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Spatiotemporal "time-table" of ways of cell reproduction (mitosis, restitutional mitosis, endomitosis, endoreduplication) of trophoblast cell populations is described. The populations of mitotically active trophoblast cells (diploid and low-polyploid) are located mostly out of contact with maternal tissues. In rodent placenta they mainly switch from mitotic cycle to polyploidizing (restitutional) mitoses and reach 4c-8c. Thereafter they switch to endoreduplication and reach 16c-64c. Following a series of endoreduplication cycles a part of this cell population sets apart and penetrates deeply into the decidualized endometrium and myometrium, their capabilities for replication being lost progressively (in rodent--256c-1024c). The invasive trophoblast cells that reach 256c-1024c via endoreduplication simultaneously form a barrier between semiallogenic fetal and maternal tissues. Arrest of mitoses and complete repression of DNA replication after a series of endoreduplication cycles makes hardly probable the renewal of mitotic activity in the deeply invading tertiary giant trophoblast cells, thereby preventing the possibility of their ectopic expanding in the maternal tissues during the normal pregnancy.

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The trophoblast cells that take part in placenta formation are characterized by different modes of multiplication of their genome that largely designates their eu‐ or aneuploidy level. The two main ways of genome multiplication are described in different degree: (a) endoreduplication that involves almost complete shutdown of mitosis and (b) reduced mitosis (‘endomitosis’) in which, by contrast, entry into mitosis and the passage of its initial stages is a prerequisite of genome multiplication. Endoreduplication observed in the trophoblast giant cells (TGC) in a range of mammalian species implies uncoupling of DNA replication from mitosis achieved by reduction of mitotic Cdk activity. The key role in the regulation of endoreduplication and endomitosis play activity of APC/C complex, geminin and E2F family. A programme of genome multiplication and cell cycle progression may include depolyploidization achieved by specific mitotic or non‐mitotic (amitotic) division of the giant nucleus. In some mammalian species (Rodents), this process represents the final step of the giant cell lifespan that coincides with complete cessation of cell or genome reproduction. Meantime, in other species the process may take part in cell reproduction during lengthy pregnancy. The dynamics of fox and human polyploidization is similar by the possibility of a simultaneous increase in the proportion of endopolyploid and low‐polyploid cells. Reduced mitoses, endoreduplication and depolyploidization appear to be an evolution strategy allowing to generate the functionally different trophoblast cell populations depending of the lifestyle of life of the animal species. Some placental pathologies may be accounted for disturbance of the programme of the cell/genome reproduction of the giant and low‐ploid cell populations.

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