Uterine Gene Expression in the Live-Bearing Lizard, Chalcides ocellatus, Reveals Convergence of Squamate Reptile and Mammalian Pregnancy Mechanisms

Abstract

Although the morphological and physiological changes involved in pregnancy in live-bearing reptiles are well studied, the genetic mechanisms that underlie these changes are not known. We used the viviparous African Ocellated Skink, Chalcides ocellatus, as a model to identify a near complete gene expression profile associated with pregnancy using RNA-Seq analyses of uterine transcriptomes. Pregnancy in C. ocellatus is associated with upregulation of uterine genes involved with metabolism, cell proliferation and death, and cellular transport. Moreover, there are clear parallels between the genetic processes associated with pregnancy in mammals and Chalcides in expression of genes related to tissue remodeling, angiogenesis, immune system regulation, and nutrient provisioning to the embryo. In particular, the pregnant uterine transcriptome is dominated by expression of proteolytic enzymes that we speculate are involved both with remodeling the chorioallantoic placenta and histotrophy in the omphaloplacenta. Elements of the maternal innate immune system are downregulated in the pregnant uterus, indicating a potential mechanism to avoid rejection of the embryo. We found a downregulation of major histocompatability complex loci and estrogen and progesterone receptors in the pregnant uterus. This pattern is similar to mammals but cannot be explained by the mammalian model. The latter finding provides evidence that pregnancy is controlled by different endocrinological mechanisms in mammals and reptiles. Finally, 88% of the identified genes are expressed in both the pregnant and the nonpregnant uterus, and thus, morphological and physiological changes associated with C. ocellatus pregnancy are likely a result of regulation of genes continually expressed in the uterus rather than the initiation of expression of unique genes.

Embryo implantation evolved from an ancestral inflammatory attachment reaction

“…The immune consequences of pregnancy appear to be milder in viviparous reptiles, in which some specific interleukin genes appear to be down-regulated and no whole-scale up-regulation of inflammatory markers has been observed (19,63,64). This difference could be caused, in part, by the absence of an invasive trophoblast or other properties of the chorionic tissue unique to mammals and not associated with the evolution of viviparity (65,66).…”

The evolution of viviparity: molecular and genomic data from squamate reptiles advance understanding of live birth in amniotes

“…Placental transport of iron has only been reported in highly placentotrophic Mabuya skinks (Ramirez-Pinilla 2006, Ramirez-Pinilla et al 2011), does not occur in lecithotrophic Thamnophis snakes (Hoffman 1970), but has not been investigated in other species (Thompson 1982. The mechanisms of inorganic ion transport are largely unknown in viviparous squamates, but in snakes of the genus Thamnophis, sodium may be transported by the yolk-sac placenta to increase osmolarity of the embryo and to facilitate water absorption , Blackburn & Lorenz 2003 Brandley et al 2012). Thus, nutrient transport is controlled by a large suite of genes, yet we still lack information whether these same genes are also used by other viviparous or oviparous squamates.…”

“…Recent advances in next-generation sequencing has been poised to significantly advance our understanding of the oviparity to viviparity transition in squamates (e.g. Brandley et al (2012)) because we now have the ability to uncover the genetic mechanisms that underlie the morphological and physiological changes associated with viviparity and complex placentation.…”

“…Finally, advances in molecular techniques now allow detailed analysis of gene expression in 'non-model' organisms (e.g. Brandley et al (2012)). Perhaps the greatest advance has been next-generation transcriptome sequencing, which provides the snapshots of nearly all the genes expressed in a tissue and allows direct comparisons of molecular function amongst squamate lineages and between squamates and mammals.…”

Biología reproductiva y placentotrofía en lagartijas del género Mabuya

“…Los mecanismos moleculares de transporte de nutrientes son relativamente bien conocidos en mamíferos euterios y solo han sido investigados en lagartijas placentotróficas no extremas (Pseudemoia entrecasteauxii, P. spenceri, y Chalcides ocellatus, Biazik et al, 2009;Brandley et al, 2012;Griffith et al, 2013a, b). ¿Son los mecanismos de transporte de nutrientes similares entre clados que evolucionaron la placentotrofía de manera convergente?…”