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We thank Dr. Taha for his editorial on our article.1, 2 As discussed by Dr. Taha in a recent article for the British Society of Gastroenterology, the risk of NSAID-induced gastrointestinal damage should be addressed during long-term NSAID treatment, and we compliment Dr. Taha for emphasising the potential of a safe dietary supplement such as the probiotic strain Bifidobacterium breve Bif195 (DSM 33360), for aspirin users.3 We agree that alternative treatment strategies that may enable safe continuous NSAID treatment are warranted.

Background Gastric and duodenal ulcerations are common during multiple-dosing aspirin treatment, such as for prevention of cardiovascular disease. On capsule endoscopy, oral administration of the bacterial strain Bifidobacterium breve Bif195 (DSM 33360) reduced the risk of aspirin-induced small intestinal damage, without affecting cyclo-oxygenase-2 (COX-2) inhibition. Aim To evaluate endoscopically the effect of Bif195 on aspirin-induced stomach and duodenal mucosal damage Methods Twenty-five healthy volunteers underwent two intervention periods in a randomised, double-blind, placebo-controlled crossover design including four gastroduodenoscopies and 6 weeks washout. Each intervention was a 4-week oral co-treatment of aspirin 300 mg daily and Bif195 (≥1011 colony-forming units daily) or placebo. Primary endpoint was change in Lanza score - ranging from 0 (normal mucosa) to 4 (>10 erosions or ulcer). Results All 25 participants (56% females); age 27.3 (±4.8) years; BMI 23.2 (±3.4) kg/m2, completed the trial exhibiting significant increases in Lanza scores during placebo treatment as compared to baseline. Bif195 reduced gastric Lanza score with an odds ratio of 7.2 (95% confidence interval 1.72–30.08, p = 0.009) compared to placebo with no related adverse events. There were no significant changes in Lanza scores in the duodenum. Conclusions Bif195 reduces aspirin-induced gastric mucosal damage and may serve as a safe supplement during multiple-dosing aspirin treatment., Background: Gastric and duodenal ulcerations are common during multiple-dosing aspirin treatment, such as for prevention of cardiovascular disease. On capsule endoscopy, oral administration of the bacterial strain Bifidobacterium breve Bif195 (DSM 33360) reduced the risk of aspirin-induced small intestinal damage, without affecting cyclo-oxygenase-2 (COX-2) inhibition. Aim: To evaluate endoscopically the effect of Bif195 on aspirin-induced stomach and duodenal mucosal damage. Methods: Twenty-five healthy volunteers underwent two intervention periods in a randomised, double-blind, placebo-controlled crossover design including four gastroduodenoscopies and 6 weeks washout. Each intervention was a 4-week oral co-treatment of aspirin 300 mg daily and Bif195 (≥1011 colony-forming units daily) or placebo. Primary endpoint was change in Lanza score - ranging from 0 (normal mucosa) to 4 (>10 erosions or ulcer). Results: All 25 participants (56% females); age 27.3 (±4.8) years; BMI 23.2 (±3.4) kg/m2, completed the trial exhibiting significant increases in Lanza scores during placebo treatment as compared to baseline. Bif195 reduced gastric Lanza score with an odds ratio of 7.2 (95% confidence interval 1.72–30.08, p = 0.009) compared to placebo with no related adverse events. There were no significant changes in Lanza scores in the duodenum. Conclusions: Bif195 reduces aspirin-induced gastric mucosal damage and may serve as a safe supplement during multiple-dosing aspirin treatment.

We thank Dr. Taha for his editorial on our article.1, 2 As discussed by Dr. Taha in a recent article for the British Society of Gastroenterology, the risk of NSAID-induced gastrointestinal damage should be addressed during long-term NSAID treatment, and we compliment Dr. Taha for emphasising the potential of a safe dietary supplement such as the probiotic strain Bifidobacterium breve Bif195 (DSM 33360), for aspirin users.3 We agree that alternative treatment strategies that may enable safe continuous NSAID treatment are warranted.

