scholarly journals Maternal folic acid supplementation does not counteract the deleterious impact of prenatal exposure to environmental pollutants on lipid homeostasis in male rat descendants

2019 ◽  
Vol 11 (4) ◽  
pp. 427-437 ◽  
Author(s):  
Pauline Navarro ◽  
Mathieu Dalvai ◽  
Phanie L. Charest ◽  
Pauline M. Herst ◽  
Maryse Lessard ◽  
...  
Keyword(s):  
Folic Acid ◽  
Prenatal Exposure ◽  
Corn Oil ◽  
Plasma Cholesterol ◽  
Lipid Homeostasis ◽  
Male Rat ◽  
Epididymal Adipose Tissue ◽  
Paternal Lineage ◽  
Hepatic Lipids ◽  
Offspring Health

AbstractPrenatal exposure to persistent organic pollutants (POPs) has been associated with the development of metabolic syndrome-related diseases in offspring. According to epidemiological studies, father’s transmission of environmental effects in addition to mother’s can influence offspring health. Moreover, maternal prenatal dietary folic acid (FA) may beneficially impact offspring health. The objective is to investigate whether prenatal FA supplementation can overcome the deleterious effects of prenatal exposure to POPs on lipid homeostasis and inflammation in three generations of male rat descendants through the paternal lineage. Female Sprague-Dawley rats (F0) were exposed to a POPs mixture (or corn oil) +/− FA supplementation for 9 weeks before and during gestation. F1 and F2 males were mated with untreated females. Plasma and hepatic lipids were measured in F1, F2, and F3 males after 12-h fast. Gene expression of inflammatory cytokines was determined by qPCR in epididymal adipose tissue. In F1 males, prenatal POPs exposure increased plasma lipids at 14 weeks old and hepatic lipids at 28 weeks old and prenatal FA supplementation decreased plasma total cholesterol at 14 weeks old. Prenatal POPs exposure decreased plasma triglycerides at 14 weeks old in F2 males. No change was observed in inflammatory markers. Our results show an impact of the paternal lineage on lipid homeostasis in rats up to the F2 male generation. FA supplementation of the F0 diet, regardless of POPs exposure, lowered plasma cholesterol in F1 males but failed to attenuate the deleterious effects of prenatal POPs exposure on plasma and hepatic lipids in F1 males.

scholarly journals Prenatal Exposure to Persistent Organic Pollutants and Maternal Folic Acid Supplementation: Their Impact on Glucose Homeostasis in Male Rat Descendants

Environments ◽  
2021 ◽  
Vol 8 (3) ◽  
pp. 24
Author(s):  
Pauline Navarro ◽  
Mathieu Dalvai ◽  
Phanie L. Charest ◽  
Pauline M. Herst ◽  
Maryse Lessard ◽  
...  
Keyword(s):  
Folic Acid ◽  
Organic Pollutants ◽  
Prenatal Exposure ◽  
Glucose Homeostasis ◽  
Persistent Organic Pollutants ◽  
Corn Oil ◽  
Male Rat ◽  
Oral Glucose ◽  
Sprague Dawley ◽  
C Peptide

Exposure to persistent organic pollutants (POPs) is associated with insulin resistance while folic acid (FA) may offer a protective effect. However, the paternal contribution to metabolic phenotypes in offspring is not well known yet. Hence, we investigated whether maternal exposure to POPs affects glucose homeostasis and whether maternal FA supplementation counteracts POP effects transmitted via male descendants. Sprague–Dawley founder dams (F0) were fed a diet containing 2 or 6 mg/kg of FA and were force-fed with either a POP mixture or corn oil for 9 weeks. Subsequent male descendants did not receive any treatment. Blood glucose, plasma insulin and C-peptide were measured during an oral glucose tolerance test in males aged 90 and 180 days from generation 1 (F1), 2 (F2) and 3 (F3). Prenatal POP exposure increased fasting glucose in 90-day-old F1 males and C-peptide in 90-day-old F2 males. Prenatal FA supplementation decreased C-peptide in 90 and 180-day-old F1 males. In 180-day-old F3 males, FA supplementation counteracted POPs on fasting and postglucose C-peptide, indicating reduced insulin secretion. Prenatal exposure to an environmentally relevant POP mixture caused abnormalities in glucose homeostasis that are transmitted from one generation to the next through the paternal lineage. Prenatal FA supplementation counteracted some of the deleterious effects of POPs on glucose homeostasis.

scholarly journals Prenatal Exposure to Environmentally-Relevant Contaminants Perturbs Male Reproductive Parameters Across Multiple Generations that are Partially Protected by Folic Acid Supplementation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Maryse Lessard ◽  
Pauline M. Herst ◽  
Phanie L. Charest ◽  
Pauline Navarro ◽  
Charles Joly-Beauparlant ◽  
...  
Keyword(s):  
Folic Acid ◽  
Prenatal Exposure ◽  
Pregnancy Outcomes ◽  
Corn Oil ◽  
Sperm Quality ◽  
Male Reproduction ◽  
Female Rats ◽  
Sperm Parameters ◽  
Multiple Generations ◽  
The Impact

