Alpha-2 Macroglobulin Controls Trophoblast Positioning in Mouse Implantation Sites

Esadeg, Souad; He, Hong; Pijnenborg, Robert; Leuven, Fred Van; Croy, B A

doi:10.1016/s0143-4004(03)00148-6

Cited by 48 publications

(38 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…uNK cells in NOD pregnancy. In NOD.scid (n ϭ 3) and normoglycemic NOD mice (n ϭ 3), uNK cell numbers in the MLAp (site of most uNK cell proliferation) and decidua basalis (site dominated by postmitotic uNK cells) were consistent with published numbers in normal mice (33). Pre-diabetic (n ϭ 3) and diabetic NOD mice (n ϭ 3) had reduced uNK cell numbers in the MLAp (81.9 Ϯ 1.18; 80.8 Ϯ 1.02) compared with NOD.scid mice (87.5 Ϯ 2.22) (P Ͻ 0.05, Fig.…”

Section: Pregnancy Accelerates Progression To Overt Diabetessupporting

confidence: 67%

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

et al. 2007

View full text Add to dashboard Cite

OBJECTIVE-Pregnant diabetic women are at a 4 -12 times higher risk for preeclampsia, an urgent acute-onset complication of mid-to late gestation, than normal pregnant women. Hallmarks of preeclampsia are hypertension, proteinuria, and incomplete modification of endometrial spiral arteries. Transient proangiogenic lymphocytes called uterine natural killer (uNK) cells are implicated in human and rodent spiral artery modification. We studied mid-to late gestations in spontaneously type 1 diabetic NOD mice to investigate whether diabetes alters uNK cell homing and/or function.RESEARCH DESIGN AND METHODS-Normoglycemic, prediabetic, and diabetic NOD mice and controls were mated. Lymphocytes and endometrial endothelium and decidua were studied histologically and in functional assays.RESULTS-Conception accelerated progression to overt diabetes in NOD females who had limited spiral artery development, heavier placentas, and lighter fetuses displaying numerous birth defects compared with controls. UNK cell numbers were reduced in the decidua basalis of diabetic females, whereas interferon-␥ production was elevated. In diabetic NOD mice, decidual expression of the mucosal vascular addressin cell adhesion molecule (MAdCAM)-1 was aberrant in position, whereas vascular cell adhesion molecule (VCAM)-1 expression was reduced. Assays of lymphocyte adhesion to tissue sections under shear forces indicated that diabetes compromises the potential homing functions of both endometrial endothelium and peripheral NK cells.CONCLUSIONS-In diabetes, gestational endometrium has immune and vascular defects that likely contribute to murine fetal loss and birth defects. Analogous problems and preeclampsia in diabetic women may involve similar mechanisms. Diabetes

show abstract

Section: Pregnancy Accelerates Progression To Overt Diabetessupporting

confidence: 67%

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Decidual stromal cells produce many products that inhibit the activity of invasive fetal proteins (30,31), and they produce molecules that signal to uNK cells, which are known to regulate placental invasion in humans among other functions (9)(10)(11)(12). Prolactin is one such product of decidual cells: it has been shown to increase proliferation of uNK cells and increase their cytotoxicity in vitro (6)(7)(8).…”

Section: Discussionmentioning

confidence: 99%

Transformation of a transposon into a derived prolactin promoter with function during human pregnancy

