An Investigation of conceptuses with placental chromosomal mosaicism for the presence of germline mosaicism

Confined placental mosaicism (CPM) is detected in approximately 1-2% of viable pregnancies and has been defined as a dichotomy between the chromosomal constitution of the placental and embryonic/fetal tissues. An investigation for the presence of trisomy in the germ cells was initiated in cases diagnosed with CPM since we suspect that the stroma of the placenta and the primordial germ cells (PGCs) have a common developmental origin. Placental and fetal tissues from one conceptus diagnosed with CPM for trisomy 7 and two conceptuses with CPM for trisomy 16, were analyzed using fluorescence in situ hybridization (FISH). Post-termination conventional cytogenetic analysis of amnion and chorionic stroma from case 1 showed only diploid cells in the amnion and mosaicism for trisomy 7 in the stroma. FISH analysis of formalin fixed - paraffin embedded tissues showed significant levels of trisomy in the placenta while all fetal tissues analyzed including testis were diploid. For Case 2, high levels of trisomy 16 were detected using FISH in both chorionic stroma and cytotrophoblast of the placenta while fetal somatic tissues where diploid. FISH analysis of meiotic oocytes showed significant levels of trisomy 16. In case 3, prenatal metaphase analysis of cytotrophoblast and stroma from chorionic villus sampling showed only 47,XX,+16. Culture of placental vill i after termination showed only trisomy 16 while cultures of multiple fetal tissues showed no evidence of trisomy. FISH analysis of formalin fixed - paraffin embedded lung and meiotic oocytes also failed to show evidence of trisomy 16. The results from Case 2 suggest that conceptuses diagnosed with mosaicism in the chorionic stroma are at risk of exhibiting chromosomal mosaicism in their germ cells. Future studies in similar cases are needed to understand the effects this may have on human fertility in the reproductive period.Medicine, Faculty ofMedical Genetics, Department ofGraduat