ESPEYB21 14. The Year in Science and Medicine Basic Biology and Molecular Mechanisms (5 abstracts)
14.4. Fetal manipulation of maternal metabolism is a critical function of the imprinted Igf2 gene
Lopez-Tello J , Yong HEJ , Sandovici I , Dowsett GKC , Christoforou ER , Salazar-Petres E , Boyland R , Napso T , Yeo GSH , Lam BYH , Constancia M & Sferruzzi-Perri AN.
Cell Metab. 2023 Jul 11;35(7):1195–1208.e6. doi: 10.1016/j.cmet.2023.06.007
Brief Summary:This study in mice shows that insulin-like growth factor 2 (IGF2), encoded by an imprinted gene and expressed by placental endocrine cells, is essential for the adaptive changes in maternal glucose and lipid metabolism during pregnancy to promote fetal growth. Failure of this adaptive program during pregnancy also resulted in metabolic dysfunction of offspring mice later in their life.
IGF2 has been longer known to be involved in the regulation of fetal growth, but its exact mechanism of action was unclear. The imprinted gene Igf2 is highly expressed in (murine) placental cells. This study shows that Igf2 controls placental hormone production (e.g. prolactins) and establishes pregnancy-related insulin resistance to re-allocate nutrients to the fetus. The researchers also show that lack of placental Igf2 causes growth restriction and hypoglycemia in the fetus and also has long-lasting metabolic consequences reaching beyond fetal life. It illustrates how the fetus manipulates the metabolism of the mother to receive enough glucose.
Understanding how fetal factors like IGF2 affect maternal metabolism may help to better comprehend conditions such as gestational diabetes or preeclampsia, potentially leading to improved strategies for managing these pregnancy complications.
This study showing how the fetus and mother interact to regulate the glucose/insulin metabolism between them in pregnancy, was summarized in a ‘Research Highlight’ in (1) illustrating the importance of this novel mechanistic finding.
Reference: 1. Fetal orchestration of maternal metabolism via IGF2. Nat Rev Endocrinol. 2023 Oct;19(10):557; doi: 10.1038/s41574-023-00884-7.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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