Table 4.
Comparison of placentation across different research models.
| Model | Type of placentation | Gestation length (days) | Advantages | Limitations |
|---|---|---|---|---|
| Human | • Hemochorial | 280 | • Maternal plasma readily accessible | • Difficult to control environment factors |
| • Discoid • Villous organization and extensive spiral artery remodeling • Interstitial extravillous trophoblast invasion | • Placenta samples available from a broad spectrum of adverse pregnancy outcomes • Diverse and extensive literature database • Well established in vitro systems (e.g., cell culture, explants, placental perfusion) | • Highly variable genetics • Restrictions to testing treatments/therapeutics • Precise timing of start of pregnancy can be uncertain • Delay in pregnancy detection limits the ability to obtain samples within first few weeks of pregnancy | ||
| • TS cells available [81–83] | ||||
| Macaque monkey | • Hemochorial • Bi-discoid placenta • Extensive endovascular extravillous trophoblast remodeling of decidual spiral arteries | 165 | • Ability to test treatments/therapeutics • Most appropriate model available for human placental physiology, immunology, and endocrine function at the maternal–fetal interface [121, 246, 247] | • Trophoblast interstitial extravillous invasion is superficial in comparison to human • Limited transgenic models • Specialized veterinary expertise and housing required |
| • Placental architecture is highly translational [121] • Offspring are born precocial | ||||
| • Placental transfer of passive immunity | ||||
| • Placental expression of C19MC [203] and nonclassical MHC class I [247] | ||||
| Guinea Pig | • Hemomonochorial • Discoid • Labyrinthine, invasive [141, 169, 248, 249] | 67 | • Offspring born precocial [141, 169, 249] • Blastocyst is completely encapsulated within the decidua, similar to human [248] | • Dearth of available antibodies • Lack of transgenic models |
| • Passive immunity in late term [250] | ||||
| • Substantial trophoblast invasion [5] | ||||
| • Similar steroid production and metabolism in the decidua and fetal membranes as the human [169] | ||||
| Rabbit | • Hemodichorial • Discoid • Labyrinth organization [125, 169] | 32 | • Fully sequenced genome [122] • Induced ovulator allowing for timed matings [122] • Offspring born precocial [172] | • Placental endocrinology is different than human [169] • Dearth of available antibodies |
| • Passive immunity in late term [250] • Housing facilities are readily available | ||||
| Mouse | • Hemotrichorial | 20 | • Facile manipulation of genetics [122] | • Offspring not born precocial |
| • Discoid • Labyrinthine organization and some spiral artery remodeling [125] | • Ability to test treatments/therapeutics • Timed mating • NK cells present at MFI as with human [251] • Ability to perfuse mid and late gestation placentas [85] • TS cells available [85, 252] | • Placental organization, cell types, and endocrine profile differ compared to humans [253–255] • PLAP is not expressed • Blood flow to the placenta is more limited than in human [121] • Lack of nonclassical MHC expression [251, 256] | ||
| • Shallow implantation compared to rat or human [251] | ||||
| • Placental expression of C19MC miRNA is not conserved [203] | ||||
| • TS cell isolation and propagation differ from primate [81–84, 257] | ||||
| • Murine cytotrophoblast cells are in direct contact with maternal blood, whereas syncytiotrophoblasts are in direct contact in the human [98] | ||||
| Rat | • Hemotrichorial | 22 | • Nonclassical MHC expression [251, 256] | • Offspring not born precocial |
| • Discoid • Labyrinthine organization • Deep placental implantation [251, 258] | • NK cells at MFI as human [251] • larger size compared to mouse allows practical advantages (tissue availability, surgical procedures) • TS cells available [85, 259] | • Different placental organization and cell types compared to humans [258] • Placental expression of C19MC miRNA is not conserved [203] | ||
| • Less extensive genetic technology and antibody development compared to the mouse [122] | ||||
| • Different endocrine profile than humans [255] | ||||
| Sheep | • Epitheliochorial (synepitheliochorial) | 150 | • Relatively few offspring per liter [5, 260] | • Minimal trophoblast invasion [260] |
| • Cotyledonary [250] | • Offspring born precocial [122] • Large blood samples and surgical manipulations including chronic instrumentation of the fetus are feasible | • Practical limitations on housing of research animals and length of gestation • Different placental cell types and endocrine profile than humans [255] | ||
| Cattle | • Epitheliochorial (synepitheliochorial) | 280 | • Sites of nutrient and waste exchange are villous [124] | • Minimal trophoblast invasion [260] |
| • Cotyledonary • Partially nondeciduate [103, 261, 262] | • Macrophages located at the maternal–fetal interface at low levels during the first two-thirds of pregnancy and increase substantially by term [261] • Nonclassical MHC expression towards the end of pregnancy [263] | • Practical limitations on housing of research animals and length of gestation • Different placental cell types and endocrine profile than humans [255] | ||
| • TS cells available [264] | ||||
| • Large blood samples and surgical manipulations are feasible | ||||
| Pig | • Epitheliochorial • Diffuse [262] | 114 | • Fully sequenced genome [260] • Placental attachment is superficial and interdigitates with the highly folded maternal endometrium • TS cells available [265] • Large blood samples and surgical manipulations are feasible | • Fetal nutrition is predominantly acquired through uterine gland secretions • Passive immunity does not occur until after birth [250] • Unlike humans, there is no syncytiotrophoblast cell type [124] • Practical limitations on housing of research animals and length of gestation |