Desmoglein-2 during pregnancy and its role in the evolution of viviparity in a marsupial (Sminthopsis crassicaudata; Dasyuridae)

Abstract

Attachment of the blastocyst and formation of the placenta during pregnancy is dependent on structural and cellular changes occurring in the uterine epithelium and in particular to the plasma membrane of these uterine cells. Desmosome expression decreases during pregnancy in eutherians and some squamates, presumably allowing for remodeling of the uterine epithelium and invasion of the trophoblast during implantation. Marsupials are a distinct mammalian amniote lineage of viviparity, with a short implantation or attachment period and varying levels of invasive placentation. To test the generality of changes to the uterine epithelium during pregnancy across mammals, we characterized the distribution of desmosomes in the uterine epithelial cells of a marsupial, Sminthopsis crassicaudata, using electron microscopy and immunohistochemistry. The absolute number of desmosomes along the lateral plasma membrane decreases during pregnancy and desmosomes are redistributed towards the apical region of the lateral plasma membrane as pregnancy proceeds, similar to what occurs during pregnancy in eutherian mammals. Despite the lower level of maternal investment in pregnancy and the noninvasive structure of fetal membranes in marsupials there are similarities in number and redistribution of desmosomes along the plasma membrane and changes to the morphology of the uterine epithelial cells suggesting that similar plasma membrane changes occur across all lineages of amniote vertebrates.

Dynamic changes to claudins in the uterine epithelial cells of the marsupial Sminthopsis crassicaudata (Dasyuridae) during pregnancy

“…Nineteen adult S. crassicaudata were used in this study (five nonpregnant and 14 pregnant). All animals were those used by Laird et al () and Dudley et al (), from a breeding colony at The University of Sydney. The animals were euthanized by CO 2 inhalation followed by decapitation.…”

“…The least invasive type of placentation seen in vertebrates is epitheliochorial placentation, which involves embryonic attachment to an intact uterine epithelium (Carter & Enders, ). Irrespective of placental invasiveness, the plasma membrane transformation has been demonstrated during early pregnancy in species from all viviparous amniote lineages: reptiles, marsupial mammals, and eutherian mammals (Hughes, ; Roberts & Breed, ; Dudley, Murphy, Thompson, & McAllan, ; Dudley, Murphy, Thompson, & McAllan, ; Dudley, Murphy, Thompson, Carter, & McAllan, ; Laird et al, ; Laird, Thompson, Murphy, & McAllan, ; Murphy, ). Hence, the plasma membrane transformation appears to be a necessary process for uterine receptivity across viviparous amniotes with varying modes of placentation (Murphy, ).…”

“…Modifications to the junctional complexes that laterally connect uterine epithelial cells together are key processes involved in the plasma membrane transformation that are conserved in marsupials and eutherians (Dudley et al, , , 2018c; Illingworth et al, ; Laird et al, ). Lateral junctional complexes include tight junctions, the adherens junction, and desmosomes (Farquhar & Palade, ).…”

“…During early pregnancy in eutherian mammals and a marsupial species, Sminthopsis crassicaudata , tight junctions extend down the lateral plasma membrane of uterine epithelial cells, which likely functions to increase the barrier properties of the tight junction and decrease the paracellular permeability between adjacent epithelial cells (Laird et al, ; Murphy, ). Conversely, immediately beneath the tight junction, the adherens junction is lost, and desmosomes are apically redistributed and become fewer (Dudley et al, , , 2018c; Illingworth et al, ; Preston, Lindsay, & Murphy, ; Preston, Lindsay, & Murphy, ). Consequently, adherence between uterine epithelial cells is reduced, which may facilitate embryonic invasion into maternal tissues, while the extension of tight junctions ensures the distinct microenvironment in the uterine lumen is simultaneously maintained (Illingworth et al, ; Laird et al, ; Murphy, ).…”

“…In S. crassicaudata , an endotheliochorial placenta forms around Day 10 of a 13.5‐day pregnancy (Roberts & Breed, ). As in rats, uterine epithelial cell‐cell adhesion is reduced by loss of the adherens junction and apical redistribution of desmosomes along the lateral plasma membrane (Dudley et al, ; ). Given that tight‐junction depth and occludin distribution suggest the paracellular pathway becomes more regulated in the preimplantation period of S. crassicaudata (Laird et al, ), we predicted that barrier‐forming claudins (1, 3, 4, and 5) will also redistribute to the tight‐junction region of uterine epithelial cells during pregnancy.…”