Exposure to PM2.5 is associated with an increased risk of preterm birth (PTB), yet the key constituents and underlying pathways remain unclear. Gestational diabetes mellitus (GDM), which is also linked to PM2.5, may mediate this association. This study aims to investigate the associations between PM2.5, GDM, and PTB using the Mendelian randomization (MR) as an initial exploratory tool to assess potential causal associations, and subsequently using a large-scale cohort study to provide pregnancy-specific estimates and conduct mediation analyses, with a particular attention on PM2.5 pollution events (> World Health Organization's interim target III for daily PM2.5) and constituents. In the European MR analysis, univariable models suggested causal associations between GDM and PTB, as well as between PM2.5 and GDM; however, multivariable models indicated that PM2.5 absorbance, rather than PM2.5 itself, was positively associated with PTB. In the East Asian MR analysis, no significant association was observed between PM2.5 and GDM, but PM2.5 absorbance exhibited a strong positive association with GDM. In cohort study, PM2.5 events were associated with both GDM and PTB when combined with high-BC concentrations, with BC showing the strongest independent effect on both outcomes among the major PM2.5 constituents. Notably, there was no significant association between low-BC PM2.5 events and PTB, similar to the finding that only in high-BC regions did PM2.5 events remain associated with GDM and PTB. Mediation analyses in both the MR and cohort study suggest that GDM mediated the PM2.5 effect on PTB. Differences in key PM2.5 constituent(s) could help explain the causal association between PM2.5, GDM, and PTB. Women with GDM require more attention to prevent the transmission of PM2.5-related adverse effects from mothers to infants.

Seminal vesicle integrity supports semen composition and sperm function, whereas type 2 diabetes mellitus can induce atrophy and fibrosis in this organ. Using a high-fat diet/streptozotocin-induced model in male mice and primary mouse seminal vesicle epithelial cells exposed to high glucose, we assessed fibrotic remodeling, lipid metabolism, PPARα/PGC-1α signaling, endoplasmic reticulum stress, and apoptosis through histological, biochemical, and lipidomic analyses. Diabetic seminal vesicles showed atrophy and fibrosis together with altered lipid profiles, free fatty acid accumulation, reduced PPARα/PGC-1α expression, and increased IRE1-associated stress and apoptosis. Levocarnitine attenuated these changes in vivo and reduced profibrotic responses in vitro. PPARα overexpression reproduced several protective effects, whereas IRE1 inhibition reduced stress-associated injury without restoring PPARα/PGC-1α signaling. These findings identify metabolic dysregulation and endoplasmic reticulum stress as associated features of diabetic seminal vesicle remodeling and support further evaluation of levocarnitine for diabetes-associated reproductive tract injury.

Objective: Current pharmacological treatments for prostate diseases are limited by poor drug penetration into the prostate and systemic adverse effects. This study evaluated whether a novel vas-deferens injection device could improve targeted delivery of levofloxacin to the prostate. Methods: Healthy adult male Sprague–Dawley rats received a single dose of levofloxacin by either intravenous administration (IV) or trans-vas-deferens administration using a novel disposable device (VS). Plasma and prostate samples were collected from 0.5 to 24 h and analyzed by LC-MS/MS. Iodixanol micro-CT imaging was used to visualize the local delivery pathway. Pharmacokinetic evaluation included observed composite-profile Cmax/Tmax, AUC0-24, and fT. Time-dependent tissue selectivity was evaluated through partial AUC analyses, prostate-to-plasma exposure ratios, and pointwise concentration ratios. A bioequivalence-style framework was applied to compare relative exposure parameters using geometric mean ratios (GMRs) with the 80.00–125.00% reference interval. Exploratory PK/PD evaluation combined literature-derived free-drug fractions (fut_plasma = 0.55, fut_prostate = 0.080) to estimate fAUC/MIC against representative uropathogens, supplemented by Monte Carlo simulation (n = 5000) to estimate probability of target attainment (PTA) at an fAUC/MIC ≥ 30 threshold. Results: Imaging confirmed selective distribution within the reproductive tract after vas-deferens delivery. In plasma, VS substantially reduced systemic exposure compared with IV: Cmax was 4.74 μg/mL (VS) versus 10.72 μg/mL (IV), and AUC0-24 was 15.47 versus 28.59 μg·h/mL. In the prostate, VS maintained comparable or numerically higher exposure: Cmax was 61.96 μg/g (VS) versus 52.02 μg/g (IV), and AUC0-24 was 235.77 versus 208.77 μg·h/g. The tissue distribution factor fT was substantially elevated in VS (2.26; 95% CI: 1.58–3.19) compared with IV (1.06; 95% CI: 0.89–1.30). Bioequivalence-style analysis demonstrated that plasma GMRs for AUC0-24 and Cmax fell well below 80%, confirming reduced systemic burden, while prostate GMRs were maintained, and the prostate-to-plasma AUC ratio GMR was increased. Time-dependent partial AUC analyses revealed that VS significantly elevated the prostate-to-plasma exposure ratio. PK/PD evaluation showed that at 24 h, prostate fAUC/MIC against Enterobacteriaceae (MIC = 0.5 μg/mL) was 37.7 (VS) versus 33.4 (IV), with corresponding PTA values of 97% and 94%, while plasma fAUC/MIC remained substantially lower in the VS group. Conclusions: Trans-vas-deferens administration of levofloxacin via a novel injection device effectively reduced systemic drug exposure while maintaining or enhancing prostate tissue concentrations, thereby widening the therapeutic window and reducing systemic drug exposure.