Background Gastric and duodenal ulcerations are common during multiple-dosing aspirin treatment, such as for prevention of cardiovascular disease. On capsule endoscopy, oral administration of the bacterial strain Bifidobacterium breve Bif195 (DSM 33360) reduced the risk of aspirin-induced small intestinal damage, without affecting cyclo-oxygenase-2 (COX-2) inhibition. Aim To evaluate endoscopically the effect of Bif195 on aspirin-induced stomach and duodenal mucosal damage Methods Twenty-five healthy volunteers underwent two intervention periods in a randomised, double-blind, placebo-controlled crossover design including four gastroduodenoscopies and 6 weeks washout. Each intervention was a 4-week oral co-treatment of aspirin 300 mg daily and Bif195 (≥1011 colony-forming units daily) or placebo. Primary endpoint was change in Lanza score - ranging from 0 (normal mucosa) to 4 (>10 erosions or ulcer). Results All 25 participants (56% females); age 27.3 (±4.8) years; BMI 23.2 (±3.4) kg/m2, completed the trial exhibiting significant increases in Lanza scores during placebo treatment as compared to baseline. Bif195 reduced gastric Lanza score with an odds ratio of 7.2 (95% confidence interval 1.72–30.08, p = 0.009) compared to placebo with no related adverse events. There were no significant changes in Lanza scores in the duodenum. Conclusions Bif195 reduces aspirin-induced gastric mucosal damage and may serve as a safe supplement during multiple-dosing aspirin treatment., Background: Gastric and duodenal ulcerations are common during multiple-dosing aspirin treatment, such as for prevention of cardiovascular disease. On capsule endoscopy, oral administration of the bacterial strain Bifidobacterium breve Bif195 (DSM 33360) reduced the risk of aspirin-induced small intestinal damage, without affecting cyclo-oxygenase-2 (COX-2) inhibition. Aim: To evaluate endoscopically the effect of Bif195 on aspirin-induced stomach and duodenal mucosal damage. Methods: Twenty-five healthy volunteers underwent two intervention periods in a randomised, double-blind, placebo-controlled crossover design including four gastroduodenoscopies and 6 weeks washout. Each intervention was a 4-week oral co-treatment of aspirin 300 mg daily and Bif195 (≥1011 colony-forming units daily) or placebo. Primary endpoint was change in Lanza score - ranging from 0 (normal mucosa) to 4 (>10 erosions or ulcer). Results: All 25 participants (56% females); age 27.3 (±4.8) years; BMI 23.2 (±3.4) kg/m2, completed the trial exhibiting significant increases in Lanza scores during placebo treatment as compared to baseline. Bif195 reduced gastric Lanza score with an odds ratio of 7.2 (95% confidence interval 1.72–30.08, p = 0.009) compared to placebo with no related adverse events. There were no significant changes in Lanza scores in the duodenum. Conclusions: Bif195 reduces aspirin-induced gastric mucosal damage and may serve as a safe supplement during multiple-dosing aspirin treatment.

