DELETERIOUS EFFECTS OF CHRONIC MODERATE ALCOHOL INTAKE BY FEMALE MICE ON PREIMPLANTATION EMBRYO GROWTH IN VITRO

Maternal obesity results in reproductive complications, whereas the impact of paternal obesity is unclear. In the present study, the effects of parental obesity on preimplantation embryo cell cycle length and carbohydrate utilisation were investigated. Maternal and paternal obesity were assessed independently by deriving zygotes from normal or obese C57BL/6 female mice mated with normal Swiss male mice (maternal obesity), or from normal Swiss female mice mated with normal or obese C57BL/6 male mice (paternal obesity). Zygotes were cultured in vitro and development was then assessed by time-lapse microscopy and metabolism determined using ultramicrofluorescence. Maternal obesity was associated with a significant delay in precompaction cell cycle kinetics from the 1-cell stage. A significant increase in glucose consumption by embryos from obese compared with normal females occurred after compaction, although glycolysis remained unchanged. Similarly, paternal obesity led to significant delays in cell cycle progression during preimplantation embryo development. However, this developmental delay was observed from the second cleavage stage onwards, following embryonic genome activation. Blastocysts from obese males showed disproportionate changes in carbohydrate metabolism, with significantly increased glycolysis. Overall, metabolic changes were not inhibitory to blastocyst formation; however, blastocyst cell numbers were significantly lower when either parent was obese. These data suggest that both maternal and paternal obesity significantly impacts preimplantation embryo physiology.

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Murine sperm capacitation, oocyte penetration and decondensation following moderate alcohol intake

Reproduction ◽

10.1530/rep-17-0507 ◽

2018 ◽

Vol 155 (6) ◽

pp. 529-541 ◽

Cited By ~ 3

Author(s):

Melisa C Sánchez ◽

Vanina A Fontana ◽

Camila Galotto ◽

Maite Y Cambiasso ◽

Cristian M A Sobarzo ◽

...

Keyword(s):

Alcohol Intake ◽

Sperm Morphology ◽

Free Water ◽

Sperm Head ◽

Chronic Alcohol ◽

Chronic Alcohol Abuse ◽

Acrosomal Exocytosis ◽

Outbred Mice ◽

Moderate Alcohol Intake

Male chronic alcohol abuse causes testicular failure and infertility. We analyzed the effects of moderate sub-chronic alcohol intake on sperm morphology, capacitation, fertilization and sperm head decondensation. CF-1 male mice were administered 15% ethanol in drinking water for 15 days; control mice received ethanol-free water. Similar patterns of tyrosine phosphorylation were observed in capacitated spermatozoa of control and treated males. Percentage of hyperactivation (H) and spontaneous (SAR) and progesterone-induced (IAR) acrosome reaction significantly decreased at 120 and 150 min of capacitation in treated males compared to controls (H: 14.1 ± 2.5 vs 23.7 ± 2.6, P < 0.05; SAR-T120 min: 17.9 ± 2.5 vs 32.9 ± 4.1, P < 0.01; IAR-150 min: 43.3 ± 3.5 vs 73.1 ± 1.1, P < 0.001, n = 6). During in vitro fertilization (2.5, 3.5 and 4.5 h post-insemination), there was an increased percentage of fertilized oocytes (with a decondensed sperm head and one or two pronuclei) in treated males (P < 0.001, n = 7). After 60 min of in vitro decondensation with glutathione plus heparin, the percentage of decondensed sperm heads was significantly higher in treated males than in controls (mean ± s.d.: 57.1 ± 5.6 vs 48.3 ± 4.5, P < 0.05, n = 5). The percentage of morphologically normal sperm heads was significantly decreased in treated males with respect to controls (P < 0.001, n = 9). These results show that short-term moderate alcohol consumption in outbred mice affect sperm morphology, hyperactivation, acrosomal exocytosis, and the dynamics of in vitro fertilization and in vitro sperm nuclear decondensation.

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Faculty Opinions recommendation of Moderate alcohol intake and cancer incidence in women.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1160079.628308 ◽

2009 ◽

Author(s):

Wendy Demark-Wahnefried

Keyword(s):

Cancer Incidence ◽

Alcohol Intake ◽

Moderate Alcohol Intake

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Evaluation of the In Vivo Acute Toxicity and In Vitro Hemolytic and Immunomodulatory Activities of the Moringa oleifera Flower Trypsin Inhibitor (MoFTI)

Protein and Peptide Letters ◽

10.2174/0929866527999201113105858 ◽

2020 ◽

Vol 27 ◽

Author(s):

Leydianne Leite de Siqueira Patriota ◽

Dayane Kelly Dias do Nascimento Santos ◽

Bárbara Rafaela da Silva Barros ◽

Lethícia Maria de Souza Aguiar ◽

Yasmym Araújo Silva ◽

...