Abstract The paternal environment is thought to influence sperm quality and future progeny may also be impacted. We hypothesized that prenatal exposure to environmentally-relevant contaminants impairs male reproduction, altering embryo gene expression over multiple generations. Folic acid (FA) can improve sperm quality and pregnancy outcomes, thus we further hypothesized that FA mitigates the contaminants. Sprague-Dawley F0 female rats treated with persistent organic pollutants (POPs) or corn oil and fed basal or supplemented FA diets, then used to yield four generations of litters. Only F0 females received POPs and/or FA treatments. In utero POPs exposure altered sperm parameters in F1, which were partly rescued by FA supplementation. Paternal exposure to POPs reduced sperm quality in F2 males, and the fertility of F3 males was modified by both POPs and FA. Ancestral FA supplementation improved sperm parameters of F4 males, while the POPs effect diminished. Intriguingly, F3 males had the poorest pregnancy outcomes and generated the embryos with the most significantly differentially expressed genes. Early-life exposure to POPs harms male reproduction across multiple generations. FA supplementation partly mitigated the impact of POPs. The two-cell embryo transcriptome is susceptible to paternal environment and could be the foundation for later pregnancy outcomes.

scholarly journals Maternal Folic Acid Impacts DNA Methylation Profile in Male Rat Offspring Associated With Neurodevelopment and Learning/Memory Abilities

2020 ◽  
Author(s):  
Xinyan Wang ◽  
Zhenshu Li ◽  
Yun Zhu ◽  
Jing Yan ◽  
Huan Liu ◽  
...  
Keyword(s):  
Folic Acid ◽  
Gene Network ◽  
Underlying Mechanism ◽  
Male Rat ◽  
Methylated Dna ◽  
Rat Offspring ◽  
Kegg Pathway Analysis ◽  
Differentially Methylated Genes ◽  
Dna Methylation Profile ◽  
Gene Network Analysis

Abstract Background: Periconceptional folic acid (FA) supplementation not only reduces the incidence of neural tube defects, but also improves cognitive performances in offspring. However, the genes or pathways that are epigenetically regulated by FA in neurodevelopment were rarely reported. Methods: To elucidate the underlying mechanism, the effect of FA on the methylation profiles in brain tissue of male rat offspring was assessed by methylated DNA immunoprecipitation chip. Differentially methylated genes (DMGs) and gene network analysis were identified using DAVID and KEGG pathway analysis. Results: Compared with the FA-N group, 1939 DMGs were identified in the FA-D group, and 1498 DMGs were identified in the FA-S group, among which 298 DMGs were overlapped. The pathways associated with neurodevelopment and learning/memory abilities were differentially methylated in response to maternal FA intake during pregnancy, and there were some identical and distinctive potential mechanisms under FA deficiency or supplemented conditions. Conclusions: In conclusion, genes and pathways associated with neurodevelopment and learning/memory abilities were differentially methylated in male rat offspring in response to maternal FA deficiency or supplementation during pregnancy.

scholarly journals Folic acid supplementation reduces multigenerational sperm miRNA perturbation induced by in utero environmental contaminant exposure

2019 ◽  
Vol 5 (4) ◽  
Author(s):  
P M Herst ◽  
M Dalvai ◽  
M Lessard ◽  
P L Charest ◽  
P Navarro ◽  
...  
Keyword(s):  
Folic Acid ◽  
Target Genes ◽  
Corn Oil ◽  
System Development ◽  
Sex Differentiation ◽  
Control Diet ◽  
Folic Acid Supplementation ◽  
In Utero ◽  
Contaminant Exposure ◽  
Two Generations

Abstract Persistent organic pollutants (POPs) can induce epigenetic changes in the paternal germline. Here, we report that folic acid (FA) supplementation mitigates sperm miRNA profiles transgenerationally following in utero paternal exposure to POPs in a rat model. Pregnant founder dams were exposed to an environmentally relevant POPs mixture (or corn oil) ± FA supplementation and subsequent F1–F4 male descendants were not exposed to POPs and were fed the FA control diet. Sperm miRNA profiles of intergenerational (F1, F2) and transgenerational (F3, F4) lineages were investigated using miRNA deep sequencing. Across the F1–F4 generations, sperm miRNA profiles were less perturbed with POPs+FA compared to sperm from descendants of dams treated with POPs alone. POPs exposure consistently led to alteration of three sperm miRNAs across two generations, and similarly one sperm miRNA due to POPs+FA; which was in common with one POPs intergenerationally altered sperm miRNA. The sperm miRNAs that were affected by POPs alone are known to target genes involved in mammary gland and embryonic organ development in F1, sex differentiation and reproductive system development in F2 and cognition and brain development in F3. When the POPs treatment was combined with FA supplementation, however, these same miRNA-targeted gene pathways were perturbed to a lesser extend and only in F1 sperm. These findings suggest that FA partially mitigates the effect of POPs on paternally derived miRNA in a intergenerational manner.

