The toxic effects and mechanisms of maternal exposure to Bisphenol F during gestation and lactation on lungs in female offspring mice.

Epidemiologic studies suggest that prenatal exposure to bisphenols may increase the risk of respiratory disease in children. Bisphenol F (BPF), a member of the bisphenol family, is widely used in industrial production. However, the potential pulmonary toxic effects and mechanisms of BPF exposure on offspring remain unclear. In this study, maternal mice were exposed to 0, 40, 400, and 4000 µg/kg BPF during gestation and lactation. The results showed that an inflammatory response was observed in lungs of BPF-exposed female offspring mice, characterized by peribronchial inflammatory cell infiltration and an increase in the number of inflammatory cells in BALF. Subsequent transcriptome analysis identified a total of 685 differentially expressed genes (DEGs) were in lungs of female offspring mice exposed to high-dose BPF, with 526 upregulated genes and 159 downregulated genes. Among upregulated DEGs of top 10, most of the upregulated genes were associated with inflammatory responses. In addition, enrichment analysis showed that immunosuppression and oxidative damage were significantly enriched in lungs of female offspring mice, suggesting that BPF could induce immunosuppression and oxidative stress in lungs of female offspring mice. Overall, our findings provide mechanistic insights into the potential pulmonary toxicity associated with BPF exposure during gestation and lactation.

Neurodevelopment effects of early life bisphenol-A exposure on visual memory: Insights into recovery dynamics.

Bisphenol A (BPA), a ubiquitous endocrine disruptor, is implicated in the cognitive deficits observed in both children and animals. Especially, BPA-induced spatial memory deterioration during the whole development phase of rodents has been well delineated. However, whether BPA exposure on the different development phases exerts similar effects on the prefrontal cortex (PFC) dependent visual memory is still elusive. Here, we chose two exposure windows, the whole gestation and lactation phases (E0∼P21) and the whole juvenile and adolescent phases (P22∼P60), for exposing rats to BPA. The visual memory of those rats was accessed by object recognition testing in the open field after BPA exposure and a constant recovery interval. The results revealed a substantial decline of visual memory under both exposure conditions, accompanied by an increase in anxiety-like behavior in BPA-exposed rats. Notably, after a 20-day recovery period, those behavioral changes induced by BPA exposure during P22∼60, not E0∼P21, were reversed compared to the control rats. According to morphological analysis of those rats after recovery, we found that the spine density of pyramidal neurons in the PFC were significant decreased in rats with BPA exposure during E0∼P21 and there was no difference between rats with or without BPA exposure during P22∼P60. Additionally, a similar change trend in excitatory receptors expression was observed under both exposure conditions. After an additional 20 days of recovery, the behavioral changes in rats with perinatal BPA exposure reverted to the normal status. Our present findings illuminate the dynamic effects of BPA on PFC-dependent functions across two crucial early developmental stages of life.

The Effects of Maternal Intake of EPA and DHA Enriched Diet During Pregnancy and Lactation on Offspring's Muscle Development and Energy Homeostasis.

