¼½ and ï¼»389.9 ± 110.6ï¼½ × 106 per ejaculate, P <0.05) and percentage of progressively motile sperm (ï¼»65.0 ± 6.5ï¼½ vs ï¼»61.0 ± 3.5ï¼½ and ï¼»61.6 ± 4.3ï¼½ %, P <0.05). There were no statistically significant differences among the three groups in the semen liquefaction time, semen pH value, total sperm motility or percentage of morphologically normal sperm (P > 0.05). Of the 284 randomly selected semen samples, 34 (11.97%) were found positive for Ureaplasma urealyticum (UU) and no significant difference was observed in the semen quality between the UU-positive and UU-negative samples (P> 0.05). CONCLUSIONS: The bacteria-positive rate is high in the donor semen and the bacterial species are varied, mainly including gram-positive bacteria. Semen quality is reduced with the increased number of bacterial colonies.

[Analysis of the quality of cryopreserved semen from male cancer patients].

OBJECTIVE: To investigate the semen quality of cancer patients and search for a better way of sperm cryopreservation for them. METHODS: We retrospectively analyzed the quality of the semen from 43 cancer patients under cryopreservation in the Sperm Bank of Zhejiang Province, and compared the semen parameters between the cancer patients and 248 normal donors as well as between the testicular cancer cases (n=22) and non-testicular cancer cases (n=21). RESULTS: The cancer patients exhibited significantly lower semen quality than the normal donors as in sperm concentration (60.90 x 10(6)/ml vs 74.27 x 10(6)/ml), progressive motility (41.07% vs 51.79%), and recovery rate (49.98% vs 57.33%) (all P <0.05). Furthermore, the progressive sperm motility and sperm recovery rate after freezing were significantly decreased in the testicular cancer cases (15.68% and 42.81%) than in the non-testicular cancer cases (28.36% and 57.53%) (both P <0.05). CONCLUSION: Semen quality declines in cancer patients, and therefore early sperm cryopreservation is essential for them. Due to the poor sperm motility and recovery rate of testicular cancer patients after freezing, further investigation is required on the improvement of sperm cryopreservation methods.

Critical windows for exposure to chemical composition of ambient particulate matter and human semen quality decline.

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., ß: -0.05 %, 95%CI: [-0.10 %, -0.00 %] at the 9th week) and 0-2 weeks (e.g., ß: -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., ß: -0.07 %, 95%CI: [-0.11 %, -0.03 %] at the 5th week), Cl- at 1-4 weeks (e.g., ß: -2.21 %, 95%CI: [-3.77 %, -0.66 %] at the 2nd week), 0-6 weeks and 9-10 weeks for NO3- (e.g., ß: -0.05 %, 95%CI: [-0.09 %, -0.01 %] at the 4th week), 1-3 weeks and the 8th week for NH4+ (e.g., ß: -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.

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.

Beneficial effect of residential greenness on sperm quality and the role of air pollution: A multicenter population-based study.

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 greenspace-sperm 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, 0.0280), and total motility by 0.0147 (95 % CI: 0.0014, 0.0281), respectively. Similar results were observed when the model added air pollutants (PM1, PM2.5 or O3) for adjustment. Additionally, specific air pollutants, including PM1, PM2.5, and O3, were found to modify this association. Notably, the protective effects of greenness exposure were more pronounced at higher concentrations of PM1 and PM2.5 and lower concentrations of O3 (all Pinteraction < 0.05). Statistically significant positive effects of NDVI were observed on sperm motility in early spermatogenesis and sperm count in late spermatogenesis. CONCLUSIONS: Exposure to residential greenness may have beneficial effects on sperm quality and air pollution modifies their relationship. These findings highlight the importance of adopting adaptable urban greenspace planning and policies to safeguard male fertility against environmental factors.

Fertility preservation in male adolescents with cancer (2011-2020): A retrospective study in China.

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.

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.

Association of occupations with decreased semen quality in eastern China: a cross-sectional study of 12 301 semen donors.

