Abstract
We have previously shown an extensive load of somatic copy number variations (CNVs) in the human placental genome with the highest fraction detected in normal term pregnancies. Hereby, we hypothesized that insufficient promotion of CNVs may impair placental development and lead to recurrent pregnancy loss (RPL). RPL affects ~3% of couples aiming at childbirth and idiopathic RPL represents ~50% of cases. We analysed placental and parental CNV profiles of idiopathic RPL trios (mother-father-placenta) and duos (mother-placenta). Consistent with the hypothesis, the placental genomes of RPL cases exhibited 2-fold less CNVs compared to uncomplicated 1st trimester pregnancies (P = 0.02). This difference mainly arose from lower number of duplications. Overall, 1st trimester control placentas shared only 5.3% of identified CNV regions with RPL cases, whereas the respective fraction with term placentas was 35.1% (P = 1.1 × 10−9). Disruption of the genes NUP98 (embryonic stem cell development) and MTRR (folate metabolism) was detected exclusively in RPL placentas, potentially indicative to novel loci implicated in RPL. Interestingly, genes with higher overall expression were prone to deletions (>3-fold higher median expression compared to genes unaffected by CNVs, P = 6.69 × 10−20). Additionally, large pericentromeric and subtelomeric CNVs in parental genomes emerged as a risk factor for RPL.
Highlights
ACGH approach and identifying a number of CNVs specific to miscarriage events[8]
Placental genomes of recurrent pregnancy loss (RPL) cases exhibited 40% reduction in the number of CNVs compared to normal 1st trimester pregnancies
Our previous study revealed a load of somatic CNVs, especially duplications, in the placental genomes of successful pregnancies[9]
Summary
ACGH approach and identifying a number of CNVs specific to miscarriage events[8]. Two maternally inherited rearrangements included imprinted genes (CTNNA3 and TIMP2) that regulate trophoblast invasion and are normally expressed from only the maternal allele in the placenta. As the highest number of placental CNVs was detected for healthy term pregnancies, we suggested that this phenomenon might be critical for normal gestation. We hypothesized that the placental genomes of recurrent pregnancy loss cases are characterized by insufficient promotion of genomic rearrangements, which may impair early placental development and establishment of a viable pregnancy. We assessed the potential contribution of specific risk CNVs identified in either parental or placental genomes of RPL cases, harbouring genes critical for early development. This is the first report profiling CNVs in the genomes of RPL family trios (mother-father-placenta) and duos (mother-placenta) in comparison to the parental-placental control samples representing uncomplicated early and term pregnancies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
