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. 2022 Jul;179(13):3363-3381.
doi: 10.1111/bph.15804. Epub 2022 Feb 21.

Melatonin epigenetic potential on testicular functions and fertility profile in varicocele rat model is mediated by silent information regulator 1

Rehab E Abo El Gheit  1   2 , Nema A Soliman  3 , Salah A Nagla  4 , Rehab M El-Sayed  5 , Ghada A Badawi  5 , Marwa N Emam  1 , Muhammad Tarek Abdel Ghafar  6 , Marwa A A Ibrahim  7 , Noha R M Elswaidy  7 , Doaa A Radwan  8 , Hanan A Alshenawy  9 , Howayda E Khaled  10 , Samar Kamel  11 , Mervat H El-Saka  1 , Nermin M Madi  1 , Reham L Younis  1
Affiliations
Free article

Melatonin epigenetic potential on testicular functions and fertility profile in varicocele rat model is mediated by silent information regulator 1

Rehab E Abo El Gheit et al. Br J Pharmacol. 2022 Jul.
Free article

Erratum in

Abstract

Background and purpose: Varicocele is a leading cause of male infertility. Melatonin is a highly pleiotropic neurohormone. We aimed to characterize the melatonin epigenetic potential in varicocele and the involved molecular mechanisms.

Experimental approach: Fifty-two male albino rats were randomly divided into four groups (13 rats each): control (I), melatonin (II), varicocele (III) and melatonin treated varicocele (IV) groups. Left varicocele was induced by partial left renal vein ligation. Reproductive hormones, epididymal sperm functional parameters, testicular 3/17 β-hydroxysteroid dehydrogenases, antioxidant enzymes, malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase, 8-hydroxy-2'-deoxyguanosine and histopathological/Johnsen's score were evaluated. Flow cytometry and Comet were carried out to explore extent of sperm and testicular DNA damage. Testicular expression of silent information regulator 1 (SIRT1), forkhead transcription factors-class O (type1) (FOXO1), tumour suppressor gene, P53, cation channels of sperm (CatSper) and steroidogenic acute regulatory protein was evaluated by western blot technique. Testicular expression of Bcl-2 and its associated X protein and nuclear factor kappa-light-chain-enhancer of activated B cells were assayed by immunohistochemical staining. Testicular miR-34a expression was quantified by quantitative reverse transcription-polymerase chain reaction.

Key results: The varicocele induced testicular histological injury, enhanced oxidative stress, P53-mediated apoptosis, DNA damage and increased testicular miR-34a expression paralleled with down-regulated SIRT1/FOXO axis. Melatonin treatment of varicocele rats displayed antioxidant/anti-apoptotic efficacy and improved reproductive hormones axis, CatSper expression and fertility parameters. MiR-34a/SIRT1/FOXO1 epigenetic axis integrates testicular melatonin mediated intracellular transduction cascades in varicocele.

Conclusion and implications: Melatonin can be used as an adjuvant therapy to improve varicocele and its complication.

Keywords: CatSper; FOXO; MiR-34a; melatonin; silent information regulator 1; varicocele.

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References

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