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Beyond IUI, IVF and ICSI - New developments in - eshre 2013

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Pharmacological impacts on sperm function<br />

Critical to appreciate mechanisms <strong>in</strong>volved <strong>in</strong> causation of defective sperm function - particularly role<br />

of superoxide anion <strong>and</strong> hydrogen peroxide<br />

DHE<br />

Superoxide anion generation<br />

Eth<br />

H 2N<br />

Peak 1<br />

314<br />

NH2<br />

2OH Eth<br />

H 2N<br />

Et +<br />

Peak 2<br />

2OHEt +<br />

330 OH<br />

NH2<br />

Superoxide specific<br />

Lipid peroxidation generates powerful electrophiles<br />

acrole<strong>in</strong><br />

O 4-oxo-2 (E)-nonenal<br />

O<br />

O<br />

MSR (%)<br />

100<br />

80<br />

60<br />

40<br />

20<br />

Fe 2+<br />

Malondialdehyde<br />

O O<br />

*<br />

***<br />

0<br />

Pos 0 100 200 400 800<br />

*<br />

4-Hydroxynonenal (µM)<br />

O<br />

170<br />

130<br />

100<br />

70<br />

55<br />

40<br />

35<br />

25<br />

α-Tubul<strong>in</strong><br />

4-hydroxynonenal<br />

4HNE drives mitochondrial ROS generation<br />

4-Hydroxynonenal (µM)<br />

50<br />

40<br />

30<br />

20<br />

10<br />

0<br />

0 10 20 30 40<br />

DHE Positive (%)<br />

R 2 = 0.85<br />

4-Hydroxynonenal (µM)<br />

15<br />

40<br />

30<br />

20<br />

10<br />

OH<br />

SDHA HNE<br />

0<br />

0 10 20 30 40 50 60<br />

MSR Positive (%)<br />

R 2 = 0.89<br />

SDHA/HNE<br />

Page 28 of 127

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