Abstract
During the course of a study aiming to obtain a tetracycline (Tet)-inducible transgene expression restricted to the placenta, we have observed a toxicity of doxycycline (dox) given in the food at doses of 2.5–10 mg/g to pregnant mice from two different inbred strains. During the second half of gestation, dox-fed non-transgenic mice presented placental anomalies and impaired fetal development proportional to the dose of antibiotic. Thus, dox administered in commonly used food doses can have an adverse effect on pregnancy. These observations are important for studies of placental or fetal development using inducible gene promoters.
Similar content being viewed by others
References
Boucher D (1969) Abortive properties of tetracyclines in mice. Hormone treatments. Arch Sci Physiol (Paris) 23: 481–516 (in French).
Fedorov LM, Tyrsin OY, Krenn V, Chernigovskaya EV and Rapp UR (2001) Tet-system for the regulation of gene expression during embryonic development. Transgenic Res 10: 247–258.
Hasan MT, Schönig K, Berger S, Graewe W and Bujard H (2001) Long-term, noninvasive imaging of regulated gene expression in living mice. Genesis 29: 116–122.
Kistner A, Gossen M, Zimmermann F, Jerecic J, Ullmer C, Lübbert H and Bujard H (1996) Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci USA 93: 10933–10938.
Kurz H and Wittekind D (2001) A new panoptic stain for developmental biology - the mouse placenta paradigm. Ann Anat 183: 437–441.
Lewandoski M (2001) Conditional control of gene expression in the mouse. Nat Rev 2: 743–755.
Mansuy IM and Bujard H (2000) Tetracycline-regulated gene expression in the brain. Curr Opin Neurobiol 10: 593–596.
Perl AT, Tichelaar JW and Whitsett JA (2002a) Conditional gene expression in the respiratory epithelium of the mouse. Transgenic Res 11: 21–29.
Perl AK, Wert SE, Nagy A, Lobe CG and Whitsett JA (2002b) Early restriction of peripheral and proximal cell lineages during formation of the lung. Proc Natl Acad Sci USA 99: 10482–10487.
Rechtman MP, Zhang J and Salamonsen LA (1999) Effect of inhibition of matrix metalloproteinases on endometrial decidualization and implantation in mated rats. J Reprod Fertil 117: 169–177.
Schwarz RH (1981) Considerations of antibiotic therapy during pregnancy. Obstet Gynecol 58: 95S–99S.
Shin MK, Levorse JM, Ingram RS and Tilghman SM (1999) The temporal requirement for endothelin receptor-B signalling during neural crest development. Nature 402: 496–501.
Shlopov BV, Stuart JM, Gumanovskaya ML and Hasty KA (2001) Regulation of cartilage collagenase by doxycycline. J Rheumatol 28: 835–842.
Steiner G, Bradford W and Craig JM (1965) Tetracycline-induced abortion in the rat. Lab Invest 14: 1456–1463.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Moutier, R., Tchang, F., Caucheteux, S.M. et al. Placental Anomalies and Fetal Loss in Mice, After Administration of Doxycycline in Food for Tet-system Activation. Transgenic Res 12, 369–373 (2003). https://doi.org/10.1023/A:1023388903642
Issue Date:
DOI: https://doi.org/10.1023/A:1023388903642