scholarly journals Particulate Matter Exposure During Perinatal Life Results in Impaired Glucose Metabolism in Adult Male Rat Offspring

2018 ◽  
Vol 49 (1) ◽  
pp. 395-405 ◽  
Author(s):  
Rosiane Aparecida Miranda ◽  
Claudinéia Conationi da Silva Franco ◽  
Carina Previate ◽  
Vander Silva Alves ◽  
Flávio Andrade Francisco ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Air Quality ◽  
Glucose Metabolism ◽  
Urban Area ◽  
Corn Oil ◽  
Disease Incidence ◽  
Later Life ◽  
Male Offspring ◽  
Male Rat ◽  
Rat Offspring

Background/Aims: Particulate matter (PM) is an important risk factor for immunological system imbalance due to its small size, which can reach more distal regions of the respiratory tract, independently of its chemical composition. Some studies have suggested that PM exposure is associated with an increased incidence of diabetes, especially in industrialized urban regions. However, studies regarding the effects of PM exposure during perinatal life on glucose metabolism are limited. We tested whether exposure to PM from an urban area with poor air quality during pregnancy and lactation could cause short- and long-term dysfunction in rat offspring. Methods: Samples of < 10 µm PM were collected in an urban area of Cotonou, Benin (West Africa), and reconstituted in corn oil. Pregnant Wistar rats received 50 µg PM/day by gavage until the end of lactation. After birth, we analyzed the dams’ biochemical parameters as well as those of their male offspring at 21 and 90 days of age. Results: The results showed that PM exposure did not lead to several consequences in dams; however, the male offspring of both ages presented an increase of approximately 15% in body weight. Although the blood glucose levels remained unchanged, the insulin levels were increased 2.5- and 2-fold in PM exposure groups of both ages, respectively. HOMA-IR and HOMA-β were also increased at both ages. We also demonstrated that the number, islet area and insulin immunodensity of pancreatic islets were significantly increased at both ages from PM exposure. Conclusion: Our data show that chronic PM exposure by the oral route during perinatal life in rats leads to glucose dyshomeostasis in male offspring both in early and later life. Thus, we suggest that an ambience with poor air quality, mainly where traffic is dense, can contribute to an increase in metabolic disease incidence.

scholarly journals Postnatal Dietary Omega-3 Fatty Acid Supplementation Rescues Glucocorticoid-Programmed Adiposity, Hypertension, and Hyperlipidemia in Male Rat Offspring Raised on a High-Fat Diet

Endocrinology ◽  
2013 ◽  
Vol 154 (9) ◽  
pp. 3110-3117 ◽  
Author(s):  
Intan S. Zulkafli ◽  
Brendan J. Waddell ◽  
Peter J. Mark
Keyword(s):  
Blood Pressure ◽  
Fatty Acids ◽  
High Fat Diet ◽  
Plasma Cholesterol ◽  
Adverse Outcomes ◽  
Male Rat ◽  
Delayed Puberty ◽  
Adult Offspring ◽  
Omega 3 ◽  
High Fat

Fetal glucocorticoid excess programs several adverse outcomes in adult offspring, many of which can be prevented by postnatal, dietary omega-3 (n-3) fatty acids. Here we tested 2 separate hypotheses: 1) a postnatal high-fat diet exacerbates the glucocorticoid-programmed phenotype; and 2) postnatal, dietary n-3 fatty acids rescue programmed outcomes, even in the presence of a high-fat diet challenge. Pregnant Wistar rat dams were either untreated or administered dexamethasone acetate (Dex; 0.5 μg/mL drinking water) from day 13 of pregnancy. Offspring were cross-fostered to untreated mothers and males were weaned onto a standard (Std), high-fat, low n-3 (HF), or high-fat, high n-3 (HFHn-3) diet. Prenatal Dex reduced birth weight (26%) and delayed puberty onset by 1.2 days, irrespective of postnatal diet. Prenatal Dex programmed increased blood pressure in adult offspring, an effect worsened by the postnatal HF diet. Supplementation with high n-3 fatty acids, however, prevented both the Dex and HF-induced increases in blood pressure. Prenatal Dex also programmed increased adiposity, plasma cholesterol, and plasma triglyceride levels at 6 months of age, particularly in those offspring raised on the HF diet. But again, each of these adverse outcomes was rescued by supplementation of the HF diet with n-3 fatty acids. In conclusion, the capacity of n-3 fatty acids to overcome adverse programming outcomes remains evident, even in the presence of a HF diet challenge.

