Role of endogenous reverse transcriptase in murine early embryo development

Abstract

We report that a reverse transcriptase (RT) activity is present in early cleavage stage embryos as determined by a Polymerase chain reaction (PCR)-based detection assay. In an attempt to establish whether this activity plays a role in early embryonic development, we have blocked the endogenous RT by two independent approaches: (1) embryos were exposed to nevirapine, a highly specific nonnucleoside inhibitor of RT activity; (2) anti-RT antibody was microinjected into the nucleus of one blastomere of 2-cell embryos. When embryos were exposed to nevirapine in the developmental window between late 1-cell and 4-cell stages, development was arrested before the blastocyst stage. In contrast, development was not affected when embryos were exposed to nevirapine after the eight-cell stage. Developmental arrest was also induced when anti-RT antibody was microinjected in one blastomere of 2-cell embryos. Analysis of gene expression by RT-PCR in nevirapine-arrested 2-cell embryos revealed an extensive and specific reprogramming of gene expression, involving both developmentally regulated and constitutively expressed genes, compared to control embryos. These results support the conclusion that an endogenous RT activity is required in mouse early embryogenesis specifically between the late 1-cell and the 4-cell stage.

Activation of Human Long Interspersed Nuclear Element 1 Retrotransposition by Benzo(a)pyrene, an Ubiquitous Environmental Carcinogen

“…Endogenous reverse transcriptase is involved in proliferation and differentiation of tumorigenic and nondifferentiated cells (56) and is essential in murine early embryo development (57). Inhibition of reverse transcriptase causes developmental arrest during preimplantation, which is associated with reprogramming of gene expression (57).…”

“…Inhibition of reverse transcriptase causes developmental arrest during preimplantation, which is associated with reprogramming of gene expression (57). Moreover, down-regulation of L1 reverse transcriptase expression with small interfering RNA induces a differentiated morphology in transformed cells (58), and pharmacologic inhibition of reverse transcriptase reduces the growth of human tumor xenografts in athymic nude mice (58).…”

Factors regulating endogenous retroviral sequences in human and mouse

“…However, reverse transcriptase may be a critical factor in early mouse embryogenesis. Pittoggi et al (2003) have shown that the impairment of reverse transcriptase (using either the drug nevirapine or an antibody) between the late one-cell and the four-cell stage induces a developmental arrest before the blastocyst stage. In contrast, development was not affected when embryos were exposed to nevirapine after the eight-cell stage.…”

An alternative approach to medical genetics based on modern evolutionary biology. Part 2: retroviral symbiosis

“…31 They further demonstrated that reverse transcriptase inhibition caused a substantial reprogramming of gene expression in arrested embryos, involving both developmental and translational genes. 32 This suggests that endogenous retroviruses, or LINE type products, are playing an important role at the earliest stages of mammalian development. Larsson and colleagues have pioneered the study of HERVs in human embryogenesis, showing that ERV-3, one of the three viruses involved in placentation, is also highly expressed in many human foetal tissues, including adrenal cortex, kidney tubules, tongue, heart, liver and central nervous system.…”