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Hum. Reprod. Advance Access published online on February 11, 2008
Human Reproduction, doi:10.1093/humrep/dem425
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Sperm-mediated ‘reverse’ gene transfer: a role of reverse transcriptase in the generation of new genetic information

Corrado Spadafora

Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy

Tel: +39-06-49903117; Fax: +39-06-49903672; E-mail: cspadaf{at}tin.it

Sperm-mediated gene transfer (SMGT) is a procedure through which new genetic traits are introduced in animals by exploiting the ability of spermatozoa to take up exogenous DNA molecules and deliver them to oocytes at fertilization. The interaction of exogenous DNA with sperm cells is a regulated process mediated by specific factors; among those, a reverse transcriptase (RT) activity plays a central role in SMGT. ‘Retro-genes’ are generated either through reverse transcription of exogenous RNA internalized in spermatozoa, or through sequential transcription, splicing and reverse transcription of exogenous DNA. The resulting retro-genes are delivered to oocytes and transmitted to embryos and born animals as low-copy, transcriptionally competent, extrachromosomal structures capable of determining new phenotypic traits. Retro-genes can be further transmitted through sexual reproduction from founders to their F1 progeny: new genetic and phenotypic features, unlinked to chromosomes, can thus be generated and inherited in a non-Mendelian ratio. We have called this phenomenon sperm-mediated ‘reverse’ gene transfer (SMRGT). Thus, a RT-mediated machinery operates in sperm cells and is responsible for the genesis and non-Mendelian propagation of new genetic information. The features of RT-generated traits elicited in SMRGT resemble those characterized in recent studies of RNA-mediated inheritance of extra-genomic information.

Key words: sperm-mediated gene transfer/reverse transcriptase/transgenesis/extrachromosomal inheritance

Submitted on October 17, 2007; resubmitted on November 21, 2007; accepted on December 13, 2007.


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