Exposure to ubiquitous plastic-associated endocrine disrupting chemicals (EDCs) is associated with the increased risk of many chronic diseases. For example, phthalate exposure is associated with cardiometabolic mortality in humans, with societal costs ~ $39 billion/year or more. We recently demonstrated that several widely used plastic-associated EDCs increase cardiometabolic disease in appropriate mouse models. In addition to affecting adult health, parental exposure to EDCs has also been shown to cause metabolic disorders, including obesity and diabetes, in the offspring. While most studies have focused on the impact of maternal EDC exposure on the offspring’s health, little is known about the effects of paternal EDC exposure. In the current study, we investigated the adverse impact of paternal exposure to a ubiquitous but understudied phthalate, dicyclohexyl phthalate (DCHP) on the metabolic health of F1 and F2 offspring in mice. Paternal DCHP exposure led to exacerbated insulin resistance and impaired insulin signaling in F1 offspring without affecting diet-induced obesity. We previously showed that sperm small non-coding RNAs including tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs) contribute to the intergenerational transmission of paternally acquired metabolic disorders. Using a novel PANDORA-seq, we revealed that DCHP exposure can lead to sperm tsRNA/rsRNA landscape changes that were undetected by traditional RNA-seq, which may contribute to DCHP-elicited adverse effects. Lastly, we found that paternal DCHP can also cause sex-specific transgenerational adverse effects in F2 offspring and elicited glucose intolerance in female F2 descendants. Our results suggest that exposure to endocrine disrupting phthalates may have intergenerational and transgenerational adverse effects on the metabolic health of their offspring. These findings increase our understanding of the etiology of chronic human diseases originating from chemical-elicited intergenerational and transgenerational effects.

During field surveys and culture procedures, large growth disparities in Anguilla japonica have been observed. However, the potential causes are unknown. This study explored differences in digestive ability, metabolic levels, and transcriptomic profiles of appetite-related genes between growth-retarded eel (GRE) and normal-growing eel (NGE) under the same rearing conditions. The results showed that growth hormone (gh) mRNA expression in GREs was considerably lower than NGEs. The levels of total protein (TP), total cholesterol (T-CHO), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood ammonia (BA), blood urea nitrogen (BUN), and alkaline phosphatase (ALP) in GREs were significantly lower than in NGEs. Conversely, levels of glucose (GLU), alanine aminotransferase (ALT), and aspartate transaminase (AST) were higher in GREs. The activities of SOD, CAT, and T-AOC levels were also significantly lower in GREs, as were the activities of glucose-related enzymes including hexokinase (HK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6PASE). Additionally, orexigenic genes (npy and ghrelin) were dramatically downregulated, whereas anorexigenic genes (crh and pyy) were significantly upregulated in GREs. These findings suggested that variances in growth hormone, metabolic activities, and appetite level could be associated with the different growth rates of A. japonica. The present research not only revealed the characteristics of the growth, metabolism, and appetite of GREs but also offered new perspectives into the substantial growth discrepancies in A. japonica, providing novel ideas for enhancing fish growth.

A high carbohydrate–low protein diet can induce hepatic global DNA hypomethylation in trout. The mechanisms remain unclear. We aimed to investigate whether an increase in dietary carbohydrates (dHCs) or a decrease in dietary proteins (dLPs) can cause hepatic global DNA hypomethylation, as well as explore the underlying mechanisms in trout. Two feeding trials were conducted on juvenile males, both of which involved a 4-d fasting and 4-d refeeding protocol. In trial 1, trout were fed either a high protein–no carbohydrate [HP-NC, protein 60% dry matter (DM), carbohydrates 0% DM] or a moderate protein–high carbohydrate (MP-HC, protein 40% DM, carbohydrates 30% DM) diet. In trial 2, fish were fed either a moderate protein–no carbohydrate (MP-NC, protein 40% DM, carbohydrates 0% DM), an MP-HC (protein 40% DM, carbohydrates 30% DM), or a low protein–no carbohydrate (LP-NC, protein 20% DM, carbohydrates 0% DM) diet to separate the effects of dHCs and dLPs on the hepatic methylome. Global C^mCGG methylation, DNA demethylation derivative concentrations, and mRNA expression of DNA (de)methylation-related genes were measured. Differences were tested by 1-factor ANOVA when data were normally distributed or by Kruskal–Wallis nonparametric test if not. In both trials, global C^mCGG methylation concentrations remained unaffected, but the hepatic 5-mdC content decreased after refeeding (1–3%). The MP-HC group had 3.4-fold higher hepatic 5-hmdC and a similar 5-mdC concentration compared with the HP-NC group in trial 1. Both MP-HC and LP-NC diets lowered the hepatic 5-mdC content (1–2%), but only the LP-NC group had a significantly lower 5-hmdC concentration (P < 0.01) compared with MP-NC group in trial 2. dHC and dLP independently induced hepatic global DNA demethylation in trout. The alterations in other methylation derivative concentrations indicated the demethylation process was achieved through an active demethylation pathway and probably occurred at non-C^mCGG sites.