BackgroundVaricocele is a leading cause of male infertility, primarily due to oxidative stress. This study aimed to investigate the relationship between dietary intake of antioxidants and micronutrients and semen quality in men with varicocele-related infertility.MethodsA retrospective analysis was conducted on 380 men between January 2018 and December 2023. Dietary intake of Vitamin C, E, Zinc, Selenium, CoQ10, and L-carnitine was assessed using a validated food frequency questionnaire. Semen parameters and DNA Fragmentation Index (DFI) were compared among intake tertiles (T1–T3) using ANOVA and multivariable linear regression, with adjustments for age, BMI, and smoking status.ResultsA higher intake of antioxidants (T3) was found to be significantly associated with increased sperm concentration (38.79 vs. 33.70 million/ml, p < 0.001), total motility (51.09% vs. 46.00%, p < 0.001), and improved morphology (p < 0.001). Regression models indicated that Zinc and CoQ10 were strong predictors of concentration, while Vitamin E and L-carnitine significantly predicted progressive motility (p < 0.001). Interestingly, Vitamin C intake showed an inverse correlation with DNA fragmentation (β = −2.46, p < 0.001).ConclusionThe findings consistently show that higher intake of certain micronutrients is linked to better semen quality and lower DNA damage in men with varicocele. This underscores the importance of optimizing nutrition as a crucial approach in addressing infertility related to varicocele.

Background:Varicocele causes male infertility through its association with oxidative stress that damages sperm. Dietary antioxidants together with micronutrients help to lower oxidative stress while enhancing sperm production, but their impact on varicocele-related infertility remains to be proven. Methods:The researchers conducted a retrospective cohort study of 900 men with varying degrees of varicocele, including 300 with Grade I, 400 with Grade II, and 200 with Grade III. The study collected data on participants' demographics, body measurements, daily habits, food consumption, micronutrient levels, oxidative stress indicators, antioxidant enzyme activity, reproductive hormone levels, semen characteristics, and reproductive success. The study used multiple linear and logistic regression analyses to identify factors affecting sperm concentration and motility, DNA fragmentation, and spontaneous conception. The researchers used standardized beta coefficients to quantify the contribution of each main predictor variable to the results. Results:The negative effects on sperm concentration and motility are attributable to varicocele severity, age, BMI, smoking, reactive oxygen species (ROS), and malondialdehyde (MDA), which generate DNA fragmentation, thereby establishing statistical significance at p < 0.05. The dietary antioxidants vitamin C, vitamin E, zinc, and selenium had positive effects on sperm concentration (β = 0.09-0.18) and motility (β = 0.10-0.16), while they had negative effects on DNA fragmentation (β = -0.07 to -0.15). The regression models explained 40-42% of the variability in sperm parameters. The logistic regression analysis found that antioxidant consumption increased the probability of natural conception (OR 1.05-1.13, p < 0.01), whereas age, BMI, varicocele degree, smoking, and ROS and MDA reduced the probability of conception (OR 0.64-0.97, p < 0.05). Clinical outcomes tracked 30% of participants who achieved natural conception, while 25% underwent assisted reproductive technology (ART) cycles, and the group attained a live birth rate of 28%. The group with Grade I varicocele and higher antioxidant intake showed improved outcomes. Conclusion:Men with varicocele demonstrated impaired sperm quality and reduced fertility potential, which appeared to be associated with increased oxidative stress and alterations in antioxidant status. The findings also suggest that lifestyle and dietary antioxidant intake may play a contributory role in modulating these effects.