Candida species overgrowth in the human gut is considered a prerequisite for invasive candidiasis, but our understanding of gut bacteria promoting or restricting this overgrowth is still limited. By integrating cross-sectional mycobiome and shotgun metagenomics data from the stool of 75 male and female cancer patients at risk but without systemic candidiasis, bacterial communities in high Candida samples display higher metabolic flexibility yet lower contributional diversity than those in low Candida samples. We develop machine learning models that use only bacterial taxa or functional relative abundances to predict the levels of Candida genus and species in an external validation cohort with an AUC of 78.6–81.1%. We propose a mechanism for intestinal Candida overgrowth based on an increase in lactate-producing bacteria, which coincides with a decrease in bacteria that regulate short chain fatty acid and oxygen levels. Under these conditions, the ability of Candida to harness lactate as a nutrient source may enable Candida to outcompete other fungi in the gut.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that poses health challenges worldwide and is expected to continue to rise dramatically. NAFLD is associated with metabolic syndrome, type 2 diabetes mellitus, and impaired gut health. Increased gut permeability, caused by disturbance of tight junction proteins, allows passage of damaging microbial components that, upon reaching the liver, have been proposed to trigger the release of inflammatory cytokines and generate cellular stress. A growing body of research has suggested the utilization of targeted probiotic supplements as a preventive therapy to improve gut barrier function and tight junctions. Furthermore, specific microbial interactions and metabolites induce the secretion of hormones such as GLP-1, resulting in beneficial effects on liver health. To increase the likelihood of finding beneficial probiotic strains, we set up a novel screening platform consisting of multiple in vitro and ex vivo assays for the screening of 42 bacterial strains. Analysis of transepithelial electrical resistance response via co-incubation of the 42 bacterial strains with human colonic cells (Caco-2) revealed improved barrier integrity. Then, strain-individual metabolome profiling was performed revealing species-specific clusters. GLP-1 secretion assay with intestinal secretin tumor cell line (STC-1) found at least seven of the strains tested capable of enhancing GLP-1 secretion in vitro. Gene expression profiling in human biopsy-derived intestinal organoids was performed using next generation sequencing transcriptomics post bacterial co-incubation. Here, different degrees of immunomodulation by the increase in certain cytokine and chemokine transcripts were found. Treatment of mouse primary hepatocytes with selected highly produced bacterial metabolites revealed that indole metabolites robustly inhibited de novo lipogenesis. Collectively, through our comprehensive bacterial screening pipeline, no

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that poses health challenges worldwide and is expected to continue to rise dramatically. NAFLD is associated with metabolic syndrome, type 2 diabetes mellitus, and impaired gut health. Increased gut permeability, caused by disturbance of tight junction proteins, allows passage of damaging microbial components that, upon reaching the liver, have been proposed to trigger the release of inflammatory cytokines and generate cellular stress. A growing body of research has suggested the utilization of targeted probiotic supplements as a preventive therapy to improve gut barrier function and tight junctions. Furthermore, specific microbial interactions and metabolites induce the secretion of hormones such as GLP-1, resulting in beneficial effects on liver health. To increase the likelihood of finding beneficial probiotic strains, we set up a novel screening platform consisting of multiple in vitro and ex vivo assays for the screening of 42 bacterial strains. Analysis of transepithelial electrical resistance response via co-incubation of the 42 bacterial strains with human colonic cells (Caco-2) revealed improved barrier integrity. Then, strain-individual metabolome profiling was performed revealing species-specific clusters. GLP-1 secretion assay with intestinal secretin tumor cell line (STC-1) found at least seven of the strains tested capable of enhancing GLP-1 secretion in vitro. Gene expression profiling in human biopsy-derived intestinal organoids was performed using next generation sequencing transcriptomics post bacterial co-incubation. Here, different degrees of immunomodulation by the increase in certain cytokine and chemokine transcripts were found. Treatment of mouse primary hepatocytes with selected highly produced bacterial metabolites revealed that indole metabolites robustly inhibited de novo lipogenesis. Collectively, through our comprehensive bacterial screening pipeline, no

