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Abstract

The mammalian embryo and fetus are unable to develop without a well-established, functional placenta. This transitory yet indispensable structure attaches the conceptus to the uterus and establishes the vascular connections necessary for nutrient and gaseous exchange between maternal and fetal compartments. Genetic targeting strategy allows the generation of mice lacking a specific gene. Such approaches reveal: (i) the high incidence of mutant embryonic or fetal death in utero, and (ii) the extraembryonic (placental) causes of these deaths. Due to the similarities presented between mouse and human placenta, we propose to use the potential of mouse targeting experiments as a model in order to understand human obstetrical pathologies. In this paper, we first review genes that have been demonstrated to be required in mice for implantation, choriovitelline and chorioallantoic placentation. Using examples (integrins, homeoboxs, hepatocyte growth factor or epidermal growth factor receptor...) we demonstrate the reality and efficiency of such an approach. Other candidate genes (receptor of leukemia inhibitory factor, Wnt2 or retinoic acid receptor alpha...) in order to understand, prevent and treat human obstetrical pathologies.

Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae

“…Additional studies are required to clarify this point. Among factors known to be critical for in vivo syncytiotrophoblast formation (32,33), the glial cells missing-1 (Gcm1) transcription factor is of special interest, because its pattern of expression is remarkably similar to that of syncytin-A and -B (28). In addition, Gcm1-deficient mice display a failure in labyrinth formation and lack syncytiotrophoblasts (34,35).…”

The Role of Homeobox Genes in the Development of Placental Insufficiency

“…Overwhelming evidence shows they regulate embryonic development [29,30], reproductive processes [31], and developmental growth disorders and cancers [32]. Homeobox genes also control placental development in the human [24,33] and the mouse [34,35,36,37]. Mouse mutants provide genetic proof that altered homeobox gene expression generates placental defects [35,36,37] with the hallmarks of human IUGR [35].…”

“…Homeobox genes also control placental development in the human [24,33] and the mouse [34,35,36,37]. Mouse mutants provide genetic proof that altered homeobox gene expression generates placental defects [35,36,37] with the hallmarks of human IUGR [35]. Most important to this work is that homeobox genes are expressed in two important cell types that malfunction in the human IUGR-affected placenta, trophoblast and endothelial cells.…”

“…Dlx3 and Esx1 mutant mice show specific defects in the labyrinthine trophoblast of the chorioallantoic placenta [38,39]. Other mouse homeobox gene knockouts have provided genetic proof that homeobox genes regulate vascular development and angiogenesis in placental development (reviewed in [35,36,37]). Therefore, in animal model systems, homeobox genes control trophoblast and endothelial cell functions, and altered placental homeobox expression can cause restricted growth of the fetus.…”

Evaluation of Utero-placental and Fetal Hemodynamic Parameters Throughout Gestation in Pregnant Mice Using High-Frequency Ultrasound

“…Indeed, the process of blood flow distribution in fetal organs was originally described in fetal sheep using radiolabeled microspheres (Heymann et al 1977; Heymann and Rudolph 1967; Rudolph and Heymann 1967; Rudolph and Heymann 1972). Recently, other animal models have also been proposed; pregnant murine and rabbit models (Bassan et al 2000; Eixarch et al 2009; Eixarch et al 2011) have shorter gestational periods requiring smaller experimental areas, relatively lower costs, higher number of fetuses, and have similar characteristics as the human placenta (Malassine et al 2003; Sapin et al 2001). The use of knock-out mouse strains provides further advantages in studying the effects of specific genes during pregnancy (Pham et al 2009; Smith et al 2007; Tian et al 2006; Zhang et al 2011).…”