Igf2 deletion alters mouse placenta endocrine capacity in a sexually dimorphic manner

in Journal of Endocrinology
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  • 1 Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK

Correspondence should be addressed to A N Sferruzzi-Perri: ans48@cam.ac.uk
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The placenta regulates materno-fetal nutrient transfer and secretes hormones that enable maternal physiological support of the pregnancy. In mice, these functions are performed by the labyrinth (Lz) and junctional (Jz) zones, respectively. Insulin-like growth factor 2 (Igf2) is an imprinted gene expressed by the conceptus that is important for promoting fetal growth and placenta formation. However, the specific role of Igf2 in the Jz in regulating placental endocrine function and fetal development is unknown. This study used a novel model to investigate the effect of conditional loss of Igf2 in the Jz (Jz-Igf2UE) on placental endocrine cell formation and the expression of hormones and IGF signaling components in placentas from female and male fetuses. Jz-Igf2UE altered gross placental structure and expression of key endocrine and signaling genes in a sexually dimorphic manner. The volumes of spongiotrophoblast and glycogen trophoblast in the Jz were decreased in placentas from female but not male fetuses. Expression of insulin receptor was increased and expression of the MAPK pathway genes (Mek1, P38α) decreased in the placental Jz of female but not male fetuses. In contrast, expression of the type-1 and -2 IGF receptors and the MAPK pathway genes (H-ras, N-ras, K-ras) was decreased in the placental Jz from male but not female fetuses. Expression of the steroidogenic gene, Cyp17a1, was increased and placental lactogen-2 was decreased in the placenta of both sexes. In summary, we report that Jz-Igf2UE alters the cellular composition, IGF signaling components and hormone expression of the placental Jz in a manner largely dependent on fetal sex.

Supplementary Materials

    • Supplementary Table 1. QPCR primers and references where available for those published previously
    • Supplementary Fig. 1. Negative controls for in situ hybridization and immunohistochemistry experiments in mouse placentas. (A & B) Sense in situ hybridization probes for (A) Igf2 and (B) Prl8a8. (C) Secondary antibody only control used in immunohistochemistry experiments for (C) cleaved caspase-3. Black boxes represent the area magnified in the image below. Black bar represents 1 mm. Red bar represents 100 μm.
    • Supplementary Fig. 2. Jz-Igf2UE led to no alteration in the levels of cleaved caspase-3 in D16 mouse placentas. Immunostaining in (A) males and (B) females and the number of cleaved caspase-3 positive cells in the Jz of (C) male and (D) female placentas and in the Db of (E) male and (F) female placentas. The black scale bar represents 25 μm. Values presented as mean + SEM with n = 6 per sex and genotype across 6 litters. Spongiotrophoblast (SpT), glycogen cell (GC), trophoblast giant cell (TGC) and stroma (S).

 

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