Related Experiment Video
Updated: Apr 7, 2026
Mouse In Vivo Placental Targeted CRISPR Manipulation
Published on: April 14, 2023
Is Placental Mitochondrial Function a Regulator that Matches Fetal and Placental Growth to Maternal Nutrient Intake
Marcos R Chiaratti1, Sajida Malik2, Alan Diot2
1Nuffield Department of Obstetrics and Gynaecology, The Women's Centre, University of Oxford, Oxford, OX3 9DU, United Kingdom; Departamento de Genética e Evolução, Universidade Federal de São Carlos Rod. Washington Luís, km 235, Jardim Guanabara, São Carlos, SP, CEP 13.565-905, Brazil.
Background:
Effective fetal growth requires adequate maternal nutrition coupled to active transport of nutrients across the placenta, which, in turn requires ATP. Epidemiological and experimental evidence has shown that impaired maternal nutrition in utero results in an adverse postnatal phenotype for the offspring. Placental mitochondrial function might link maternal food intake to fetal growth since impaired placental ATP production, in response to poor maternal nutrition, could be a pathway linking maternal food intake to reduced fetal growth.
Method:
We assessed the effects of maternal diet on placental water content, ATP levels and mitochondrial DNA (mtDNA) content in mice at embryonic (E) day 18 (E18). Females maintained on either low- (LPD) or normal- (NPD) protein diets were mated with NPD males.
Results:
Fetal dry weight and placental efficiency (embryo/placental fresh weight) were positively correlated (r = 0.53, P = 0.0001). Individual placental dry weight was reduced by LPD (P = 0.003), as was the expression of amino acid transporter Slc38a2 and of growth factor Igf2. Placental water content, which is regulated by active transport of solutes, was increased by LPD (P = 0.0001). However, placental ATP content was also increased (P = 0.03). To investigate the possibility of an underlying mitochondrial stress response, we studied cultured human trophoblast cells (BeWos). High throughput imaging showed that amino acid starvation induces changes in mitochondrial morphology that suggest stress-induced mitochondrial hyperfusion. This is a defensive response, believed to increase mitochondrial efficiency, that could underlie the increase in ATP observed in placenta.
Conclusions:
These findings reinforce the pathophysiological links between maternal diet and conceptus mitochondria, potentially contributing to metabolic programming. The quiet embryo hypothesis proposes that pre-implantation embryo survival is best served by a relatively low level of metabolism. This may extend to post-implantation trophoblast responses to nutrition.
