Tamoxifen administration in pregnant mice can be deleterious to both mother and embryo.

Nikita Ved,Duncan Burnaby Sparrow,Angela Curran,Frances Mary Ashcroft

doi:10.1177/0023677219856918

Abstract

Since it was introduced 20 years ago, tamoxifen-inducible genetic recombination in vivo has become a standard tool in many fields. This technique has great utility, allowing precise temporal and spatial gene recombination mediated by expression of a Cre recombinase-oestrogen receptor hormone binding domain fusion protein. It is frequently used in developmental biology, either for accurate spatio-temporal gene deletion or for lineage-labelling. Administration of high doses of tamoxifen can rapidly induce abortion in pregnant mice but this can be partially overcome by progesterone co-administration. However, administration of tamoxifen to pregnant mice early in pregnancy may have potentially lethal effects on the mother independently of abortion, and can also severely perturb embryonic development. Despite this, only a few published studies mention this fact in passing, and standard parameters for successful or unsuccessful use of tamoxifen in pregnant mice have not been reported. Therefore, in the interests of providing a framework for more humane animal research, we describe our experiences of tamoxifen administration during early gestation in mice. These observations should assist the design of future studies in accordance with the principles of the three Rs (Replacement, Reduction and Refinement of Animals in Research).

Highlights

Since it was introduced 20 years ago, tamoxifen-inducible genetic recombination in vivo has become a standard tool in many fields
Tamoxifen is metabolized in vivo to 4-hydroxy-tamoxifen, which acts as an antagonist of the oestrogen receptor
They were housed in a specific-pathogen-free facility free from the major rodent pathogens except Helicobacter hepaticus, with a 12:12 h light:dark cycle, at 19–23C, 55% Æ 10% humidity, in individually-ventilated cages (Tecniplast UK Ltd, Rushden, UK) containing Grade 4 Aspen Chip bedding (Datesand Ltd, Manchester, UK), cardboard tunnels and Sizzle Pet nesting material (LBS Biotechnology, Horley, UK), with free access to Teklad

Summary

Introduction

Since it was introduced 20 years ago, tamoxifen-inducible genetic recombination in vivo has become a standard tool in many fields. Five to seven days after plugging, the pregnant females were injected subcutaneously into the scruff on one occasion with a single dose of 10–200 mg/kg tamoxifen (Sigma-Aldrich, Gillingham, UK) dissolved in corn oil (SigmaAldrich, Gillingham, UK; see Table 1 for study design). The mice did not carry a Cre-ERT2 allele, so tamoxifen treatment would have no effect on the maternal genome.

Results

Conclusion