Developmental expression of Ki‐67 antigen and proliferating cell nuclear antigen in macaque placentas

Abstract

Placental growth is largely determined by the proliferation of cytotrophoblast cells. However, the distribution of cytotrophoblast cells engaged in the cell cycle during placental development is poorly understood. Recently, antibodies have been developed that identify two proteins directly involved with DNA synthesis: Ki-67 protein and proliferating cell nuclear antigen (PCNA). Immunolocalization of Ki-67 and PCNA provides a measure of the proliferating cells in tissues. We examined, in macaque placentas, the spatiotemporal pattern of expression of these proteins during gestation. Tissues from 24 macaque placentas collected from 22-153 days of pregnancy were prepared for paraffin sections. Standard immunoperoxidase techniques were used to identify Ki-67 and PCNA. The proteins generally co-localized, although PCNA was usually represented in more cells than Ki-67. Early in gestation the cell columns contained many labeled cells. The cytotrophoblastic shell was occupied by numerous cells with PCNA positive nuclei, but few were reactive for Ki-67. By 45 days of pregnancy the immunolabeled cells in the cell columns were concentrated in the proximal regions, adjacent to the anchoring villus tips. The number of positive cells decreased by 100 days when the cell columns were diminished, leaving the anchoring villus tips buried in the shell. Labeled cells were rarely present in the shell at late pregnancy. The single layer of cytotrophoblast cells in the chorionic plate contained numerous reactive cells throughout early and mid-gestation. After approximately 100 days the cytotrophoblast layer of the chorionic plate was stratified over large areas. Soon thereafter few cells of the chorionic plate were labeled. The chorionic villi contained reactive cytotrophoblastic cells throughout gestation. Extravillous cytotrophoblast cells invading spiral arteries were sometimes labeled for PCNA but not Ki-67. We conclude that compartments of the placenta are distinguished by specific patterns of cytotrophoblast cell proliferation. Moreover, these patterns correspond to macroscopic growth parameters of the placenta. Evidence suggests that the macaque placenta slows its rate of diametrical growth at approximately 100 days of gestation. It is at about this time that the cell columns are absorbed into the trophoblastic shell and this pool of proliferating cells is diminished. The growth in diameter of the chorionic plate matches that of the shell. In this compartment also the architecture changes at about 100 days as the cytotrophoblast layer stratifies. This stratification may result from continued proliferation of cytotrophoblast cells when the diametrical rate of growth is decreasing. Soon thereafter, proliferation decreases in this compartment also. By contrast, labeled cells were found in chorionic villi throughout gestation.(ABSTRACT TRUNCATED AT 400 WORDS)