In mammals, although size differences exist, most of organs consists of the same cells and exhibits the same structures. However, placentas are quite diverse in cell components, structures and the association between fetal membranes and maternal uteri. These differences have not been well characterized. Recently, endogenous retroviruses (ERVs) have been thought to have caused such diversity, which require both PEG type genes and syncytins.
Placentas are most diverse organs across mammalian species. Although the mammals obtained several new genes specific to pregnancy recognition and/or maintenance, the diversity of placental structures cannot be explained through the expression and functions of functional genes. It has long been thought that viral/transposon components exist in organism’ genomes. In 2000, Mi et al. found that endogenous retrovirus (ERV, Syncytin-1) exists in the human placenta. Since then, syncytin-like structures and their functions have been reported in many animal species [1][2][3], but none of them contain the same nucleotide structures, strongly suggesting that these ERVs are independently captured and integrated into mammalian genomes [4].
Imprinting genes such as those of paternally expressed genes PEG10 [5] and PEG11/RTL1 [6] have been extensively studied and through gene ablation studies, these genes are found necessary for the formation of placental structures [7][8]. Because PEG10 is acquired more than 146 million years ago, PEG10 gene could explain the initial formation of placentas in mammals. However, placental diversity cannot be explained. The researchers have presented recent and related findings that explain how syncytin genes are involved in placental diversity. The researchers presented recent observations on ERVs and how these ERVs control gene expression of both functional genes as well as ERV themselves [9][10]. Based on the recent information, the researchers have presented the baton-pass hypothesis, successive integration of ERVs [11] and new models explaining placental diversity.
Fusogenic activity in the mammalian trophectoderm exhibits a great deal of similarity across species, notwithstanding the huge diversity in placental structures and type of placentation such as invasive (humans and murine) or non-invasive (ruminants). Based on actual experimentation and typical amino acid sequences, their functions are generally limited to fusogenic activity and immunotolerance, which on their own are not sufficient to fully explain the structural diversity of placentas.
Dunn-Fletcher and colleagues (2018) have demonstrated that retroviral THE1B sequence serves as a cis-element for the regulation of corticotropin-releasing hormone (CRH) gene expression. Recently, progress has been made on research into ERV sequences serving as transcriptional and translational regulators [9][10]. These sequences could be co-opted for newly integrated retroviral gene regulation.
Nevertheless, solid confirmation of a retrovirus integration into sperm or egg has not been obtained, and the mechanism of integration remains unclear. The rarity of such events owes in no small part to the narrow windows of possibility for infection, but conversion to active ERVs is also contingent on the perfect confluence of criteria as follows:
In general, the placentas have lower DNA methylation levels than embryos, allowing freer expression of ERVs and transposons during gestation, thereby facilitating selection of advantageous genes from a wider market. Such extraembryonic circumstances might have allowed for not only domestication of ERVs to establish novel endogenous genes via multiple of selections but also the dissemination of ERVs and transposons throughout genomes as transcriptional regulators. Moreover, ERVs could serve as cis- and/or trans-acting factors for functional genes of the host. Similarly, various degrees of maternal-fetal cell interactions in the uterine compartment may have led to change in kinds and degree of gene usage [12], possibly resulting in cellular and morphological changes in placentas. It is interesting to speculate that the placentas themselves might have served as an evolutionary laboratory to promote mammalian evolution [13].
It is now clear that the emergence of mammalian placentas was made possible with the acquisition of therian PEG10 and eutherian PEG11/RTL1 genes, followed by independent, yet successive integrations of syncytin-type genes for structural variations. A question still arises as to whether the placental structures that we know now are the ultimate forms or are still evolving. If the latter is the case, placental structures may still be diversifying and new variations could be awaiting discovery