Hypoxia presentation

Hypoxia affects sex differentiation and development, leading to a male dominated population in fish : 

Hypoxia affects sex differentiation and development, leading to a male dominated population in fish Rudolf Wu Centre for Coastal Pollution andamp; Conservation City University of Hong Kong

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Diaz andamp; Rosenberg, 1995 What is 'Hypoxia'? Shortage of oxygen andlt; 2 ml /L andlt;2.8 mg/L

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Hypoxia is A Pressing Global Problem

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andlt;2.8 mgO2/L Diaz andamp; Rosenberg 1995 Hypoxic areaandgt; 1 million Km2

150 “Dead Zones” all over the world: 

150 'Dead Zones' all over the world UNEP, 2004

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Hypoxia: Some Trend: 

Hypoxia: Some Trend Decrease in DO in many coastal areas in USA, China, Norway, UK, Sweden, Germany, Denmark, the Black Sea, Adriatic Seas in the last 30-80 years Diaz andamp; Rosenberg, 1995; Rabalais, 2001

Current situation: 

Current situation Increases in nutrient concentration, algal blooms, large scale hypoxia, and change of species composition, mass mortality of fish and decline in fisheries production are found in large coastal areas all over the world Diaz andamp; Rosenberg, 1995; Gray andamp; Wu, 2002

Experimental set up: 

5.8 mg/L 0.8 mg/L Experimental set up Eggs of zebrafish exposed to 0.8 and 5.8 mg O2/L for 3 months Studied growth, gonad wt. gametogenesis, malformation, sex hormones, sex ratio and various genes controlling synthesis of sex hormone and apoptosis over time Oxygen controller

Endocrine disruption occurs as early as 48hpf: 

Endocrine disruption occurs as early as 48hpf Shang andamp; Wu, 2004 ** pandlt;0.01

Endocrine disruption occurs as early as 48hpf: 

Endocrine disruption occurs as early as 48hpf Shang andamp; Wu, 2004 *** pandlt;0.005

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Under hypoxia, apoptosis concentrates in the head but not the tail Control Hypoxia

Hypoxia alters normal pattern of apoptosis: 

Hypoxia alters normal pattern of apoptosis

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Hypoxia tips sex balance & favors a male biased population : 

Hypoxia tips sex balance andamp; favors a male biased population Shang, Yu andamp; Wu, 2006 *** *** p andlt; 0.001

Where the girl are? : 

Where the girl are?

Expression of selected genesunder hypoxia: 

Expression of selected genes under hypoxia

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Sex differentiation/ reversal is completed Final maturation of the gonads Gonads differentiate into ovaries Spawning Sex differentiation begins Male 3-HSD (-) CYP11A (-) CYP19A (+) CYP19B (+) T/E2 (NC) Male 3-HSD (-) CYP11A (-) CYP19A (-) CYP19B (NC) T/E2 (NC) Female 3-HSD (+) CYP11A (-) CYP19A (+) CYP19B (+) T/E2 (+) Aromatase (-) Female 3-HSD (-) CYP11A (-) CYP19A (+) CYP19B (NC) T/E2 (+) Aromatase (-) (C) 60 dpf (D) 120 dpf (B) 40 dpf (A) 10 dpf 10-12 dpf 23-25 dpf 42 dpf 60 dpf 120 dpf Juvenile Adult Larval 3 dpf 90 dpf 30 dpf

In vitro evidence : 

In vitro evidence In vitro studies using H295R cell line

Overall Conclusions: 

Overall Conclusions Hypoxia affects very large areas and has caused major changes in aquatic ecosystems, as well as decline in fisheries production all over the world For the first time, we found that hypoxia is an endocrine disruptor, and impairs reproduction of fish

Overall Conclusions: 

Overall Conclusions For the first time in science, we found that : Hypoxia alters various genes controlling synthesis of sex hormones Alternation of sex hormones affects sex differentiation and sex development, and favors a male-biased population in fish A higher male to female ratio will greatly reduce the chance of fish reproduction

Overall Conclusions: 

Overall Conclusions Since the genes and hormones controlling sex differentiation and reproduction are highly conserved, the endocrine disrupting effects and biased sex ratio observed in fish may also occur in other vertebrates. These are likely to be the major factors leading to decline of natural populations in hypoxic waters The problem of hypoxia is likely to get worse in the coming years

Epilogue: 

Epilogue Sex ratio in human depends on level of sex hormones of father and mother during conception, and high hormone level during conception favors subsequent birth of sons (James, 2004) Patients suffering from sleeping apnea have lower sex drive and testosterone level (Saaresranta andamp; Polo, 2003)

Acknowledgments: 

Acknowledgments This research was supported by the Area of Excellence Grant (AoE/P-04/04) from the University Grants Council, HK SAR government Dr. Eva Shang

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