Fetal cell-free DNA circulates in the plasma of pregnant mice: relevance for animal models of fetomaternal trafficking.
BACKGROUND
Cell-free fetal DNA (fDNA) can be detected in maternal plasma throughout human pregnancy and is rapidly cleared after delivery. fDNA measurement has clinical application in many complications of pregnancy. Our aim was to determine if fDNA could be detected in maternal plasma during pregnancy in a mouse model system. We then compared the levels of fDNA during pregnancies in which the mother and fetus were either congenic or allogenic.


METHODS
C57BL/6J (H-2b) or DBA/2J (H-2d) wild-type female mice were mated to C57BL/6J mice transgenic for the enhanced green fluorescent protein (gfp) and sacrificed while pregnant. C57BL/6J female mice that had previously given birth to three to six litters after mating with transgenic males were sacrificed after delivery. We used real-time quantitative PCR amplification to detect and measure gfp sequences in maternal plasma.


RESULTS
fDNA was consistently detected in maternal plasma during pregnancy and was always absent after delivery [median 211 genome equivalents (GE)/ml vs 0 GE/ml, respectively, P=0.0001]. The level of fDNA was higher in allogenic matings compared to congenic matings (median 167 GE/ml/GFP + fetus vs 81 GE/ml/GFP + fetus, respectively).


CONCLUSIONS
fDNA sequences can be reliably detected in maternal plasma during murine pregnancy. Our data lends further support to the use of nonhuman species to investigate the mechanisms involved in fetomaternal trafficking.
Division of Genetics, Departments of Pediatrics and Obstetrics and Gynecology, Tufts-New England Medical Center, Boston, MA, USA.
Kiarash
K
Khosrotehrani
Tuangsit
T
Wataganara
Diana W
DW
Bianchi
Kirby L
KL
Johnson
D000818:Animals; D002474:Cell-Free System; D004247:DNA / Q000032:analysis / Q000097:blood*; D005260:Female; D005865:Gestational Age; D049452:Green Fluorescent Proteins / Q000097:blood / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy / Q000097:blood* / Q000235:genetics*
D049452:Green Fluorescent Proteins; D004247:DNA