During spermiogenesis, nuclear remodeling occurs where histones are sequentially replaced by transition proteins (TNPs) and protamines, a process essential for sperm maturation. Although the degradation of histones and TNPs is thought to be essential for sperm nuclear remodeling, the underlying mechanisms, particularly those governing TNP degradation, remain poorly understood. In this study, we investigated the role of the ankyrin repeat-containing SOCS box protein 9 (ASB9) during spermiogenesis and found that its deficiency causes TNP2 retention, leading to a failure of the histone-to-protamine transition in both humans and mice. This disruption consequently causes male infertility, characterized by sperm head malformation and impairments in fertilization and early embryonic development. Mechanistically, we found that ASB9 assembles a testis-specific Cullin-RING ligase (CRL) complex-TNP2-ASB9-ELOB/C-CUL5-RBX1-that mediates the ubiquitin-dependent degradation of TNP2 to facilitate the histone-to-protamine transition during spermiogenesis. Collectively, our study uncovers the mechanism underlying TNP2 degradation and highlights the critical role of ASB9 in male fertility through the CRL complex-mediated ubiquitination pathway, thereby expanding the fundamental understanding of nuclear remodeling during spermiogenesis.

To study the effects of L-carnitine and fructose on semen parameters of severe asthenospermia patients by sperm culturing in vitro within 24h. We optimized the energy composition and antioxidant substances of sperm culture medium in vitro (based on Ham's F10 culture medium) by orthogonal test for preparing high quality culture medium. Sperms of 60 patients with idiopathic severe asthenospermia were collected, and cultured in vitro within 24h, by Ham's F10 culture medium added to different concentrations of L-carnitine and fructose and culture temperature, whose effects on sperm motility were observed to determine which is the most appropriate concentration and temperature. For determining the appropriate concentration of L-carnitine and fructose and the suitable culture temperature in Ham's F10 culture medium, the orthogonal experiments were carried out to optimize above three factors, which had great influence on sperm viability, survival rate, deformity rate and DNA fragmentation index (DFI). The final concentration of L-carnitine and fructose was determined in terms of initial tests to assess the effects of different concentrations (4, 8, 12, and 16 mg/ml L-carnitine and 0.125, 0.250, 0.375, and 0.50 mg/ml fructose) on sperm viability and motility in culture. During the operation of processing and culturing sperms in vitro within 24h, orthogonal test showed that sperm viability was better at the final concentration of 8 mg/ml L-carnitine and 0.375 mg/ml fructose in improved Ham's F10 culture medium at 36.5°C. Idiopathic severe asthenospermia sperm can be effectively improved by the modified Ham's F10 culture medium of the final concentration of 8 mg/ml L-carnitine and 0.375 mg/ml fructose at 36.5°C within 24h, which has shown better culture effect and is superior to Ham's F10 basic medium.

BACKGROUND:High serum homocysteine (Hcy) levels are associated with reduced fertility and adverse pregnancy outcomes. Previous studies have produced inconsistent results regarding the influence of Hcy levels on in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcomes. Moreover, most existing studies have predominantly focused on Hcy levels in women, with limited attention given to serum Hcy levels in men. METHODS:This retrospective cohort study was conducted at the Reproductive Center of Xi'an People's Hospital (Xi'an Fourth Hospital) from October 2021 to October 2023, involving a total of 481 patients who underwent fresh embryo transfer. Male and female patients were grouped according to quartiles of serum Hcy concentration. Of these, 290 patients achieved pregnancy, while 191 did not. Follow-up data showed that 250 patients maintained their pregnancies to 12 weeks, while 40 experienced early miscarriage. Pregnancy outcomes were analyzed for all patients and for clinically pregnant women who were followed up to 12 weeks, with a focus on factors associated with early miscarriage. RESULTS:The results demonstrated that the pregnancy rate with female serum Hcy concentrations ≥ 12.43 µmol/L was significantly lower than in those with Hcy concentrations < 8.07 µmol/L (P = 0.006) and 8.07-9.57 µmol/L (P = 0.008). Female serum Hcy ≥ 12.43 µmol/L was identified as an independent risk factor for early miscarriage (OR = 2.20, 95 % CI 1.24-3.88). No significant correlation was observed between female serum Hcy levels and embryo quality. Additionally, there was no significant association between male serum Hcy levels and clinical pregnancy, pregnancy outcomes, or embryo quality. Among the 250 cases of clinical pregnancy, 97.6 % (244 cases) resulted in successful live births, while 2.4 % (6 cases) did not result in live births. Non-live birth cases were primarily attributed to factors such as premature rupture of membranes, cervical insufficiency, oligohydramnios, fetal abnormalities, and other causes. CONCLUSION:Elevated serum Hcy concentrations in women adversely affected clinical pregnancy and early miscarriage (≥12.43 µmol/L), while male serum Hcy did not show a significant effect. The inclusion of Hcy levels in both men and women provides a more comprehensive perspective for exploring multidimensional factors influencing fertility outcomes.

