Chorionic somatomammotropin impacts early fetal growth and placental gene expression

in Journal of Endocrinology
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Several developmental windows, including placentation, must be negotiated to establish and maintain pregnancy. Impaired placental function can lead to preeclampsia and/or intrauterine growth restriction (IUGR), resulting in increased infant mortality and morbidity. It has been hypothesized that chorionic somatomammotropin (CSH) plays a significant role in fetal development, potentially by modifying maternal and fetal metabolism. Recently, using lentiviral-mediated in vivo RNA interference in sheep, we demonstrated significant reductions in near-term (135 days of gestation; dGA) fetal and placental size, and altered fetal liver gene expression, resulting from CSH deficiency. We sought to examine the impact of CSH deficiency on fetal and placental size earlier in gestation (50 dGA), and to examine placental gene expression at 50 and 135 dGA. At 50 dGA, CSH-deficient pregnancies exhibited a 41% reduction (P ≤ 0.05) in uterine vein concentrations of CSH, and significant (P ≤ 0.05) reductions (≈21%) in both fetal body and liver weights. Placentae harvested at 50 and 135 dGA exhibited reductions in IGF1 and IGF2 mRNA concentrations, along with reductions in SLC2A1 and SLC2A3 mRNA. By contrast, mRNA concentrations for various members of the System A, System L and System y+ amino acid transporter families were not significantly impacted. The IUGR observed at the end of the first-third of gestation indicates that the near-term IUGR reported previously, began early in gestation, and may have in part resulted from deficits in the paracrine action of CSH within the placenta. These results provide further compelling evidence for the importance of CSH in the progression and outcome of pregnancy.

 

      Society for Endocrinology

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    (A) Uterine vein CSH concentration at 50 dGA. (B) Placental CSH mRNA concentrations at 50 dGA. (C) Placental CSH concentrations at 50 dGA. *P ≤ 0.05 when CSH-deficient pregnancies are compared with controls.

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    (A) Effect of CSH deficiency on SLC2A1 mRNA concentrations in the placenta at 50 and 135 dGA. (B) Effect of CSH deficiency on SLC2A1 concentrations in the placenta at 50 and 135 dGA. *P ≤ 0.05 when CSH-deficient pregnancies are compared with controls, within a gestational age.

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    (A) Effect of CSH deficiency on SLC2A3 mRNA concentrations in the placenta at 50 and 135 dGA. (B) Effect of CSH deficiency on SLC2A3 concentrations in the placenta at 50 and 135 dGA. *P ≤ 0.05 when CSH-deficient pregnancies are compared with controls, within a gestational age.

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    Effect of CSH deficiency on SLC2A8 mRNA concentrations in the placenta at 50 and 135 dGA. *P ≤ 0.05 when CSH-deficient pregnancies are compared with controls, within a gestational age.

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    (A) Effect of CSH deficiency on amino acid transporter mRNA concentrations in the placenta at 50 dGA. (B) Effect of CSH deficiency on amino acid transporter mRNA concentrations in the placenta at 135 dGA. P ≤ 0.10 when CSH-deficient pregnancies are compared with controls, within a gestational age.

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