TY - JOUR

T1 - Sex-specific effects of leptin administration to pregnant mice on the placentae and the metabolic phenotypes of offspring

AU - Denisova, Elena I.

AU - Kozhevnikova, Valeria V.

AU - Bazhan, Nadezhda M.

AU - Makarova, Elena N.

N1 - © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

PY - 2019/11/25

Y1 - 2019/11/25

N2 - 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.

AB - 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.

KW - developmental programming

KW - leptin

KW - mice

KW - placenta

KW - pregnancy

KW - FETAL-GROWTH

KW - ADAPTATIONS

KW - RESTRICTION

KW - NUTRIENT TRANSPORT

KW - OBESITY

KW - ORIGINS

KW - DIET

KW - AMINO-ACIDS

KW - RESISTANCE

KW - WEIGHT

UR - http://www.scopus.com/inward/record.url?scp=85075471539&partnerID=8YFLogxK

U2 - 10.1002/2211-5463.12757

DO - 10.1002/2211-5463.12757

M3 - Article

C2 - 31703240

AN - SCOPUS:85075471539

VL - 10

SP - 96

EP - 106

JO - FEBS Open Bio

JF - FEBS Open Bio

SN - 2211-5463

IS - 1

ER -