Keyword(s):

Acute Toxicity ◽

Trypsin Inhibitor ◽

Hemolytic Activity ◽

Moringa Oleifera ◽

Biological Activities ◽

Hematological Parameters ◽

Behavioral Alterations ◽

Female Mice

Background: Protease inhibitors have been isolated from plants and present several biological activities, including immunomod-ulatory action. Objective: This work aimed to evaluate a Moringa oleifera flower trypsin inhibitor (MoFTI) for acute toxicity in mice, hemolytic activity on mice erythrocytes and immunomodulatory effects on mice splenocytes. Methods: The acute toxicity was evaluated using Swiss female mice that received a single dose of the vehicle control or MoFTI (300 mg/kg, i.p.). Behavioral alterations were observed 15–240 min after administration, and survival, weight gain, and water and food consumption were analyzed daily. Organ weights and hematological parameters were analyzed after 14 days. Hemolytic activity of MoFTI was tested using Swiss female mice erythrocytes. Splenocytes obtained from BALB/c mice were cultured in the absence or presence of MoFTI for the evaluation of cell viability and proliferation. Mitochondrial membrane potential (ΔΨm) and reactive oxygen species (ROS) levels were also determined. Furthermore, the culture supernatants were analyzed for the presence of cytokines and nitric oxide (NO). Results: MoFTI did not cause death or any adverse effects on the mice except for abdominal contortions at 15–30 min after administration. MoFTI did not exhibit a significant hemolytic effect. In addition, MoFTI did not induce apoptosis or necrosis in splenocytes and had no effect on cell proliferation. Increases in cytosolic and mitochondrial ROS release, as well as ΔΨm reduction, were observed in MoFTI-treated cells. MoFTI was observed to induce TNF-α, IFN-γ, IL-6, IL-10, and NO release. Conclusion: These results contribute to the ongoing evaluation of the antitumor potential of MoFTI and its effects on other immunological targets.

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Moderate alcohol intake promotes pancreatic ductal adenocarcinoma development in mice expressing oncogenic Kras

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00218.2019 ◽

2020 ◽

Vol 318 (2) ◽

pp. G265-G276

Author(s):

Kinji Asahina ◽

Steven Balog ◽

Edward Hwang ◽

Eugene Moon ◽

Emily Wan ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Pancreatic Ductal Adenocarcinoma ◽

Alcohol Drinking ◽

Calcium Binding ◽

Alcohol Intake ◽

Western Diet ◽

Mutant Mice ◽

Ductal Adenocarcinoma ◽

Moderate Alcohol Intake

Kras mutations are associated with pancreatic ductal adenocarcinoma (PDAC). Although tobacco smoking, pancreatitis, and obesity are known environmental risk factors for PDAC, the contribution of moderate alcohol intake to PDAC remains elusive. In the present study, we tested whether a combination of risk factors or moderate alcohol intake induces PDAC development in mice. Control Pdx1Cre and Pdx1Cre;LSL- KrasG12D mutant mice were fed a Western alcohol diet containing high levels of cholesterol and saturated fat, 3.5% alcohol, and lipopolysaccharide for 5 mo. In addition, mice were treated with cerulein, for induction of pancreatitis, and nicotine every month. Treatment with all of these risk factors promoted development of advanced pancreatic neoplasia and PDAC in the Pdx1Cre;LSL- KrasG12D mice but not in the control Pdx1Cre mice. Moderate alcohol intake or Western diet feeding also significantly promoted advanced neoplasia and PDAC development in Pdx1Cre;LSL- KrasG12D mice compared with mice fed a regular chow. Alcohol, but not Western diet, increased tumor development in the liver in the Pdx1Cre;LSL- KrasG12D mice, but its origin remained elusive due to leakiness of Pdx1Cre in hepatocytes. RNA-seq analysis revealed that alcohol feeding increases expression of markers for tumors ( Epcam, Krt19, Prom1, Wt1, and Wwtr1), stroma ( Dcn, Fn1, and Tnc), and cytokines ( Tgfb1 and Tnf) and decreases expression of Fgf21 and Il6 in the pancreatic tumor tissues. Immunostaining showed heterogeneous expression of nephronectin, S100 calcium-binding protein A6, and vascular cell adhesion molecule 1 in pancreatic tumors surrounded by podoplanin-positive stromal cells. Our data indicate that moderate alcohol drinking is a risk factor for development of PDAC. NEW & NOTEWORTHY Heavy alcohol intake has been suspected to be a risk factor of pancreatic ductal adenocarcinoma (PDAC) in humans. However, the contribution of moderate alcohol intake to PDAC development remains elusive. In the present study, we experimentally show that moderate alcohol feeding significantly induces advanced stages of pancreatic intraepithelial neoplasia development and invasive PDAC in Pdx1Cre;LSL- KrasG12D mutant mice. Our data indicate that moderate alcohol drinking is a risk factor for PDAC.