The microbiota has been shown to have the potential to affect appetite and blood lipids positively in animal studies. We investigated if four weeks supplementation with Lactobacillus paracasei subsp. paracasei L. casei W8® (L. casei W8) had an effect on subjective appetite sensation, ad libitum energy intake, glucagon-like peptide 1 (GLP- 1), glucose and insulin response in humans. Secondarily, we explored potential effects on blood lipids, fatty acids and stearoyl-CoA desaturase-1 (SCD1) activity in humans as well as SCD1 expression in piglets given L. casei W8 for two weeks. 64 healthy participants completed the double-blinded, randomised, controlled, parallel four weeks study with supplementation of L. casei W8 (1010 cfu) or placebo capsules. A meal test was conducted before and after the intervention, where subjective appetite, ad libitum energy intake, GLP-1, glucose and insulin response were measured. Additionally fasting blood lipids and fatty acids concentrations were measured. Sixteen piglets were randomised into two groups: L. casei W8 (1010 cfu/day) as top dressing on morning fed or no treatment. After two weeks piglets were sacrificed and tissue from ileum, jejunum and skeletal muscle were sampled for mRNA analyses of SCD1 expression. Compared to placebo, L. casei W8 did not affect appetite, ad libitum energy intake, GLP-1, glucose and insulin response and total, high-density or low-density lipoprotein cholesterol levels after four weeks intervention. Triacylglycerol decreased in the L. casei W8 group compared to placebo at week 4 (P=0.03). The C16:1n-7/C16:0 ratio, reflecting SCD1 activity, tended to decrease when having L. casei W8 (P=0.06) compared to placebo. Muscle SCD1 expression decreased in piglets supplemented with L. casei W8 compared to control. In conclusion, supplementation with L. casei W8 did not affect appetite parameters, glucose or insulin responses; but appear to be able to lower triacylglycerol levels, possibly by reducing its prod

Exposure to PCBs may be an etiologic factor for breast cancer. The cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes are involved in estrogen metabolism and PCB metabolism, both of which may relate to breast cancer susceptibility. Polymorphisms in genes regulating these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk. When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR = 0.41; 95% CI: 0.29-0.89). We found no statistically significant interactions between any of the PCB groups and CYP1B1 or COMT polymorphisms on the risk of breast cancer.

Background: Probiotic bacteria have been shown to have various effects on the microbiota; this may also affect appetite and may help promote weight loss and maintenance. Objective: This study was conducted to investigate the effect of Lactobacillus paracasei subsp paracasei L. casei W8 (L. casei W8) on glucagon-like peptide-1 (GLP-1) responses in an isolated pig intestine, in piglets and postprandially in humans. Additionally, the effect on subjective appetite, ad libitum energy intake, and glucose and insulin responses in humans was investigated. Design: Piglets were fed with probiotics for 2 weeks and the effect on glucagon encoding gene (GCG) was investigated. An isolated pig intestine was perfused with L. casei W8 and the GLP-1 response was measured. Twenty-one subjects completed a randomized, controlled, crossover study with three arms. Each participant completed 3 test days testing the effect of low dose (LD) (10(9) CFU), high dose (HD) (10(10) CFU) L. casei W8 or placebo capsule. Subjective appetite was assessed before an ad libitum lunch was served. GLP-1, insulin and glucose concentrations were analyzed. Results: Two weeks of treatment of piglets with L. casei W8 resulted in an increase in GCG expression compared to control animals (P <0.05). L. casei W8 increased the GLP-1 response in the isolated pig intestine. In humans, L. casei W8 had an overall effect on energy intake (P = 0.03), but no effects on subjective appetite sensation, overall glucose and insulin response and on GLP-1 release were observed (P > 0.1). Conclusion: The probiotic bacteria L. casei W8 appears to lower food intake acutely, but the underlying mechanisms are not understood.

Exposure to PCBs may be an etiologic factor for breast cancer. The cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes are involved in estrogen metabolism and PCB metabolism, both of which may relate to breast cancer susceptibility. Polymorphisms in genes regulating these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk. When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR = 0.41; 95% CI: 0.29-0.89). We found no statistically significant interactions between any of the PCB groups and CYP1B1 or COMT polymorphisms on the risk of breast cancer.