EPA and DHA are n-3 long-chain polyunsaturated fatty acids with a diversity of health benefits on offspring. The objective of this study was to test the in vivo effect of maternal ingestion of EPA and DHA on fetal and offspring muscle development and energy balance. Two groups of female C57BL/6 mice were fed EPA and DHA enriched diet (FA) and diet devoid of EPA and DHA (CON) respectively throughout the entire period of gestation and lactation. Embryos at E13 and offspring at age of D1 and D21 were selected for sample collection and processing. No change in birth number and body weight were observed between groups at D1 and D21. Transient increase in the expression levels of myogenesis regulating genes was detected at D1 (p < 0.05) in FA group. Most of the expression of muscle protein synthesis regulating genes were comparable (p > 0.05) between FA and CON groups at D1 and D21. The significant increase in MHC4, and IGF-1 was not linked to increased muscle mass. A persistent increase in ISR expression (p < 0.05) but not in GLUT-4 (p > 0.05) was detected in offspring. Up-regulation of adipogenesis regulating genes was accompanied by increasing intramuscular fat accumulation in the offspring of FA group. Considerable increase in transcripts of genes regulating lipid catabolism and thermogenesis in liver (p < 0.05) was noticed in FA group at D21; whereas, only the levels of carnitine palmitoyl transferase 1A (Cpt1α) and Enoyl-CoA Hydratase And 3-Hydroxyacyl CoA Dehydrogenase (Ehhadh) increased at D1. Similarly, genes regulating lipolysis were highly expressed at D21 in FA group. EPA and DHA treatment promoted BAT development and activity by increasing the expression of BAT signature genes (p < 0.05). Also, maternal intake of EPA and DHA enriched diet enhanced browning of sWAT. Taken together, maternal ingestion of EPA/DHA may be suggested as a therapeutic option to improve body composition and counteract childhood obesity- related metabolic disorders and confer lifelong positive metabolic impact on offspring.

Exposure to Atrazine through gestation and lactation period led to impaired sexual maturation and subfertility in F1 male rats with congenital deformities in F2 progeny.

Several scientific reports suggest perturbed reproductive and developmental defects associated with environmental exposure to Atrazine (ATR). ATR has been associated with altered endocrine and reproductive functioning in-vivo exposed during the critical window of development. Thus, the present study investigates the effect of ATR exposure on F1-F2 male progeny exposed through gestation and lactation. F0 dams administered with ATR at doses 2, 10, 70, and 100 mg/kg b. wt/day from gestation day 6 to postnatal day 21. The F1 male rats were monitored for sexual maturation and subjected to fertility assessment on PND75. Delayed testicular descent was observed in 10, 70, and 100 mg/kg b. wt/day ATR dose with significantly lower serum testosterone, sperm count, and motility with testicular defects in F1 male. Expression of Androgen receptor (AR), Estrogen receptors (ER α and ER ß), StAR, Aromatase, and INSL-3 were upregulated at all doses indicating estrogenic/anti-androgenic activity of ATR. Fertility assessment revealed subfertility in F1 males with high (%) pre- and post-implantation loss at 10, 70, and 100 mg/kg b. wt/day dose as compared to control. Further, F2 fetuses exhibited congenital disabilities viz. decreased weight, crown-rump length, and anogenital distance with several other morphological deformities. To conclude, ATR exerted estrogenic and/or anti-androgenic activity with fetotoxic effects through the male germline.

Disruption of Bone Zinc Metabolism during Postnatal Development of Rats after Early Life Exposure to Cadmium.

This current study was conducted to investigate whether bone tissue impairment induced by early life exposure to cadmium (Cd) during postnatal development could result from disruption to zinc (Zn) metabolism. For this reason, the offspring from mothers receiving either tap water, Cd, Zn or Cd + Zn during gestation and lactation periods were euthanized at PND21 and PND70. At the end of the lactation period (PND21), our results showed that exposure to Cd increased Cd accumulation and Zn depletion in the femur. Furthermore, calcium (Ca) level was reduced. At the molecular level, Cd induced an increase of MT-1 expression and caused an upregulation of ZIP2 accompanied with a down-regulation of ZnT5. Runx2, ALP, colα-1 and Oc mRNA levels were also decreased. In plasma, IGF-1 and osteocalcin concentrations were decreased. Further, Cd altered femoral growth by generating changes in the growth plate. Consequently, the toxic effect of Cd persisted at adult age (PND70) by decreasing bone volume (%BV/TV), bone mineral density (BMD) and Ca content and by increasing trabecular separation (Tb.Sp) in the distal femur. Interestingly, Zn supply provided total or partial corrections of several toxic effects of Cd. These data suggest that the increases of Zn bioavailability as well as the reduction of Cd accumulation in the femur following the changes in ZIP2 and ZnT5 expression are part of the mechanism involved in Zn protection against Cd toxicity on bone tissue.

