The Macaque Placenta—A Mini-Review

Abstract

As part of an overview of the female reproductive organs in the macaque monkey, the present paper presents normal placental development. Although normally not examined in routine toxicologic pathology, the interest in the macaque as a model for reprotoxicity studies is increasing significantly. Based on different classifications, the macaque placenta belongs to the chorioallantoic, (bi)discoid, villous, deciduate, and hemochorial placental type. Within the first fourteen days after fertilization, a large number of events subsequently occur (apposition, adhesion, penetration and traversal of trophoblasts, blood vessel penetration, and development of villi). After this period, the basic placental structure has been laid down in the endometrium, and the initial communication between mother and fetus has been established. Further expansive growth of the placenta and development of anchoring villi are believed to be accomplished by continuous proliferation and migration of the trophoblasts from the trophoblastic shell. Despite the same function of human and macaque placentas, the morphologic structure and developmental timelines are different. Possible toxicological and physiological implications of these differences toward the value of macaques within reprotoxicity studies is discussed at the end of this paper. Besides a transporting role between mother and fetus, the placenta is also an endocrine organ that synthesizes a variety of hormones and cytokines. They influence ovarian and uterine physiology at the start of pregnancy and fetal and mammary physiology during gestation and around labor, respectively.

Maternal CD4 + T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission

“…However, preclinical vaccine studies that have shown significant reduction in the rate of congenital infection and pup mortality in guinea pigs have not often predicted the outcome of human trials, a likely reflection of the evolutionary differences of both the species and the species-specific CMV (7-10). Our development of a rhesus monkey model of congenital CMV transmission that is more physiologically similar to humans in reproductive and placental biology (44) and uses a more genetically related CMV to that of humans than small-animal models (17,18) provides the field with a highly relevant tool that may better predict preclinical efficacy of vaccine candidates. In addition, given the availability of vast resources to evaluate the rhesus immune response, the rhesus monkey congenital CMV model may allow more rigorous analysis of the maternal immune correlates of protection against congenital CMV infection, including the role of cell-mediated immunity that could inform a protective vaccine.…”

The pentameric complex of human Cytomegalovirus: cell tropism, virus dissemination, immune response and vaccine development

“…Finally, a neutralizing mAb to gH/gL was found to be protective in the guinea pig model of congenital infection [121]. However, concerns have been raised about the ability of the guinea pig model to predict the outcome of clinical trials [98,122].…”

Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys

“…Furthermore, we hypothesize that this NHP model may more accurately reflect HCMV pathogenesis than small-animal models owing to increased similarity of host and virus. The rhesus monkey placenta is anatomically, physiologically, and immunologically quite similar to that in humans, which likely enhances the translational applications of the model (25). Additionally, RhCMV is genetically more homologous to HCMV than guinea pig or murine CMV (24,26,27) and employs highly conserved immune-evasion pathways including viral IL-10 (28) and MHC downregulation (29).…”