Background: Probiotic bacteria have been shown to have various effects on the microbiota; this may also affect appetite and may help promote weight loss and maintenance. Objective: This study was conducted to investigate the effect of Lactobacillus paracasei subsp paracasei L. casei W8 (L. casei W8) on glucagon-like peptide-1 (GLP-1) responses in an isolated pig intestine, in piglets and postprandially in humans. Additionally, the effect on subjective appetite, ad libitum energy intake, and glucose and insulin responses in humans was investigated. Design: Piglets were fed with probiotics for 2 weeks and the effect on glucagon encoding gene (GCG) was investigated. An isolated pig intestine was perfused with L. casei W8 and the GLP-1 response was measured. Twenty-one subjects completed a randomized, controlled, crossover study with three arms. Each participant completed 3 test days testing the effect of low dose (LD) (10(9) CFU), high dose (HD) (10(10) CFU) L. casei W8 or placebo capsule. Subjective appetite was assessed before an ad libitum lunch was served. GLP-1, insulin and glucose concentrations were analyzed. Results: Two weeks of treatment of piglets with L. casei W8 resulted in an increase in GCG expression compared to control animals (P <0.05). L. casei W8 increased the GLP-1 response in the isolated pig intestine. In humans, L. casei W8 had an overall effect on energy intake (P = 0.03), but no effects on subjective appetite sensation, overall glucose and insulin response and on GLP-1 release were observed (P > 0.1). Conclusion: The probiotic bacteria L. casei W8 appears to lower food intake acutely, but the underlying mechanisms are not understood.

Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16a-hydroxyestrone (16a-OHE1), and their ratio (2:16a-OHE1) in relation to breast cancer risk. ¿Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status.¿Results: Higher premenopausal 2:16a-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16a-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003). ¿Conclusions: Premenopausal urinary 2:16a-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16a-OHE1 overall, although obesity may modify associations with 2-OHE1.

Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16a-hydroxyestrone (16a-OHE1), and their ratio (2:16a-OHE1) in relation to breast cancer risk. ¿Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using enzyme linked immunosorbent assays. Study-specific and combined multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated based on tertiles of estrogen metabolites. Multinomial logistic regression models were fit according to hormone receptor status.¿Results: Higher premenopausal 2:16a-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16a-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvsI=0.93; 95% CI: 0.65-1.33); however, the association between 2-OHE1 and risk varied by body mass index (p-interaction=0.003). ¿Conclusions: Premenopausal urinary 2:16a-OHE1 may play a role in breast carcinogenesis; however, larger studies are needed. Our findings do not support reduced breast cancer risk with higher postmenopausal 2:16a-OHE1 overall, although obesity may modify associations with 2-OHE1.

Udgivelsesdato: 2009-Oct-1, In utero exposure to diesel exhaust particles may reduce sperm production in adulthood. We investigated the effect of prenatal exposure to diesel exhaust particles on the male reproductive system and assessed endocrine disruption and regulation of aquaporin expression as possible mechanisms of action. Dams inhaled 20 mg/m(3) of diesel exhaust particle standard reference material 2975 (SRM2975) or clean air for 1h/day on day 7-19 during pregnancy. Male offspring were killed on day 170 after birth. The dams that had inhaled SRM2975 delivered offspring, which in adulthood had reduced daily sperm production (P=0.046, Mann-Whitney U-test), whereas there were no differences in the body weight, testis weight and anogenital distance. There was no difference in plasma testosterone and estradiol concentrations, although some samples were not analyzed precisely because of technical problems. The gene regulation of the androgen receptor, anti-Müllerian hormone, estrogen receptor-alpha, estrogen receptor-beta, follicle-stimulating hormone receptor, insulin-like growth factor 3, luteinising hormone receptor, and aromatase in testes, were not significantly altered in the group exposed in utero to SRM2975 compared to controls. These data indicate that prenatal exposure to SRM2975 was not associated with endocrine disruptor activity in adulthood. There was no significant change in expression levels of aquaporins 7, 8 and 9 in testes tissue, measured as mRNA expression and protein levels by immunohistochemistry. In conclusion, prenatal exposure to SRM2975 was associated with reduced daily sperm production in adulthood, which was not possible to clearly associate with altered endocrine function or expression of aquaporins in the testes.

