Deficiency of Placental Copy Number Variations in Recurrent Pregnancy Loss Patients

Background: Recurrent pregnancy loss (RPL) concerns ~3% of couples aiming at childbirth and idiopathic RPL represents ~50% of cases. Abnormal placental development and function leading to obstruction of the feto-maternal communication is an important cause of adverse pregnancy outcome. Our seminal study revealed an extensive load of somatic copy number variations (CNVs) in the human placental genome with the highest fraction found in the placentas representing normal gestation¹.

Objective: We aimed to study the role of placental CNVs in RPL under two hypothesis (i) insufficient fraction of somatic genomic rearrangements impairs the function of placental genome; (ii) risk CNVs involving genes critical for early (extra-)embryonic development lead to miscarriage.

Methods: We compared CNV profiles of idiopathic RPL cases (mother-father) and placental samples with normal, uncomplicated pregnancies. CNV calling pipeline included genome-wide genotyping (Illumina) followed by bioinformatics combining alternative CNV calling algorithms.

Results: Consistent with the hypothesis, placental genomes of RPL cases exhibited minimal amount of rearrangements compared to successful pregnancies. The number of CNVs was close to the estimates for parental blood DNA. Additionally, overrepresentation of large pericentromeric and subtelomeric CNVs in parental genomes was detected as risk factor for RPL.

Conclusion: Our data give support that rapid placental development may need large and simultaneously occurring genomic rearrangements to guarantee active proliferation, migration and invasion of trophoblastic cells.

References:

¹Kasak, L et al. Extensive load of somatic CNVs in the human placenta. Sci. Rep. 5, 8342 (2015)