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Ovarian senescence increases liver fibrosis in humans and zebrafish with steatosis.

Turola E, Petta S, Vanni E, Milosa F, Valenti L, Critelli R, Miele L, Maccio L, Calvaruso V, Fracanzani AL, Bianchini M, Raos N, Bugianesi E, Mercorella S, Di Giovanni M, Craxì A, Fargion S, Grieco A, Cammà C, Cotelli F, Villa E - Dis Model Mech (2015)

Bottom Line: In the entire cohort, at multivariate logistic regression, male gender [odds ratio (OR): 1.408, 95% confidence interval (95% CI): 0.779-2.542, P=0.25] vs women at reproductive age was not associated with F2-F4 fibrosis, whereas a trend was observed for menopause (OR: 1.752, 95% CI: 0.956-3.208, P=0.06).In women, menopause (OR: 2.717, 95% CI: 1.020-7.237, P=0.04) was independently associated with F2-F4 fibrosis.Similarly, in overfed zebrafish, old female fish with failing ovarian function [as demonstrated by extremely low circulating estradiol levels (1.4±0.1 pg/µl) and prevailing presence of atretic follicles in the ovaries] developed massive steatosis and substantial fibrosis (comparable with that occurring in males), whereas young female fish developed less steatosis and were totally protected from the development of fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Gastroenterology Unit, Department of Internal Medicine, University of Modena and Reggio Emilia, 41124 Modena, Italy.

No MeSH data available.


Related in: MedlinePlus

Assessment of hepatic fibrosis in overfed zebrafish. (A) Sirius Red staining of liver sections from young males, old males, young females and old female zebrafish at baseline, and after 24 weeks of overfeeding. Scale bar: 30 µm. (B) Quantification of liver fibrosis by using computer-assisted digital image analysis. Data are reported as collagen proportionate area (CPA) converted into a percentage. Three sections from five fish per subgroup were analyzed. Values are expressed as means±s.d. *P<0.0001 for young females versus all the other groups.
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DMM019950F3: Assessment of hepatic fibrosis in overfed zebrafish. (A) Sirius Red staining of liver sections from young males, old males, young females and old female zebrafish at baseline, and after 24 weeks of overfeeding. Scale bar: 30 µm. (B) Quantification of liver fibrosis by using computer-assisted digital image analysis. Data are reported as collagen proportionate area (CPA) converted into a percentage. Three sections from five fish per subgroup were analyzed. Values are expressed as means±s.d. *P<0.0001 for young females versus all the other groups.

Mentions: Liver fibrosis was assessed by using Sirius Red staining, which detects collagen (Fig. 3A). A significant increase in the level of fibrosis compared to that at baseline could be observed already at week 6 in young males (P<0.0001) and in old females (P=0.038). Fibrosis further increased at week 16 (young males: P<0.0001; old males: P=0.0003; old females: P=0.011 all vs their baseline) and at week 24 (young males: P<0.0001; old males: P<0.0001; old females: P=0.004 all vs their respective baseline). At all time points analyzed, young females did not show any increase in fibrosis as compared with their basal level (Fig. 3B). At week 24, young females had a significantly lower level of fibrosis as compared with that of all other groups (P<0.001 vs young males, old males and old females).Fig. 3.


Ovarian senescence increases liver fibrosis in humans and zebrafish with steatosis.

Turola E, Petta S, Vanni E, Milosa F, Valenti L, Critelli R, Miele L, Maccio L, Calvaruso V, Fracanzani AL, Bianchini M, Raos N, Bugianesi E, Mercorella S, Di Giovanni M, Craxì A, Fargion S, Grieco A, Cammà C, Cotelli F, Villa E - Dis Model Mech (2015)

Assessment of hepatic fibrosis in overfed zebrafish. (A) Sirius Red staining of liver sections from young males, old males, young females and old female zebrafish at baseline, and after 24 weeks of overfeeding. Scale bar: 30 µm. (B) Quantification of liver fibrosis by using computer-assisted digital image analysis. Data are reported as collagen proportionate area (CPA) converted into a percentage. Three sections from five fish per subgroup were analyzed. Values are expressed as means±s.d. *P<0.0001 for young females versus all the other groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4582103&req=5

DMM019950F3: Assessment of hepatic fibrosis in overfed zebrafish. (A) Sirius Red staining of liver sections from young males, old males, young females and old female zebrafish at baseline, and after 24 weeks of overfeeding. Scale bar: 30 µm. (B) Quantification of liver fibrosis by using computer-assisted digital image analysis. Data are reported as collagen proportionate area (CPA) converted into a percentage. Three sections from five fish per subgroup were analyzed. Values are expressed as means±s.d. *P<0.0001 for young females versus all the other groups.
Mentions: Liver fibrosis was assessed by using Sirius Red staining, which detects collagen (Fig. 3A). A significant increase in the level of fibrosis compared to that at baseline could be observed already at week 6 in young males (P<0.0001) and in old females (P=0.038). Fibrosis further increased at week 16 (young males: P<0.0001; old males: P=0.0003; old females: P=0.011 all vs their baseline) and at week 24 (young males: P<0.0001; old males: P<0.0001; old females: P=0.004 all vs their respective baseline). At all time points analyzed, young females did not show any increase in fibrosis as compared with their basal level (Fig. 3B). At week 24, young females had a significantly lower level of fibrosis as compared with that of all other groups (P<0.001 vs young males, old males and old females).Fig. 3.

Bottom Line: In the entire cohort, at multivariate logistic regression, male gender [odds ratio (OR): 1.408, 95% confidence interval (95% CI): 0.779-2.542, P=0.25] vs women at reproductive age was not associated with F2-F4 fibrosis, whereas a trend was observed for menopause (OR: 1.752, 95% CI: 0.956-3.208, P=0.06).In women, menopause (OR: 2.717, 95% CI: 1.020-7.237, P=0.04) was independently associated with F2-F4 fibrosis.Similarly, in overfed zebrafish, old female fish with failing ovarian function [as demonstrated by extremely low circulating estradiol levels (1.4±0.1 pg/µl) and prevailing presence of atretic follicles in the ovaries] developed massive steatosis and substantial fibrosis (comparable with that occurring in males), whereas young female fish developed less steatosis and were totally protected from the development of fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Gastroenterology Unit, Department of Internal Medicine, University of Modena and Reggio Emilia, 41124 Modena, Italy.

No MeSH data available.


Related in: MedlinePlus