Udgivelsesdato: 2009-Oct-1, In utero exposure to diesel exhaust particles may reduce sperm production in adulthood. We investigated the effect of prenatal exposure to diesel exhaust particles on the male reproductive system and assessed endocrine disruption and regulation of aquaporin expression as possible mechanisms of action. Dams inhaled 20 mg/m(3) of diesel exhaust particle standard reference material 2975 (SRM2975) or clean air for 1h/day on day 7-19 during pregnancy. Male offspring were killed on day 170 after birth. The dams that had inhaled SRM2975 delivered offspring, which in adulthood had reduced daily sperm production (P=0.046, Mann-Whitney U-test), whereas there were no differences in the body weight, testis weight and anogenital distance. There was no difference in plasma testosterone and estradiol concentrations, although some samples were not analyzed precisely because of technical problems. The gene regulation of the androgen receptor, anti-Müllerian hormone, estrogen receptor-alpha, estrogen receptor-beta, follicle-stimulating hormone receptor, insulin-like growth factor 3, luteinising hormone receptor, and aromatase in testes, were not significantly altered in the group exposed in utero to SRM2975 compared to controls. These data indicate that prenatal exposure to SRM2975 was not associated with endocrine disruptor activity in adulthood. There was no significant change in expression levels of aquaporins 7, 8 and 9 in testes tissue, measured as mRNA expression and protein levels by immunohistochemistry. In conclusion, prenatal exposure to SRM2975 was associated with reduced daily sperm production in adulthood, which was not possible to clearly associate with altered endocrine function or expression of aquaporins in the testes.

Udgivelsesdato: 2008-May, Aquaporins (AQP) have important solute transport functions in many tissues including the epididymal efferent ducts (ED) and in the liver. We investigated the effect of neonatal exposure to diethylstilbestrol (DES) on AQP9 expressions in the ED and in the liver of rats. DES was administered from day 2 to day 20 postnatally at a dose of 4,8 microg/day, and AQP9 protein and mRNA were measured by immunoblotting and real-time PCR, respectively, along with immunohistochemistry. DES caused hepatic downregulation of AQP9 at both the protein and mRNA level; however, decreased AQP9 labeling was only observed in the periportal zone. In the ED, AQP9 protein expression was increased in the DES-treated animals by 300% that could be ascribed to a widening of the ED lumen, whereas no difference was observed in AQP9 mRNA expression. Immunohistochemical findings revealed that AQP9 expression was confined to the epithelial cells of the ED. In conclusion, neonatal DES exposure appears to upregulate AQP9 channels in the ED in male rats, whereas a downregulation in the hepatic expression was observed, particularly in the periacinous area.

Udgivelsesdato: 2008-May, Aquaporins (AQP) have important solute transport functions in many tissues including the epididymal efferent ducts (ED) and in the liver. We investigated the effect of neonatal exposure to diethylstilbestrol (DES) on AQP9 expressions in the ED and in the liver of rats. DES was administered from day 2 to day 20 postnatally at a dose of 4,8 microg/day, and AQP9 protein and mRNA were measured by immunoblotting and real-time PCR, respectively, along with immunohistochemistry. DES caused hepatic downregulation of AQP9 at both the protein and mRNA level; however, decreased AQP9 labeling was only observed in the periportal zone. In the ED, AQP9 protein expression was increased in the DES-treated animals by 300% that could be ascribed to a widening of the ED lumen, whereas no difference was observed in AQP9 mRNA expression. Immunohistochemical findings revealed that AQP9 expression was confined to the epithelial cells of the ED. In conclusion, neonatal DES exposure appears to upregulate AQP9 channels in the ED in male rats, whereas a downregulation in the hepatic expression was observed, particularly in the periacinous area.