PMID- 29614340
OWN - NLM
STAT- MEDLINE
DCOM- 20190508
LR  - 20190508
IS  - 1872-8057 (Electronic)
IS  - 0303-7207 (Linking)
VI  - 474
DP  - 2018 Oct 15
TI  - Maternal lipopolysaccharide exposure results in glucose metabolism disorders and 
      sex hormone imbalance in male offspring.
PG  - 272-283
LID - S0303-7207(18)30119-9 [pii]
LID - 10.1016/j.mce.2018.03.019 [doi]
AB  - An adverse intrauterine environment may be an important factor contributing to 
      the development of type 2 diabetes in later life. The present study investigated 
      the longitudinal effects of maternal lipopolysaccharide (LPS) exposure during the 
      third trimester on glucose metabolism and sex hormone balance in the offspring. 
      Pregnant mice were intraperitoneally injected with LPS (50 mug/kg) daily from 
      gestational day (GD) 15 to GD17. Glucose tolerance test (GTT) and insulin 
      tolerance test (ITT) were assessed at postnatal day (PND) 60 and PND120. Sex 
      hormones, their receptors, and metabolic enzymes (aromatase) were measured in 
      male offspring at different phases of development (PND14: juvenile; PND35: 
      adolescence; PND60: adulthood; and PND120: middle age). LPS-exposed male 
      offspring exhibited glucose intolerance and insulin resistance by GTT and ITT at 
      middle age, accompanied by an increase in fasting blood glucose and reductions in 
      serum insulin levels and hepatic phosphorylated (p) -AKT/AKT ratio. However, 
      glucose intolerance and insulin resistance were not observed in LPS-exposed 
      female offspring. Maternal LPS exposure upregulated hepatic aromatase proteins 
      and mRNA levels in male offspring at all time points. At adolescence, the 
      testosterone/estradiol ratio (T/E2) was markedly reduced in LPS-exposed male 
      offspring. Moreover, maternal LPS exposure significantly increased hepatic 
      estrogen receptor (ER) alpha expressions and decreased hepatic androgen receptor (AR) 
      expressions in male offspring. At adulthood, maternal LPS exposure increased 
      serum estradiol levels, decreased serum testosterone levels and elevated hepatic 
      ERbeta expressions in male offspring. In conclusion, maternal LPS exposure 
      upregulated aromatase expressions, followed by a reduction in the T/E2 ratio and 
      an alteration in sex hormone receptor activity, which might be involved in the 
      development of glucose metabolism disorders in middle-aged male offspring. This 
      study provides a novel clue and direction to clarify the pathogenesis of maternal 
      infection-related diabetes in male offspring.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Zhao, Mei
AU  - Zhao M
AD  - School of Nursing, Anhui Medical University, Hefei 230032, China; Anhui 
      Provincial Key Laboratory of Population Health & Aristogenics, Hefei, 230032, 
      China. Electronic address: zhaomei@ahmu.edu.cn.
FAU - Yuan, Li
AU  - Yuan L
AD  - School of Nursing, Anhui Medical University, Hefei 230032, China.
FAU - Yuan, Man-Man
AU  - Yuan MM
AD  - School of Nursing, Anhui Medical University, Hefei 230032, China.
FAU - Huang, Li-Li
AU  - Huang LL
AD  - School of Nursing, Anhui Medical University, Hefei 230032, China.
FAU - Su, Chang
AU  - Su C
AD  - The Fourth Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
FAU - Chen, Yuan-Hua
AU  - Chen YH
AD  - Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, 
      230032, China; Department of Histology and Embryology, Anhui Medical University, 
      Hefei, 230032, China.
FAU - Yang, Yu-Ying
AU  - Yang YY
AD  - School of Nursing, Anhui Medical University, Hefei 230032, China.
FAU - Hu, Yan
AU  - Hu Y
AD  - School of Nursing, Anhui Medical University, Hefei 230032, China.
FAU - Xu, De-Xiang
AU  - Xu DX
AD  - Anhui Provincial Key Laboratory of Population Health & Aristogenics, Hefei, 
      230032, China; Department of Toxicology, Anhui Medical University, Hefei, 230032, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180401
PL  - Ireland
TA  - Mol Cell Endocrinol
JT  - Molecular and cellular endocrinology
JID - 7500844
RN  - 0 (Gonadal Steroid Hormones)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, Cell Surface)
RN  - EC 1.14.14.1 (Aromatase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Aromatase/metabolism
MH  - Body Weight/drug effects
MH  - Female
MH  - Glucose/*metabolism
MH  - Gonadal Steroid Hormones/blood/*metabolism
MH  - Insulin Resistance
MH  - Lipid Metabolism/drug effects
MH  - Lipopolysaccharides/*toxicity
MH  - Liver/drug effects/metabolism
MH  - Male
MH  - *Maternal Exposure
MH  - Mice, Inbred ICR
MH  - Phosphorylation/drug effects
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/blood/*pathology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptors, Cell Surface/metabolism
OTO - NOTNLM
OT  - Aromatase
OT  - Diabetes
OT  - Insulin resistance
OT  - Lipopolysaccharide
OT  - Pregnancy
OT  - Sex hormone
EDAT- 2018/04/04 06:00
MHDA- 2019/05/09 06:00
CRDT- 2018/04/04 06:00
PHST- 2017/10/05 00:00 [received]
PHST- 2018/03/16 00:00 [revised]
PHST- 2018/03/31 00:00 [accepted]
PHST- 2018/04/04 06:00 [pubmed]
PHST- 2019/05/09 06:00 [medline]
PHST- 2018/04/04 06:00 [entrez]
AID - S0303-7207(18)30119-9 [pii]
AID - 10.1016/j.mce.2018.03.019 [doi]
PST - ppublish
SO  - Mol Cell Endocrinol. 2018 Oct 15;474:272-283. doi: 10.1016/j.mce.2018.03.019. 
      Epub 2018 Apr 1.