This study aims to investigate the trends in sperm concentration among fertile Chinese males over the past four decades, addressing whether there has been a change in sperm concentration and identifying potential causes. The research included 94 Chinese and English literature sources, covering 27 provinces and cities across China, encompassing a total of 14,634 individuals. A least squares linear regression model was applied to analyze sperm concentration data. The analysis indicated a significant downward trend overall from 1984 to 2023 (P = 8.42e − 10). A single-factor analysis of variance was performed, categorized by the year of sample collection, showing a decline in sperm concentration across each decade of the collection years (P = 1.01e − 08), with the most significant decline noted between 2004 and 2013 (P = 0.0035). The findings suggest a general decline in sperm concentration among fertile Chinese males over the past forty years, with a more pronounced decline after the twenty-first century, potentially associated with escalating environmental pollution due to heavy industrialization, poor lifestyle habits, and radiation from electronic devices. Further research is essential to elucidate the causes of and broader implications associated with this downward trend.

Early life, including the embryonic period, is particularly vulnerable to environmental exposures. Previous studies have largely focused on the relationship between individual environmental factors and population health. In reality, individuals are exposed to multiple environmental factors, which together form an "exposome" that reflects the environmental influences on human health. Exposome-based analyses utilizing biological samples have been conducted in various countries to assess the impacts of environmental endocrine disruptors and other pollutants on maternal and fetal health during pregnancy, particularly in developed countries. However, large-scale cohort studies that comprehensively cover major maternal and fetal diseases during pregnancy to explore the environmental and genetic interactions affecting maternal and fetal health are still lacking in China. Currently, environmental exposure assessment and biomarker measurement are particularly complex, given the challenges posed by handling mixed exposure effects and the hidden threats posed by emerging contaminants. The China Birth Cohort-Environmental Genetic Factors (CBC-EG) study was established as a large, multicenter cohort study spanning 14 cities across China. A total of 101,437 pregnant women were recruited between 2013 and 2022. The objectives of this cohort study include analyzing the effects of environmental exposure levels and behavioral factors, monitored through external exposure assessments, on embryonic development and pregnancy-related diseases. Additionally, the study aims to explore the impact of environmental pollutants, monitored through internal exposure assessments, on embryonic development and pregnancy outcomes. A key focus of this research is to investigate the potential threats posed by emerging contaminants to maternal and fetal health, as well as to uncover environmental and genetic interactions and identify susceptibility loci.

Multimodal precision nursing intervention enhances cognitive function and quality of life through multisensory collabo-rative stimulation by integrating multidimensional data of patients.As one of the most common complications after radical prostatecto-my,urinary incontinence seriously affects the quality of life of prostate cancer patients after surgery which has a negative impact on multidimensional health in the"physiological-psychological-social"aspects.This paper summarizes the clinical manifestations,influ-encing factors,and nursing interventions of urinary incontinence after radical prostatectomy,and focuses on the key points of nursing based on multimodal theory,in order to provide nursing strategies for improving urinary incontinence after prostate cancer surgery.

Gestational diabetes mellitus (GDM) is associated with mitochondrial dysfunction. Mitochondrial DNA (mtDNA) plays a critical role in mitochondrial function, affecting cellular oxidative phosphorylation and ATP supply. This study aims to explore the association between mtDNA variations and GDM in Han Chinese women. This nested case-control study was conducted among 701 women who developed GDM and 859 contemporaneous controls based on the Chinese Birth Cohort of Environmental and Genetic Factors between 2018 and 2022. Next-generation sequencing was performed on the samples to detect variations in the whole mitochondrial genome. The sequencing data were analyzed, and the differences in the number of mtDNA variations between the two groups were assessed using a t-test. Haplogroup analysis was conducted through the chi-square test. Logistic regression analysis was performed, adjusting for age, BMI, gravidity, and parity, to identify significantly different mtDNA variations between the two groups. Pregnant women with GDM carried fewer mtDNA variants in the D-loop region (11.35 ± 2.77 vs. 11.80 ± 2.86, p = 0.002). Results indicated that m.73A>G (OR: 0.46, 95

