Uterine signaling at the emergence of the embryo from obligate diapause

Abstract

Embryonic diapause is the reversible arrest of embryo development prior to implantation under a regime of uterine control that is not well understood. Our objective was to explore uterine modifications associated with the emergence of embryonic diapause in the mink, a species in which embryonic diapause characterizes every gestation. We investigated the uterine transcriptome at reactivation using the suppressive subtractive hybridization technique. A library of 123 differentially expressed genes between uteri with blastocysts in diapause and reactivated blastocysts was generated. Among those genes, 41.5% encode for potential secreted products that are implicated in regulation of cell proliferation (14%), homeostasis (14%), protein folding (11%), electron transport chain (8%), and innate immune response (8%), therefore suggesting that these biological processes are implicated in blastocyst reactivation. Two genes, the high-mobility group nucleosome binding domain 1 ( HMGN1), a chromatin remodeling factor, and the secreted protein acidic and cystein-rich ( SPARC), which is implicated in extracellular cell-cell interactions, were submitted to more detailed analysis of expression patterns in the mink uterus at blastocyst reactivation. Expression of both HMGN1 and SPARC was increased significantly in the uterus at embryo reactivation compared with diapause, principally in the endometrial epithelium and subepithelial stroma. These results provide new insight into uterine signaling at the emergence of the blastocyst from diapause and highlight the factors HMGN1 and SPARC as potential inductors of uterine environment modifications underlying uterine signaling during emergence of the embryo from embryonic diapause.

Hmgn1 acts downstream of C/EBPβ to regulate the decidualization of uterine stromal cells in mice

“…Although it has been reported that Hmgn1 was expressed in the uterus, 17 the detailed expression patterns of Hmgn1 in mouse uterus during early pregnancy have not been described. We thus performed in situ hybridization to localize the distribution of Hmgn1 mRNA in mouse uterus.…”

Embryonic diapause: development on hold

“…Blockade of Odc1 conversion of ornithine to the polyamine putrescine by the suicide inhibitor difluoromethyl ornithine (DFMO) prevents implantation in the mouse (Zhao et al, 2008) and reversibly arrests development in mink (Lefevre et al, 2011b) and mouse (Zwierzchowski et al, 1986) embryos. Expression of ODC1, along with the polyamine availability genes (Lefevre et al, 2011a) and uterine content of the polyamine putrescine (Lefevre et al, 2011b), are upregulated at the termination of diapause in the mink (Murphy, 2012).…”

Select Nutrients in the Uterine Lumen of Sheep and Pigs Affect Conceptus Development

“…For example, Arg can be converted to ornithine by arginase and ornithine converted to putrescine, a polyamine, by ODC1 [16]. Polyamines stimulate proliferation and migration of trophectoderm cells and are required for the transition of mink blastocysts in delayed implantation to an activated state for expansion and implantation [17,18]. Arg can also be metabolized by NOS to NO that stimulates proliferation …”