DIETARY FACTORS AFFECTING THE LEVEL OF PLASMA CHOLESTEROL IN HUMANS: THE ROLE OF FAT

1956 ◽  
Vol 34 (3) ◽  
pp. 441-455 ◽  
Author(s):  
J. M. R. Beveridge ◽  
W. F. Connell ◽  
G. A. Mayer
Keyword(s):  
Corn Oil ◽  
Plasma Cholesterol ◽  
Initial Period ◽  
Dietary Factors ◽  
Chicken Fat ◽  
Animal Fats ◽  
Percentage Decrease ◽  
Cholesterol Levels ◽  
The Individual ◽  
Average Individual

Three dietary experiments have been performed in which 36, 37, and 49 male medical students and staff members participated as experimental subjects. In each study, everyone consumed the same homogeneous formula diet for eight days at which time they were divided into five groups. One group was maintained on the original diet for a further eight days and the others were given diets varying in respect of the level and nature of the fat moiety. Protein supplied 16.9% of total calories in all experimental rations. In the first experiment, 37 subjects ingested a diet providing 58.5% of calories as corn oil. During the initial period the average of the individual percentage decreases in plasma cholesterol was 32.0 (P = < 0.01). Those continuing on corn oil displayed a further insignificant decrease. The others, receiving diets high in beef dripping, chicken fat, lard, and butter showed average individual percentage increases of 11.7 (P = > 0.05), 12.7 (P = > 0.05), 15.4 (P = < 0.01), and 28.8 (P = < 0.01), respectively. In the second experiment, 49 subjects consumed a fat-free diet for eight days. The average individual percentage decrease in plasma cholesterol was 22.2 (P = < 0.01). Those continuing on the fat-free diet showed little further change. Those ingesting 20 and 60% of calories as corn oil showed further percentage decreases of 6.9 (P = > 0.05) and 15.2 (P = < 0.01), respectively. By contrast, those receiving diets providing 20 and 60%, of calories as butterfat showed respectively percentage increases of 6.6 (P = > 0.05) and 21.7 (P = < 0.01). In the third experiment, 36 subjects ingested for eight days a diet in which butterfat provided 60% of calories. The plasma cholesterol level remained essentially constant, and did not change significantly in those continuing on this diet for a further eight days. The composition of the fat moiety in the remaining groups in terms of per cent calories derived from butter-fat and corn oil respectively was: 45: 15; 30: 30; 15: 45; and 0: 60. The averages of the individual percentage decreases in plasma cholesterol values were, respectively, 3.9, 15.9, 27.1, and 32.0. Except for the lowest of these values all the changes are highly significant (P = < 0.01). In addition to other conclusions that may be drawn from this work, these studies reveal that (1) there is a factor (or are factors) in certain animal fats that acts to elevate plasma cholesterol levels, and (2) there is a factor (or are factors) in corn oil that acts to depress plasma cholesterol levels.

THE EFFECT OF THE TYPE AND AMOUNT OF DIETARY FAT ON THE LEVEL OF PLASMA TRIGLYCERIDES IN HUMAN SUBJECTS IN THE POSTABSORPTIVE STATE

1964 ◽  
Vol 42 (7) ◽  
pp. 999-1003 ◽  
Author(s):  
J. M. R. Beveridge ◽  
S. N. Jagannathan ◽  
W. Ford Connell
Keyword(s):  
Dietary Fat ◽  
Free Choice ◽  
Corn Oil ◽  
Plasma Cholesterol ◽  
Human Subjects ◽  
Fasting State ◽  
Carbohydrate Diet ◽  
Plasma Triglycerides ◽  
Formula Diets ◽  
Male Subjects

Fifty-eight healthy university students consumed homogenized formula diets for 16 days, and plasma triglycerides were determined on samples of blood obtained from the subjects in the fasting state at days 0, 4, 8, 12, and 16. On a fat-free (high-carbohydrate) diet there was a sex difference in the response, with a group of 11 males showing a highly significant increase (over twofold) and a group of 14 females showing no significant change. No change was observed in 10 male subjects transferred from their free-choice diet to a formula diet providing 45% of calories from butterfat. However, in the case of a group of 23 men who consumed a diet similarly high in corn oil, a significant decrease occurred and the values observed were also significantly lower than those obtained on the butterfat ration. The usual responses of the plasma cholesterol to these diets were observed. Although a parallelism was observed between the behavior of the plasma triglycerides and plasma cholesterol on diets containing fat, there was a divergence on the fat-free diet, characterized by an increase in plasma triglycerides in the males and no change in the females, whereas the usual decrease in plasma cholesterol occurred in both sexes.

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