Type-2 diabetes mellitus (T2DM) is a complex metabolic disorder that adversely affects various physiological systems, particularly male reproductive health. Research indicates that T2DM increases the risk of retrograde ejaculation, impairing sexual function and fertility. Dysregulation of lysyl oxidase (LOX) has been linked to diabetes-related complications in the male reproductive system. However, its role in seminal vesicle remains unclear. This study investigates LOX’s involvement in diabetes-related seminal vesicle pathology using human and mouse models. We assessed LOX expression in the seminal vesicles of men with T2DM and created a T2DM mouse model to observe changes. Our findings revealed elevated LOX expression in the seminal vesicles of T2DM men, accompanied by epithelial atrophy and fibrosis. Similarly, T2DM mice displayed significant atrophy and fibrosis of the seminal vesicles, correlated with increased LOX levels. Treatment with the LOX inhibitor, β-aminopropionitrile (BANP), significantly improved extracellular matrix remodeling and normalized the architecture of the seminal vesicles. Besides, LOX inhibition led to a significant reduction in T lymphocyte infiltration and apoptosis in the seminal vesicle epithelium of T2DM mice.These results highlight LOX’s critical role in seminal vesicle fibrosis associated with T2DM. Targeting LOX may provide a promising therapeutic strategy to alleviate reproductive complications and preserve reproductive health in men with T2DM.

Objective:To evaluate the efficacy and safety of denosumab in the treatment of prostate cancer with bone metastases.Methods:Relevant studies were retrieved from PubMed,EMBASE,Cochrane,Web of Science,Sinomed,CNKI and Wanfang data-bases.The Cochrane risk-of-bias assessment tool was used to evaluate the quality of included studies,and relevant data were extracted.meta-analysis was performed using RevMan 5.4 and RStudio software,and forest plots were generated.Results:Six randomized con-trolled trials(RCTs)were included.Compared with the control group,denosumab significantly reduced the risk of skeletal-related e-vents(HR=0.78,95％CI:0.62-0.93).In terms of safety,denosumab did not increase the risk of total adverse events,severe adverse events and the adverse events higher than CTC grade 3.Conclusion:Denosumab can delay the time to first skeletal-related event with good safety.However,due to the limitations of this study,further high-quality,large-sample,multicenter RCTs are needed to confirm these findings.

Miao medicine is guided by the medical theories of the Miao ethnic group, and the drugs used by the Miao people are derived from natural plants and animals for the prevention and treatment of diseases and protection of health. In recent years, a large number of clinical studies have shown good clinical efficacy of traditional Miao medicine in the treatment of prostatic diseases, with the advantages of easy availability, low price, and minimal adverse reactions. However, currently no systematic literature review has been reported on the treatment of prostatic diseases with Miao medicine. This article focuses on the commonly used Miao drugs recorded in the Chinese Materia Medica－Miao Medicine, with a systematic review of relevant literature retrieved on the treatment of prostate diseases with Miao medicine in recent years and a summarization of the advances in the studies of its pharmacological effects, mechanisms of action and clinical application, aiming to provide some new perspectives and ideas for further academic research and clinical development of Miao medicine.

OBJECTIVE:The aim of this study is to evaluate the clinical efficacy of Oxalicao Formula combined　with transacupuncture in the treatment of chronic nonbacterial prostatitis （CNP）characterized by dampness-heat stasis. METHODS:A total of 70 patients diagnosed with CNP and characterized by dampness-heat stasis were randomly divided into control group and treatment group, with 35 cases in each group. The patients in control group received Qianlie Beixi capsules． Ｗhile the patients in　treatment group were administered with oxalis decoction in conjunction with acupuncture therapy　which lasted for 8 weeks. Pre- and post-treatment evaluations for NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), Traditional Chinese Medicine (TCM) symptom scores, urodynamic parameters, immune cell subsets and inflammatory factors were performed. RESULTS:Ultimately, 65 patients completed the study　with 33 in the treatment group and 32 in the control group. After 8 weeks of intervention, The patients in both of groups demonstrated significant improvements (P<0.05). Specifically, remarkable reductions in the NIH-CPSI total score　including pain score, urination score, quality of life impact score, TCM symptom score and inflammatory cytokine levels　were observed. Additionally, there were upward trend　in maximum and average urinary flow rates as well as the CD4+/CD8+ ratio of immune cells(P<0.05). Compared to the control group, the treatment group exhibited superior outcomes in reducing the NIH-CPSI total score, pain score, urination score, quality of life impact score, TCM symptom score, and inflammatory cytokine levels, and increasing in　CD4+/CD8+ ratios， maximum and average urine flow rates(P<0.05). CONCLUSION:The combination of Oxalicao Formula and transacupuncture for treating CNP characterized by dampness-heat stasis demonstrates significant therapeutic benefits, which has considerable clinical application value.

