Proliferation and growth factor expression in abnormally enlarged placentas of mouse interspecific hybrids

Abstract

It has been shown previously that abnormal placental growth occurs in crosses and backcrosses between different mouse (Mus) species. In such crosses, late gestation placentas may weigh between 13 and 848 mg compared with a mean placental weight of approximately 100 mg in late gestation M. musculus intraspecific crosses. A locus on the X-chromosome was shown to segregate with placental dysplasia. Thus in the (M. musculus ؋ M. spretus)F1 ؋ M. musculus backcross, placental hyperplasia cosegregates with a M. spretus derived X-chromosome. Here we have investigated whether increased cell proliferation and aberrant expression of two genes that are involved in placental growth control, Igf2 and Esx1, may cause, or contribute to placental hyperplasia. Increased bromodeoxyuridine labeling of nuclei, reflecting enhanced proliferation, was indeed observed in hyperplastic placentas when compared with normal littermate placentas. Also, increased expression of Igf 2 was seen in giant cells and spongiotrophoblast. However, when M. musculus ؋ M. spretus F1 females were backcrossed with males that were heterozygous for a targeted mutation of the Igf 2 gene, placentas that carried a M. spretus derived X-chromosome and were negative for a functional Igf 2 allele exhibited an intermediate placental phenotype. Furthermore, in early developmental stages of placental hyperplasia, we observed a decreased expression of the X-chromosomal Esx1 gene. This finding suggests that abnormal expression of both Igf 2 and Esx1 contributes to abnormal placental development in mouse interspecific hybrids. However, Esx1 is not regulated by IGF2.

Molecular and morphologic analyses of expression of ESX1L in different stages of human placental development

“…A decreased expression of the X-chromosomal Esx1 gene was detected in abnormally enlarged placentas of mouse interspecif hybrids [13]. Moreover, further investigation of gene expression with interspecies hybridization, cloning by nuclear transfer, and mutation of the Esx1 gene revealed that genes whose expression is altered in abnormal placental growth are likely to be important in the occurrence of placentopathies [14].…”

Dexamethasone-induced intrauterine growth restriction impacts the placental prolactin family, insulin-like growth factor-II and the Akt signaling pathway

“…Interestingly, dysmorphic development of spongiotrophoblast cells is also a characteristic of interspecies hybrid and cloned placentas (Rogers & Dawson 1970, Zechner et al 1996, Kurz et al 1999, Tanaka et al 2001. Abnormalities in genomic imprinting are implicated in these placental pathologies (Zechner et al 2002, Schutt et al 2003, Shi et al 2004, Singh et al 2004. There is some evidence for imprinting among members of the placental PRL family in Peromyscus (Vrana et al 2001); however, experimentation on imprinting within the rat PRL family locus has not been reported.…”

Cited1 Is Required in Trophoblasts for Placental Development and for Embryo Growth and Survival

“…On the X chromosome, the genetic interval associated with hyperplastic placentas is large (between the centromere and 50 cM) (26). Esx1 (57 cM) may represent one of the genes associated with this phenotype since Esx1 mutants have a hyperplastic placenta and the expression of Esx1 is reduced in the placentas of interspecific hybrids (35,77). It would be interesting to examine the expression of Cited1 in the placentas of interspecific hybrids since the gene is located at 40.1 cM and there is an increase in spongiotrophoblasts in the Cited1 mutant placenta.…”