Significant growth heterogeneity is prevalent in farmed Japanese eels ( Anguilla japonica ), whereas its underlying causes remain poorly understood. The study investigated the metabolic, digestive, and behavioral phenotypic differences between fast‐ and slow‐growing A. japonica . A total of 100 elvers (22.88 ± 1.11 g) were randomly allocated into four net cages (25 individuals per cage). After 8 weeks of rearing, the three heaviest and three lightest individuals from each cage were selected and designated as fast‐growing eel (FGE) and slow‐growing eel (SGE), respectively. Plasma metabolic profiling revealed that SGE showed significantly lower levels of total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C) and lactate compared to FGE, while aspartate aminotransferase (AST) was higher ( p < 0.05). Moreover, oxygen consumption rate (OR) and ammonia excretion rate (AR) in SGE were significantly higher than FGE. Significant differences in digestive and metabolic enzyme activities were observed, with SGE displaying lower amylase, trypsin, Na ⁺ ‐K ⁺ ‐ATPase, and ATPase levels than FGE ( p < 0.05). In behavioral phenotypes, SGE exhibited a longer latency time, along with reduced total feed intake and amount of feces than FGE, while no significant differences in relative feed intake or relative amount of feces. Additionally, compared to FGE, the expression levels of neuropeptide Y ( npy ) and ghrelin were significantly downregulated in SGE, whereas corticotropin‐releasing hormone ( crh ) mRNA upregulated ( p < 0.05). Multivariate analysis identified that AST and crh may serve as primary discriminators for SGE classification. In conclusion, the differences in feeding behavior, metabolic level, and digestive capacity were related to growth disparity between individual eels. These findings advanced our mechanistic understanding of growth variation in A. japonica and provided valuable insights for promoting uniform growth.

The gonadal development of Japanese eels (Anguilla japonica) plays a crucial role in the success of artificial breeding. Soy isoflavones, a class of phytoestrogens commonly found in aquafeeds, have shown potential in enhancing gonad development in fish. The present study evaluated the effects of dietary soy isoflavones on gonadal development, growth performance, histology, sex hormone levels, vitellogenin content, and expression of related genes in female Japanese eel broodstock. A 4-week feeding trial was conducted with 120 two-year-old female eels randomly assigned to four groups and fed diets containing 0 (C), 0.1 (L), 0.5 (M), and 0.9 (H) mg/g of soy isoflavones. The results indicated that gonadal development was enhanced in the M and H groups, as evidenced by a significantly higher gonadosomatic index (GSI) and increased oocyte cross-sectional area (CSA) in M group, and greater nutrient accumulation in both the M and H groups. The expression of er and cyp19a genes in the ovary was downregulated in the treatment groups, leading to decreased serum estradiol (E2) and increased testosterone levels. Furthermore, hepatic vtg gene expression was upregulated in the M and H groups, though VTG protein content remained unchanged, suggesting an initiation of vitellogenesis at the transcriptional level. In conclusion, dietary soy isoflavones at 0.5–0.9 mg/g provide an effective pretreatment strategy to enhance early ovarian development in Japanese eel broodstock, potentially improving their responsiveness to subsequent hormonal induction in artificial breeding programs.