Introduction: Abnormal fetal growth can cause perinatal morbidity and mortality. The placenta regulates materno-fetal nutrient transfer and secretes hormones with maternal physiological effects. In mice, global loss of insulin-like growth factor 2 (Igf2), a paternally-expressed imprinted gene, causes fetoplacental growth restriction in association with changes in placental transport and endocrine zone (Jz) formation. However, the role of Igf2 in regulating placental endocrine function is unknown. We hypothesised that Igf2 loss in the Jz (Jz-Igf2UE) would impair placental endocrine cell formation and hormone expression.
Methods: Heterozygous Igf2Flox males were mated with homozygous TpbpaCre female mice to generate litters of mixed genotype; 50:50 wildtype and Jz-Igf2UE. Fetal and placental weights were recorded on day 16 of pregnancy (term ˜day 20.5), when the Jz is at its largest. Placentas were bisected. One half was fixed in paraformaldehyde for histological assessment. The Jz of the other half was isolated and snap frozen for qPCR analysis of Igf2, Igf2 receptors, hormones and endocrine cell markers. Fetuses were sexed by Sry genotyping. Significant genotypic differences were assessed by t-test (P<0.05).
Results: Fetal and placental weights were unaltered with Jz-Igf2UE. However, Jz volumes of spongiotrophoblasts and glycogen cells were decreased in females with unaltered placental glycogen concentrations in both sexes. In both sexes, Jz-Igf2UE reduced Jz Igf2 expression and increased the steroidogenic gene, Cyp17a1. In females, Jz-Igf2UE increased insulin receptor α (Insra) and Tpbpa, but decreased insulin receptor β (Insrb) and placental lactogen 2 (Prl3b1). In males, Jz-Igf2UE decreased the type 2 IGF receptor (Igf2r) and trended to reduce the glycogen cell marker (Gjb3; P=0.07).
Conclusions: Jz-Igf2UE alters the cellular composition and hormone expression of the placental Jz. However, the nature of these changes were dependent on fetal sex. Despite changes in placental endocrine phenotype with Jz-Igf2UE, fetal and placental weights were unchanged in a mixed litter.