Sex‐specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring

Obesity during pregnancy has been shown to increase the risk of metabolic diseases in the offspring. However, the factors within the maternal milieu which affect offspring phenotypes and the underlying mechanisms remain unknown. The adipocyte hormone leptin plays a key role in regulating energy home...

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Main Authors: Elena I. Denisova, Valeria V. Kozhevnikova, Nadezhda M. Bazhan, Elena N. Makarova
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:FEBS Open Bio
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Online Access:https://doi.org/10.1002/2211-5463.12757
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author Elena I. Denisova
Valeria V. Kozhevnikova
Nadezhda M. Bazhan
Elena N. Makarova
author_facet Elena I. Denisova
Valeria V. Kozhevnikova
Nadezhda M. Bazhan
Elena N. Makarova
author_sort Elena I. Denisova
collection DOAJ
description Obesity during pregnancy has been shown to increase the risk of metabolic diseases in the offspring. However, the factors within the maternal milieu which affect offspring phenotypes and the underlying mechanisms remain unknown. The adipocyte hormone leptin plays a key role in regulating energy homeostasis and is known to participate in sex‐specific developmental programming. To examine the action of leptin on fetal growth, placental gene expression and postnatal offspring metabolism, we injected C57BL mice with leptin or saline on gestational day 12 and then measured body weights (BWs) of offspring fed on a standard or obesogenic diet, as well as mRNA expression levels of insulin‐like growth factors and glucose and amino acid transporters. Male and female offspring born to leptin‐treated mothers exhibited growth retardation before and a growth surge after weaning. Mature male offspring, but not female offspring, exhibited increased BWs on a standard diet. Leptin administration prevented the development of hyperglycaemia in the obese offspring of both sexes. The placentas of the male and female foetuses differed in size and gene expression, and leptin injection decreased the fetal weights of both sexes, the placental weights of the male foetuses and placental gene expression of the GLUT1 glucose transporter in female foetuses. The data suggest that mid‐pregnancy is an ontogenetic window for the sex‐specific programming effects of leptin, and these effects may be exerted via fetal sex‐specific placental responses to leptin administration.
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spelling doaj-art-0f1ac42682b44f12bb27afce35fe6eec2024-12-09T14:15:33ZengWileyFEBS Open Bio2211-54632020-01-011019610610.1002/2211-5463.12757Sex‐specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspringElena I. Denisova0Valeria V. Kozhevnikova1Nadezhda M. Bazhan2Elena N. Makarova3Laboratory of Physiological Genetics Institute of Cytology and Genetics the Siberian Branch of the Russian Academy of Sciences Novosibirsk RussiaLaboratory of Physiological Genetics Institute of Cytology and Genetics the Siberian Branch of the Russian Academy of Sciences Novosibirsk RussiaLaboratory of Physiological Genetics Institute of Cytology and Genetics the Siberian Branch of the Russian Academy of Sciences Novosibirsk RussiaLaboratory of Physiological Genetics Institute of Cytology and Genetics the Siberian Branch of the Russian Academy of Sciences Novosibirsk RussiaObesity during pregnancy has been shown to increase the risk of metabolic diseases in the offspring. However, the factors within the maternal milieu which affect offspring phenotypes and the underlying mechanisms remain unknown. The adipocyte hormone leptin plays a key role in regulating energy homeostasis and is known to participate in sex‐specific developmental programming. To examine the action of leptin on fetal growth, placental gene expression and postnatal offspring metabolism, we injected C57BL mice with leptin or saline on gestational day 12 and then measured body weights (BWs) of offspring fed on a standard or obesogenic diet, as well as mRNA expression levels of insulin‐like growth factors and glucose and amino acid transporters. Male and female offspring born to leptin‐treated mothers exhibited growth retardation before and a growth surge after weaning. Mature male offspring, but not female offspring, exhibited increased BWs on a standard diet. Leptin administration prevented the development of hyperglycaemia in the obese offspring of both sexes. The placentas of the male and female foetuses differed in size and gene expression, and leptin injection decreased the fetal weights of both sexes, the placental weights of the male foetuses and placental gene expression of the GLUT1 glucose transporter in female foetuses. The data suggest that mid‐pregnancy is an ontogenetic window for the sex‐specific programming effects of leptin, and these effects may be exerted via fetal sex‐specific placental responses to leptin administration.https://doi.org/10.1002/2211-5463.12757developmental programmingleptinmiceplacentapregnancy
spellingShingle Elena I. Denisova
Valeria V. Kozhevnikova
Nadezhda M. Bazhan
Elena N. Makarova
Sex‐specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring
FEBS Open Bio
developmental programming
leptin
mice
placenta
pregnancy
title Sex‐specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring
title_full Sex‐specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring
title_fullStr Sex‐specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring
title_full_unstemmed Sex‐specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring
title_short Sex‐specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring
title_sort sex specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring
topic developmental programming
leptin
mice
placenta
pregnancy
url https://doi.org/10.1002/2211-5463.12757
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AT nadezhdambazhan sexspecificeffectsofleptinadministrationtopregnantmiceontheplacentaeandthemetabolicphenotypesofoffspring
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