LAUSR

The human hemochorial placenta is considered a very effective organ of substance transport. The villous mesenchyme is narrow and fetal capillaries with an adequate diameter are located just adjacent to the intervillous space, facilitating smooth fetomaternal substance transfer. In some maternal/fetal disorders, some derangements of this structure are observed, which, however, are not specific. Placental mesenchymal dysplasia (PMD) provides us with a ‘natural experiment’: genome imprinting abnormality is associated with placental morphological abnormalities, such as mesenchymal hyperplasia and dilated fetal vessels. This suggests that the corresponding imprinting genes may be associated with placental morphological development. The placental structure is now being discussed at the gene level. We commend Jitsumori et al. for demonstrating a PMD case and effectively illustrating the associated immunostaining features. Please let us share our thoughts with the readers. They demonstrated the immunostaining of p57kip2, the protein associated with chromosome 11p15.5, which is one of the regions responsible for PMD. In the dichorionic diamniotic placenta, the following three factors were compared: (i) morphologically evident PMD parts; (ii) morphologically normal parts of PMD co-twin; and (iii) normal placenta from the normal co-twin. Interestingly, p57kip2 staining was absent in (i), weak in (ii) and then strongly positive in (iii). Previously, p57kip2 was considered/demonstrated to be absent or weakly stained in macroscopically abnormal placental parts but positive in macroscopically normal parts. This yes/no pattern is considered to characterize the PMD placenta. If we look at Jitsumori et al.’s figure 3c versus 3d, one may consider that this yes/no pattern has been reproduced. However, figure 3e changed this concept. Combining the three figures together, a ‘change in the spectrum’ and not the ‘yes/no pattern’ is evident among (i), (ii), and (iii). Taken together, in the PMD placenta, not only the macroscopically/histologically evident abnormal structural parts but also macroscopically/histologically normal parts show some changes/abnormal staining for corresponding substances. This may be why fetal/neonatal abnormality may not always be consistent with the morphologically evident extent of PMD: morphologically normal parts may also affect the fetus in some cases. Maternal factors affect the placental morphology. Excluding this maternal factor, the twin placenta gave us a ‘natural experiment’. Thus, their study of ‘PMD on twin placenta’ provided ‘double natural experiments’. There are some gene/substance abnormalities corresponding to PMD other than p57kip2. PMD in the co-twin may be a good model for studying the pathophysiology of PMD. Widening this concept, this may be a good model to study placental disorders other than PMD.