Dietary supplementation with garcinol during late gestation and lactation facilitates acid-base balance and improves the performance of sows and newborn piglets1.

The present study was conducted to evaluate the effects of dietary garcinol supplementation during late gestation (from the 90th day of pregnancy; day 90) and lactation on the acid-base balance of the umbilical cord blood and performance of sows and piglets. Sixty sows (Duroc × Yorkshire × Landrace; second- or third-parity; n = 20) were randomly divided into 3 gestation (day 90 of pregnancy) or lactation treatments, control diet (CON; basal diet), basal diet with 200 mg garcinol, and basal diet with 600 mg garcinol per kg of feed. The body weight (BW); backfat thickness and litter size of the sows; and birth weight, weaning weight, and mortality of piglets were recorded. Sows' blood and piglets' umbilical cord blood were collected for the measurements of hematological parameters and antioxidative and immune indexes, and acid-base balance parameters, respectively. The colostrum and milk and fecal samples of the sows were also collected for analysis of milk composition and apparent total tract nutrient digestibility. Garcinol had no effect on the BW and backfat thickness of the sows but significantly increased the birth weight and weaning weight of piglets (P < 0.05) and decreased the mortality (P < 0.05). Moreover, the white blood cell counts and neutrophil count, mean cell hemoglobin, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activity in the plasma of the sows were increased more significantly (P < 0.05) in the garcinol groups than that in the CON group, whereas the malondialdehyde (MDA) content was decreased (P < 0.05). The garcinol treatment significantly increased the pH, HCO3- and base excess values (P < 0.05), whereas it decreased the pCO2 and lactate content (P < 0.05) in the umbilical blood. Dry matter (DM), ash, and ether extract in the colostrum were similar between groups (P > 0.05), whereas the garcinol significantly increased the crude protein (CP) in the milk. In addition, the content of immunoglobulin A (IgA) and immunoglobulin G (IgG) in the plasma of piglets and in colostrum and milk of sows were increased more significantly (P < 0.05) in the garcinol groups than that in the CON group. The apparent total tract nutrient digestibility was similar between treatments. Collectively, this study indicates that sows fed with garcinol in late gestation and lactation showed improved maternal health and antioxidative status, milk protein content, acid-base balance in the umbilical cord blood, and growth performance in piglets, showing promise in natural plant extract nutrition for sows.

Maternal suppplementation with conjugated linoleic acid reduce anxiety and lipid peroxidation in the offspring brain.

BACKGROUND: Maternal consumption of fatty acids can alter neuronal membrane function, synaptic connections, and protect the brain from alterations caused by disturbances such as lipid peroxidation and anxiety in the offspring. We aimed to investigate how the maternal consumption of conjugated linoleic acid (CLA) interferes in anxiety behavior of the offspring and cerebral lipid peroxidation. METHODS: Three groups were formed: control (CG) - diet without CLA; CLA1 - diet containing 1% of CLA; and CLA3 - diet containing 3% of CLA. These diets were offered to the mothers from the 7th day of gestation until the end of lactation. The following behavioral tests were used: Elevated plus maze (EPM), Open Field (OF) and Light-dark Box (LDB). Levels of malondialdehyde (MDA) and glutathione were measured in the offspring's brains. Data were analyzed by ANOVA followed by the Holm-Sidak post-test or the Kruskal-Wallis test (p < 0.05). RESULTS: CLA1 and CLA3 showed higher number of entries in the open arms and time spent in the central area in EPM, they translocated and ambulated more in the clear area of the LDB and presented more rearing in the OF compared to CG (p < 0.05); moreover, they presented higher concentration of glutathione and lower MDA in brain tissue (p < 0.05). LIMITATIONS: We evaluated the effect of maternal consumption of CLA on anxiety and lipid peroxidation in rats' offspring, but a similar study should be performed in humans. CONCLUSIONS: Maternal intake of CLA induced a decrease in the parameters of anxiety and cerebral lipid peroxidation in the offspring.