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Preimplantation embryo development in vitro: cooperative interactions among embryos and role of growth factors.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.87.12.4756 ◽

1990 ◽

Vol 87 (12) ◽

pp. 4756-4760 ◽

Cited By ~ 382

Author(s):

B. C. Paria ◽

S. K. Dey

Keyword(s):

Growth Factors ◽

Embryo Development ◽

Preimplantation Embryo ◽

Preimplantation Embryo Development ◽

Cooperative Interactions ◽

Development In Vitro

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Moderate alcohol intake increases fibrosis progression in untreated patients with hepatitis C virus infection

Journal of Viral Hepatitis ◽

10.1046/j.1365-2893.2002.00356.x ◽

2002 ◽

Vol 9 (3) ◽

pp. 235-241 ◽

Cited By ~ 98

Author(s):

J. Westin ◽

L. M. Lagging ◽

F. Spak ◽

N. Aires ◽

E. Svensson ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Infection ◽

Alcohol Intake ◽

Hepatitis C Virus Infection ◽

Fibrosis Progression ◽

Moderate Alcohol Intake

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Dietary Fucose Affects Macrophage Polarization and Reproductive Performance in Mice

Nutrients ◽

10.3390/nu13030855 ◽

2021 ◽

Vol 13 (3) ◽

pp. 855

Author(s):

Ekaterina A. Litvinova ◽

Victoria D. Bets ◽

Natalya A. Feofanova ◽

Olga V. Gvozdeva ◽

Kseniya M. Achasova ◽

...

Keyword(s):

Oxidative Phosphorylation ◽

Reproductive Performance ◽

Immune Status ◽

Macrophage Polarization ◽

Bacterial Species ◽

Peritoneal Macrophages ◽

M2 Macrophage ◽

Female Mice ◽

Intestinal Mucus

Intestinal mucus protects epithelial and immune cells from the gut resident microorganisms, and provides growth-promoting factors as mucus-derived O-glycans for beneficial bacteria. A lack of intestinal protective mucus results in changes in the commensal microflora composition, mucosal immune system reprogramming, and inflammation. Previous work has shown that fucose, the terminal glycan chain component of the intestinal glycoprotein Mucin2, and fucoidan polysaccharides have an anti-inflammatory effect in some mouse models of colitis. This study evaluates the effect of fucose on reproductive performance in heterozygous mutant Muc2 female mice. We found that even though Muc2+/− females are physiologically indistinguishable from C57Bl/6 mice, they have a significantly reduced reproductive performance upon dietary fucose supplementation. Metagenomic analysis reveals that the otherwise healthy wild-type siblings of Muc2−/− animals have reduced numbers of some of the intestinal commensal bacterial species, compared to C57BL/6 mice. We propose that the changes in beneficial microflora affect the immune status in Muc2+/− mice, which causes implantation impairment. In accordance with this hypothesis, we find that macrophage polarization during pregnancy is impaired in Muc2+/− females upon addition of fucose. Metabolic profiling of peritoneal macrophages from Muc2+/− females reveals their predisposition towards anaerobic glycolysis in favor of oxidative phosphorylation, compared to C57BL/6-derived cells. In vitro experiments on phagocytosis activity and mitochondrial respiration suggest that fucose affects oxidative phosphorylation in a genotype-specific manner, which might interfere with implantation depending on the initial status of macrophages. This hypothesis is further confirmed in BALB/c female mice, where fucose caused pregnancy loss and opposed implantation-associated M2 macrophage polarization. Taken together, these data suggest that intestinal microflora affects host immunity and pregnancy outcome. At the same time, dietary fucose might act as a differential regulator of macrophage polarization during implantation, depending on the immune status of the host.

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