Cadmium（Cd） is a heavy metal that is harmful to human health. Early studies have shown that cadmium can damage testicular structure, affecting testosterone synthesis and spermatogenesis. However, the effect of paternal Cd exposure on the reproductive system of offspring remains unclear. In this study, male 8-week C57BL/6 J mice were used as research objects, and Cd was injected intraperitoneally every other day at a dose of 1 mg/kg for 5 weeks, after which the effect on the reproductive system of offspring male mice was studied. Our results showed that the body weight of the offspring male mice increased faster, with increases of the testicular and epididymis indices under Cd exposure. At the same time, the serum testosterone and free cholesterol decreased, total cholesterol increased, and the sperm concentration decreased. Further qRT-PCR and western blot analyses showed that the expressions of StAR, P450scc, 3β-HSD and 17β-HSD, which are related to testosterone synthesis, was significantly downregulated. Additionally, ATGL, LDLR and SR-BI, which are related to the intracellular cholesterol pool were downregulated, leading to the reduction of the cholesterol pool and the accumulation of lipid droplets. Oil red O and BODIPY staining revealed an increase in the abundance of lipid droplets in testicular tissue of newborn and adult mice. Prediction of tsRNA target genes in the sperm of parents and testicular transcriptome of newborn mice showed that the differentially expressed genes were associated with catabolism of fatty acids, cholesterol and ion channels, while the mitochondrial and lysosome functions of testicular tissue of adult offspring mice were decreased. Overall, our results suggest that paternal Cd exposure reduced the intracellular cholesterol pool of testicular of offspring, affected testosterone synthesis and reproductive system development.

Fetal ventriculomegaly (VM) is a common ultrasound finding with potential implications for pregnancy outcomes. There are few studies on the prevalence of genetic abnormalities in fetal VM. We aim to investigate the chromosomal and monogenic abnormalities risk and evaluate outcomes of fetal VM. We analyzed data from 211 pregnancies with fetal VM. Chromosomal abnormalities were assessed using karyotyping and/or CMA/CNV-Seq, and monogenic variations were detected through whole exome sequencing (WES) in cases with negative initial results. Pregnancy outcomes were also evaluated. The mean gestational age at VM detection was 27.0 weeks. Chromosomal abnormalities were detected in 13.3 % of cases overall, with a refined positive rate of 9.0 % after excluding polymorphisms and VUS CNVs. Subgroup analysis of 106 isolated VM cases revealed no significant differences in chromosomal abnormalities between unilateral and bilateral VM or between mild and moderate VM. Futhermore, 55 fetuses underwent WES, revealing pathogenic or likely pathogenic variants in 20 % of cases. Non-isolated VM cases showed a significantly higher rate of monogenic abnormalities (P = 0.01). Pregnancy outcomes indicated that isolated VM cases had a higher rate of normal development (89.2 %) compared to non-isolated cases (58.6 %), which also had higher rates of induced labor, stillbirths, and neonatal deaths. Ultrasound follow-up of 123 fetuses without chromosomal abnormalities showed that mild VM predominantly resolved or remained stable, while severe VM had a significantly higher progression rate compared to moderate VM. The study highlights the importance of distinguishing between isolated and non-isolated VM in prenatal diagnostics. Severe VM is associated with higher progression rates, while WES provides valuable insights into monogenic abnormalities, particularly in non-isolated cases. These findings underscore the need for comprehensive prenatal evaluation to better inform clinical decision-making and predict pregnancy outcomes.