Emera

Wagner

2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Transposable elements (TEs) are known to provide DNA for host regulatory functions, but the mechanisms underlying the transformation of TEs into cis-regulatory elements are unclear. In humans two TEs-MER20 and MER39-contribute the enhancer/ promoter for decidual prolactin (dPRL), which is dramatically induced during pregnancy. We show that evolution of the strong human dPRL promoter was a multistep process that took millions of years. First, MER39 inserted near MER20 in the primate/rodent ancestor, and then there were two phases of activity enhancement in primates. Through the mapping of causal nucleotide substitutions, we demonstrate that strong promoter activity in apes involves epistasis between transcription factor binding sites (TFBSs) ancestral to MER39 and derived sites. We propose a mode of molecular evolution that describes the process by which MER20/MER39 was transformed into a strong promoter, called "epistatic capture." Epistatic capture is the stabilization of a TFBS that is ancestral but variable in outgroup lineages, and is fixed in the ingroup because of epistatic interactions with derived TFBSs. Finally, we note that evolution of human promoter activity coincides with the emergence of a unique reproductive character in apes, highly invasive placentation. Because prolactin communicates with immune cells during pregnancy, which regulate fetal invasion into maternal tissues, we speculate that ape dPRL promoter activity evolved in response to increased invasiveness of ape fetal tissue.cis-regulatory evolution | human evolution | human pregnancy I n the pursuit to understand mechanisms underlying the evolution of gene regulation, it has become increasingly clear that transposable elements play a critical role in regulatory evolution by providing novel genetic elements, including new introns, promoters, enhancers, and insulators (1). In addition to individual examples showing that transposable elements (TEs) are associated with host regulatory function, computational work shows that TEs intersect with many promoter regions (2) and are overrepresented in predicted regulatory regions [(3, 4); see review by Feschotte (1)]. Many questions remain unanswered. How frequently are TEs actually co-opted for regulatory function? What is the adaptive significance of these events? Are TEs used by the host genome immediately upon insertion or do they require extensive sequence evolution before acquiring a biological role? What are the molecular changes that transform a transposable element into a cisregulatory element?In this paper we address the latter two questions posed above by investigating evolution of the decidual prolactin promoter in primates. In a recent paper we showed that the prolactin gene was independently recruited into uterine expression in primates, mice, and elephants by the co-option of different transposable elements, highlighting the frequency at which TEs can be recruited and their importance in gene regulatory innovation (5). Here we trace the evolutionary history and function of transposabl...

show abstract

“…In species with invasive trophoblasts, trophoblasts also effect structural changes on endometrial vessels. For example, trophoblast cells are found in the walls and lumens of human and murine spiral arteries [39,46] and endothelium may be replaced by intravascular trophoblasts that acquire endothelial cell-like molecular expression. It is also possible that distant maternal arterial function is modified by "conducted responses" originating from more proximal interactions between trophoblasts and endothelial or vascular smooth muscle cells and moving rapidly along the vessel wall [47].…”

Section: Trophoblasts In Implantation Site Angiogenesismentioning

confidence: 99%

A Review of Gene Expression in Porcine Endometrial Lymphocytes, Endothelium and Trophoblast During Pregnancy Success and Failure

Tayade

Yuan

Croy

2007

Journal of Reproduction and Development

View full text Add to dashboard Cite

Abstract. Meat pig breeds used commercially in North America lose significant numbers of geneticallynormal fetuses in the peri-implantation (attachment) period and at mid-gestation (day 50 of the114 day gestation interval). Fetal demand that is in excess to the placental blood supply is thought to underlie these waves of fetal loss. In many species, the endometrium of early normal pregnancy is enriched in innate immune cells, particularly uterine natural killer (uNK) cells. In pigs, a species with epitheliochorial placentation, conceptuses mediate about a three-fold enrichment in uNK cells at attachment sites but the functions of these cells are unknown. In species with hemochorial placentation, uNK cells are highly enriched during the process of decidualization and promote endometrial angiogenesis. We have conducted molecular analyses using pure samples of endometrial lymphocytes or endothelium and trophoblast from healthy and arresting conceptus attachment sites in Yorkshire gilts immediately post-attachment [gestation day (GD) 20] and at mid pregnancy (GD50). In healthy sites, angiogenesis was more robustly promoted by lymphocytes than by trophoblasts. An early sign of impending fetal arrest was loss of vascular endothelial growth factor (VEGF) transcription from the lymphocytes and elevation in transcription of the pro-inflammatory gene Interferon (IFN)-γ. We have postulated that newly differentiated endometrial endothelial cells, not fetal trophoblasts, are damaged by the maternal withdrawal of vascular support and onset of inflammation and that this endometrial damage contributes significantly to peri-implantation fetal death.

show abstract

Alpha-2 Macroglobulin Controls Trophoblast Positioning in Mouse Implantation Sites

Cited by 48 publications

References 32 publications

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

Aberrant Endometrial Features of Pregnancy in Diabetic NOD Mice

Transformation of a transposon into a derived prolactin promoter with function during human pregnancy

A Review of Gene Expression in Porcine Endometrial Lymphocytes, Endothelium and Trophoblast During Pregnancy Success and Failure

Contact Info

Product

Resources

About