Objective:To assess the safety,efficacy and potential impact of stem cell therapy(SCT)in improving erectile dys-function(ED).Methods:A comprehensive search strategy was used to search the literatures on safety and efficacy evaluation of stem cell(SC)in the treatment of ED by human clinical trials from PubMed,Embase and Web of science databases with a search time frame from database creation to July 4,2024.The exclusion criteria were as follows:reviews,conference abstracts,animal experi-ments,and duplicate sample literature.Results:The study initially screened 1 773 papers,and 17 were included in the final analy-sis.These studies involved a total of 269 ED patients,and a variety of sources of stem cells had been used in the treatment of ED,in-cluding adipose-derived stem cells,bone marrow-derived stem cells,placental stroma-derived stem cells,umbilical cord-derived stem cells,dental pulp-derived stem cells,and oral mucosa-derived stem cells.All studies were conducted by injecting stem cells into the cavernous body of the penis,but there is no fixed standard for the amount of injection,injection site and number of injections.The op-timal treatment mode was still being explored.Patients' International Index of Erectile Function(IIEF)scores and Erection Hardness Score(EHS),peak systolic velocity(PSV),and end diastolic velocity(EDV)improved after treatment.But some studies showed that the efficacy of the treatment diminished with increasing time.No serious adverse effects were reported in any of the studies and none of the adverse effects persisted for a long period of time.The most common adverse effects included injection site reactions,and SCT showed a good safety and tolerability profile.Conclusion:SCT has the potential to be a promising and innovative regenerative therapy option for ED patients.In the future,with the advancement of stem cell technology,larger randomized controlled studies should continue to be conducted to explore standardized treatments,so as to further evaluate the long-term efficacy and safety of SCT for ED.

Aim: This study aims to investigate the association of the genetic variations in IGF2BP2 and CAPN10 as well as gene-environment interactions with the risk of gestational diabetes (GDM) in Chinese women. Materials and Methods: A total of 1,566 pregnant Chinese women participated in this case-control study. We employed targeted next-generation sequencing to analyze specific SNPs in IGF2BP2 (rs11927381, rs1470579, rs4402960, rs7640539) and CAPN10/rs2975760. Various genetic models were used to assess the associations of these polymorphisms with GDM risk. Gene-gene and gene-environment interactions were examined using GMDR to identify interaction models, Subsequently, logistic regression was employed to confirm the significance of these models and to evaluate their impact on GDM susceptibility. Results: Our study identified significant associations between the C allele of IGF2BP2/rs11927381 and an increased GDM susceptibility in both dominant (P = 0.031, OR = 1.247) and heterozygote (P = 0.043, OR = 1.239) gene models. Conversely, the heterozygote TC genotype of CAPN10/rs2975760 was associated with a reduced risk of GDM (P = 0.046, OR = 0.766). Increased BMI and O3 levels were linked to a higher GDM susceptibility. We discovered interactions between CAPN10/rs2975760 CC and IGF2BP2/rs11927381 TC genotype that exacerbated GDM risk (P = 0.022, OR = 11.337). Furthermore, interactions between IGF2BP2/ rs11927381 and environmental factors were observed, indicating increased GDM risks (BMI: P = 0.004, OR = 1.011; O3: P = 0.013, OR = 1.002; PM2.5: P = 0.042, OR = 1.005;BC: P = 0.048, OR = 1.094; NO3-:P = 0.045, OR = 1.024). Conclusion: GDM is significantly associated with IGF2BP2/rs11927381 and CAPN10/rs2975760 polymorphisms as well as exposure to O3. Furthermore, the interaction between the CAPN10/rs2975760 CC genotype and IGF2BP2/rs11927381 TC genotype, as well as environmental factors (O3, PM2.5, BMI), significantly increases the risk of GDM in Chinese women.