Maternal fluoride exposure during gestation and lactation decreased learning and memory ability, and glutamate receptor mRNA expressions of mouse pups.

Previous investigations demonstrated that high fluoride (F) exposure may adversely affect the neurodevelopment and learning and memory ability. However, whether maternal F exposure during gestation and lactation can influence the learning, memory ability, and glutamate receptor expressions of offspring has not yet been elucidated. Hence, in the present study, maternal mice were exposed to F (25, 50, or 100 mg/L sodium fluoride (NaF) in drinking water) during gestation and lactation. Results showed that exposure to 100 mg/L NaF significantly enhanced the number of total arm entries and working memory errors of offspring in the radial arm maze test compared to the control group. However, no difference was observed in open-field behaviors. For the subtypes of glutamate receptors in hippocampus, expression of GluR2 mRNA was significantly reduced by 25, 50, and 100 mg/L NaF. Besides, F exposure also suppressed the expression of NR2A, NR2B, and mGluR2 mRNA levels in a dose-dependent manner, where NR2A was significantly suppressed by 50 mg/L NaF and NR2B and mGluR2 by 100 mg/L NaF. However, no significant changes were observed in GluR1 and mGluR5 mRNA expression levels. Collectively, these findings suggested that F can pass through the cord blood and breast milk and may have deleterious impact on learning and memory of the mouse pups, which was mediated by reduced mRNA expression of glutamate receptor subunits.

Involvement of testicular DAAM1 expression in zinc protection against cadmium-induced male rat reproductive toxicity.

In order to verify the effects of exposure to Cd and Zn on testicular DAAM1 gene and protein expression and also to ascertain their involvement in the protective role of Zn in prevent the testicular toxicity Cd-induced in male offspring rats at adult age after gestational and lactational exposure, male offspring rats, from mothers receiving either tap water, Cd, Zn, or Cd + Zn during gestation and lactation periods, were scarified on postnatal days (PND) 70. The reproductive organ (testis, epididymis, and vesicle seminal) were collected, weighed, and analyzed. The results showed that exposure to Cd in utero and through lactation decreased the relative reproductive organ weight, altered the testicular histology at the interstitial and tubular levels, and causing a significant reduction in the daily sperm production (DSP) per testis and per gram of testis, and other then altering the epididymal sperm quality. Furthermore, both mRNA and protein expression of rat testicular DAAM1 were also inhibited in Cd-treated group. Zn supply has completely corrected the most of these toxic effects. Our results imply that Zn could prevent Cd-induced testicular toxicity and sperm quality alteration in adult male rat after gestational and lactational exposure, probably via the restoration of the testicular DAAM1 expression inhibited by Cd.

Changes in Liver Antioxidant Status of Offspring Mice Induced by Maternal Fluoride Exposure During Gestation and Lactation.

Excessive fluoride intake for a long time has been demonstrated to provoke hepatic oxidative stress in adults. However, the response to fluoride toxicity of liver in newborns exposed to fluoride during embryonic and suckling stages remains unclear. In this study, female Kunming mice were administrated with 25, 50, and 100 mg/L sodium fluoride (NaF) from prenatal day 0 to day 21 after delivery, and the antioxidative status in the liver of their pups at postnatal day 21 was evaluated. The results showed that compared with the control group, NaF significantly increased malondialdehyde (MDA) level and reduced catalase (CAT) activity, while no statistical difference was observed in activities and mRNA expressions of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR). Notably, with comparison to the controls, the protein level of CAT was significantly reduced in medium- and high-fluoride groups, while its relative mRNA abundance was enhanced which could result from the encouragement of the lowered CAT protein expression. These findings suggested that CAT was more susceptible to low-fluoride exposure in early life.