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Is Placental Mitochondrial Function a Regulator that Matches Fetal and Placental Growth to Maternal Nutrient Intake in the Mouse?

Chiaratti MR, Malik S, Diot A, Rapa E, Macleod L, Morten K, Vatish M, Boyd R, Poulton J - PLoS ONE (2015)

Bottom Line: 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.The quiet embryo hypothesis proposes that pre-implantation embryo survival is best served by a relatively low level of metabolism.

View Article: PubMed Central - PubMed

Affiliation: Nuffield 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.

ABSTRACT

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: 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.

No MeSH data available.


Related in: MedlinePlus

Placental ATP increases with fetal water content in mice and is inversely correlated to placenta efficiency (fetal/placental fresh weight).The content of ATP was measured in day18 (pregnancy) mouse placentas from mothers subjected to normal (NPD) or low (LPD) protein diets. Each dot is representative of a single placenta. In (A), the line represents the correlation between the two variables for NPD (r = 0.81, P = 0.0001) and LPD (r = 0.60, P = 0.025). In (B), the two variables were inversely correlated (r = -0.56, P = 0.0001). In (C), values are reported as means ± SEM and difference (P = 0.03) between groups is indicated by (*). The number of samples considered in (C) was 45 for the NPD and 34 for the LPD.
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pone.0130631.g003: Placental ATP increases with fetal water content in mice and is inversely correlated to placenta efficiency (fetal/placental fresh weight).The content of ATP was measured in day18 (pregnancy) mouse placentas from mothers subjected to normal (NPD) or low (LPD) protein diets. Each dot is representative of a single placenta. In (A), the line represents the correlation between the two variables for NPD (r = 0.81, P = 0.0001) and LPD (r = 0.60, P = 0.025). In (B), the two variables were inversely correlated (r = -0.56, P = 0.0001). In (C), values are reported as means ± SEM and difference (P = 0.03) between groups is indicated by (*). The number of samples considered in (C) was 45 for the NPD and 34 for the LPD.

Mentions: To investigate whether ATP and mtDNA content are linked as we predicted, we measured ATP and mtDNA (relative to nuclear DNA) levels in mouse placentas. Placental ATP content was not reduced in fetuses with a high water content (Fig 3A), but was inversely proportional (r = -0.56, P = 0.0001) to placental efficiency (Fig 3B). Furthermore, the placental ATP level was increased (P = 0.03) by the LPD (6.8 ± 0.453 mmol) compared with the NPD (5.7 ± 0.198 mmol; Fig 3C). Yet, placental mtDNA content (measured as the ratio of mtDNA to nuclear DNA) was not significantly increased (P = 0.82) in LPD (1.07 ± 0.089) compared to NPD (1.0 ± 0.087) placenta. Neither did total placental ATP and total mtDNA content correlate (not shown). Because we had previously found that mtDNA content varied by 3–4 fold within regions of a single placenta [24], we re-visited these data by dividing each placenta into five portions (each weighing 10–20 mg). In this case (Fig 4), a significant positive relationship between placental mtDNA/nuclear DNA and ATP became apparent (r = 0.34, P = 0.01) whereas mtDNA varied by 1.5–4 fold within several pieces of a single placenta. Furthermore, in both runs litter placental mtDNA content was inversely correlated to summed litter fresh weight (r = -0.59, P = 0.04; Fig 5A), summed litter placental fresh weight (r = -0.68, P = 0.02; Fig 5B) and litter size (r = -0.68, P = 0.01; Fig 5C).


Is Placental Mitochondrial Function a Regulator that Matches Fetal and Placental Growth to Maternal Nutrient Intake in the Mouse?

Chiaratti MR, Malik S, Diot A, Rapa E, Macleod L, Morten K, Vatish M, Boyd R, Poulton J - PLoS ONE (2015)

Placental ATP increases with fetal water content in mice and is inversely correlated to placenta efficiency (fetal/placental fresh weight).The content of ATP was measured in day18 (pregnancy) mouse placentas from mothers subjected to normal (NPD) or low (LPD) protein diets. Each dot is representative of a single placenta. In (A), the line represents the correlation between the two variables for NPD (r = 0.81, P = 0.0001) and LPD (r = 0.60, P = 0.025). In (B), the two variables were inversely correlated (r = -0.56, P = 0.0001). In (C), values are reported as means ± SEM and difference (P = 0.03) between groups is indicated by (*). The number of samples considered in (C) was 45 for the NPD and 34 for the LPD.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488591&req=5

pone.0130631.g003: Placental ATP increases with fetal water content in mice and is inversely correlated to placenta efficiency (fetal/placental fresh weight).The content of ATP was measured in day18 (pregnancy) mouse placentas from mothers subjected to normal (NPD) or low (LPD) protein diets. Each dot is representative of a single placenta. In (A), the line represents the correlation between the two variables for NPD (r = 0.81, P = 0.0001) and LPD (r = 0.60, P = 0.025). In (B), the two variables were inversely correlated (r = -0.56, P = 0.0001). In (C), values are reported as means ± SEM and difference (P = 0.03) between groups is indicated by (*). The number of samples considered in (C) was 45 for the NPD and 34 for the LPD.
Mentions: To investigate whether ATP and mtDNA content are linked as we predicted, we measured ATP and mtDNA (relative to nuclear DNA) levels in mouse placentas. Placental ATP content was not reduced in fetuses with a high water content (Fig 3A), but was inversely proportional (r = -0.56, P = 0.0001) to placental efficiency (Fig 3B). Furthermore, the placental ATP level was increased (P = 0.03) by the LPD (6.8 ± 0.453 mmol) compared with the NPD (5.7 ± 0.198 mmol; Fig 3C). Yet, placental mtDNA content (measured as the ratio of mtDNA to nuclear DNA) was not significantly increased (P = 0.82) in LPD (1.07 ± 0.089) compared to NPD (1.0 ± 0.087) placenta. Neither did total placental ATP and total mtDNA content correlate (not shown). Because we had previously found that mtDNA content varied by 3–4 fold within regions of a single placenta [24], we re-visited these data by dividing each placenta into five portions (each weighing 10–20 mg). In this case (Fig 4), a significant positive relationship between placental mtDNA/nuclear DNA and ATP became apparent (r = 0.34, P = 0.01) whereas mtDNA varied by 1.5–4 fold within several pieces of a single placenta. Furthermore, in both runs litter placental mtDNA content was inversely correlated to summed litter fresh weight (r = -0.59, P = 0.04; Fig 5A), summed litter placental fresh weight (r = -0.68, P = 0.02; Fig 5B) and litter size (r = -0.68, P = 0.01; Fig 5C).

Bottom Line: 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.The quiet embryo hypothesis proposes that pre-implantation embryo survival is best served by a relatively low level of metabolism.

View Article: PubMed Central - PubMed

Affiliation: Nuffield 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.

ABSTRACT

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: 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.

No MeSH data available.


Related in: MedlinePlus