OBJECTIVES: This study aims to examine the association between occupational factors and semen quality in semen donors in eastern China. METHODS: We recruited 12 301 semen donors from 2006 to 2020 as the studying population. A self-designed questionnaire was applied for collecting lifestyle and work style information. Semen samples were analysed according to WHO guidelines. A crude and adjusted linear regression model was used to analyse the association between occupational factors and semen quality. RESULTS: College students accounted for 36.2% of all semen donors. The majority (81.3%) of semen donors were between 18 year and 30 years. Soldiers or the police had the highest semen volume (the median value=3.8 mL), however, they had the lowest sperm concentration (53.6×106/ml) and sperm motility (45.5%). Workers in finance or insurance had an elevated risk of low semen volume, sperm concentration and total sperm count (OR=1.43, 1.57 and 1.98, respectively). Unemployed men had a high risk of low sperm concentration and low total sperm count (OR=1.84 and 1.58, respectively). Working in the information technology industry had a deleterious effect on the progressive motility of sperm (OR=1.27, 95% CI 1.03 to 1.57). CONCLUSION: Our study indicated that sedentary work style and intensive sports in certain professions might be associated with decreased semen quality. We reported evidence of becoming unemployed on the damage to semen quality. Hence, we advocate a healthy work style to improve semen quality in eastern China.

CFTR is essential for sperm fertilizing capacity and is correlated with sperm quality in humans.

BACKGROUND: Our previous studies have demonstrated the cystic fibrosis transmembrane conductance regulator (CFTR) is important for capacitation and male fertility in mouse and guinea pig spermatozoa. However, the exact function of CFTR on human sperm fertilizing capacity, and correlation with sperm quality has not been established. The present study may shed light on some unexplained male infertility, and on a possible new method for diagnosis of male infertility and strategy for male contraception. METHODS: To assess the effect of CFTR on human sperm fertilizing capacity, we examined sperm capacitation and the acrosome reaction using chlortetracycline staining, analyzed sperm hyperactivation by computer-assisted semen analysis (CASA), measured intracellular cAMP levels using ElA and evaluated sperm penetration of zona-free hamster eggs assay in fertile men. The percentage of spermatozoa expressing CFTR from fertile, healthy and infertile men (mainly teratospermic, asthenoteratospermic, asthenospermic and oligospermic) was conducted by indirect immunofluorescence staining. RESULTS: Progesterone significantly facilitated human sperm capacitation and ZP3 triggered the acrosome reaction, both were significantly inhibited by CFTR inhibitor-172 (CFTRinh-172; 10 nM-1 microM) in a dose-dependent manner. The presence of 100 nM CFTRinh-172 markedly depressed intracellular cAMP levels, sperm hyperactivation and sperm penetration of zona-free hamster eggs. In addition, the percentage of spermatozoa expressing CFTR in the fertile men was significantly higher than healthy and infertile men categories (P < 0.01). CONCLUSIONS: CFTR is essential for human sperm fertilizing capacity and the impairment of CFTR expression in spermatozoa is correlated with a reduction of sperm quality. These results suggest that defective expression of CFTR in human sperm may lead to the reduction of sperm fertilizing capacity.

Seasonal variation in semen quality in China.

In this study, we assessed the effect of seasonal variation on the semen quality in Chinese by using the average highest temperature (AHT) of the ejaculation day for partitioning season periods. A total of 13 635 semen samples were collected and analysed according to the AHT of the ejaculation day. Semen volume, sperm concentration and the percentage of spermatozoa with normal morphology in midsummer (AHT > 30 °C) were significantly lower than those in other periods of the year. Sperm motility with AHT 10-20 °C in winter and spring was significantly higher than that in other seasons. The percentage of head defects spermatozoa with AHT < 10 °C in winter was significantly lower than that in other periods. We observed that there was a significant effect of season on the semen parameters. Highest environment temperature of the day may be a determining factor for the seasonal variations in semen quality.