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• W2148528862 abstract "Mutations in the gene encoding the cholesterol biosynthetic enzyme NSDHL are associated with the X-linked male-lethal bare patches (Bpa) mouse. Mutant male embryos for several Nsdhl alleles die in midgestation with placental insufficiency. We examined here a possible role of the maternal genotype in such placental pathology. Pre-pregnancy plasma cholesterol levels were similar between wild-type (WT) and Bpa1H/+ dams fed a standard, cholesterol-free diet. However, there was a marked decrease in cholesterol levels between embryonic day (E)8.5 and E10.5 for both genotypes. Further, there was a significant lag between E11.5 and E13.5 (P = 0.0011) in the recovery of levels in Bpa1H/+ dams to their pre-pregnancy values. To investigate possible effects of the maternal genotype on fetal placentation, we generated transgenic mice that expressed human NSDHL and rescued the male lethality of the Bpa1H null allele. We then compared placenta area at E10.5 in WT and Bpa1H/+ female embryos where the mutant X chromosome was transmitted from a heterozygous mother or a rescued mutant father. In mutant conceptuses, placental areas were ∼50% less than WT. Surprisingly, expression of Nsdhl in trophoblast lineages of the placenta and yolk sac endoderm, which occurs only from the maternally inherited allele in a female embryo, had the largest effect on placental area (−0.681 mm2; P < 0.0001). The maternal genotype had a smaller effect, independent of the fetal genotype (−0.283 mm2; P = 0.024). These data demonstrate significant effects of the mother and fetal membranes on pregnancy outcome, with possible implications for cholesterol homeostasis during human pregnancy." @default.
• W2148528862 created "2016-06-24" @default.
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• W2148528862 date "2009-11-11" @default.
• W2148528862 modified "2023-10-14" @default.
• W2148528862 title "Significant contributions of the extraembryonic membranes and maternal genotype to the placental pathology in heterozygous Nsdhl deficient female embryos" @default.
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• W2148528862 doi "https://doi.org/10.1093/hmg/ddp502" @default.
• W2148528862 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2796896" @default.
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