High fat diet-induced maternal obesity alters fetal hippocampal development.
The importance of maternal nutrition for fetal brain development is increasingly recognized. Previous studies have suggested that maternal obesity or maternal exposure to obesogenic diets may permanently alter brain structure and function in the offspring. To test whether maternal exposure to a high-fat diet, prior and during gestation, alters fetal hippocampal development, we fed 8-week old C57BL/6 females with a high-fat diet (60% calories from fat) for 10 weeks prior to matting and 17 days after. Fetal brains at embryonic day E17 were used to determine developmental changes in the hippocampus. We report that maternal exposure to the high-fat diet induced small for gestational age (SGA) status and fetal resorption. The proliferation of neural progenitors was increased in the neuroepithelium from hippocampus and cortex in fetuses from mothers fed the high-fat diet when compared to controls, but decreased within the dentate gyrus (DG). Apoptosis in the hippocampus was decreased (Ammon's Horn and fimbria). The differentiation of calretinin-positive neurons within the DG was also decreased. These data indicate that, under the influence of a maternal high-fat diet administered prior and during gestation, fetal hippocampal development is altered at embryonic day 17, as indicated by region-specific changes in proliferation of neural precursors, decreased apoptosis, and by decreased neuronal differentiation within the dentate gyrus.
Niculescu
Mihai D
MD
Nutrition Research Institute, University of North Carolina, Chapel Hill, NC, United States. mihai_niculescu@unc.edu
Lupu
Daniel S
DS
D000818:Animals; D001835:Body Weight; D064032:Calbindin 2; D049109:Cell Proliferation; D004032:Diet; D004041:Dietary Fats / Q000009:adverse effects*; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009765:Obesity / Q000150:complications*; D011247:Pregnancy; D011897:Random Allocation; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
C576511:Calb2 protein, mouse; D064032:Calbindin 2; D004041:Dietary Fats; D064030:S100 Calcium Binding Protein G
JAMA. 2009 Feb 11;301(6):636-50
19211471
J Nutr. 1998 Dec;128(12):2505-11
9868200
FASEB J. 2006 Jan;20(1):43-9
16394266
BJOG. 2008 Nov;115(12):1529-37
19035989
Eur J Pharmacol. 2008 May 6;585(1):163-75
18423446
CNS Neurol Disord Drug Targets. 2006 Oct;5(5):531-46
17073656
Neuroscience. 2009 May 5;160(2):295-306
19217934
Prev Med. 1998 Mar-Apr;27(2):189-94
9578993
Exp Biol Med (Maywood). 2003 Feb;228(2):152-9
12563021
Acta Obstet Gynecol Scand. 2004 Sep;83(9):801-7
15315590
J Neurosci. 2000 Aug 15;20(16):6095-105
10934259
Am J Obstet Gynecol. 2009 Apr;200(4):395.e1-9
19200933
Am J Clin Nutr. 1990 Sep;52(3):426-30
2393005
Development. 1996 Apr;122(4):1165-74
8620843
N Engl J Med. 1998 Jan 15;338(3):147-52
9428815
Behav Brain Res. 2007 Aug 22;182(1):57-66
17590450
J Neural Transm (Vienna). 2003 Jan;110(1):95-110
12541015
FASEB J. 2009 Jun;23(6):1920-34
19158155
J Neurosci. 2008 Nov 12;28(46):12107-19
19005075
J Nutr Health Aging. 2000;4(4):202-7
11115801
Mol Cell Neurosci. 2003 Nov;24(3):603-13
14664811
Ann N Y Acad Sci. 2008 Nov;1144:189-202
19076377
Physiol Res. 2008;57(5):727-734
17949248
Curr Med Chem. 2006;13(18):2127-38
16918343
Horm Metab Res. 2007 Jul;39(7):489-94
17611900
Hypertension. 2008 Feb;51(2):383-92
18086952
Neuroreport. 1997 Nov 10;8(16):3625-9
9427338
FEBS J. 2007 Aug;274(15):3855-63
17617229
J Mol Neurosci. 2000 Oct;15(2):99-108
11220789
Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E356-67
18492779
J Exp Biol. 2007 Jan;210(Pt 1):65-74
17170149
Brain Dev. 1997 Apr;19(3):165-70
9134186
Ann Intern Med. 2003 Sep 2;139(5 Pt 2):441-4
12965973
FASEB J. 2009 Jan;23(1):271-8
18827021
J Clin Endocrinol Metab. 2006 Sep;91(9):3548-52
16787984
Eur J Neurol. 2006 Dec;13(12):1385-8
17116226
Appetite. 2007 Nov;49(3):675-8
17543417
J Comp Neurol. 1979 Jun 1;185(3):423-59
86549
Dev Med Child Neurol. 1980 Aug;22(4):525-45
7409345
Teratology. 1977 Oct;16(2):235-46
73229
Chromosoma. 1997 Nov;106(6):348-60
9362543
J Comp Neurol. 1990 Nov 15;301(3):325-42
2262594
Behav Brain Res. 2006 Dec 15;175(2):374-82
17081630
Trends Neurosci. 2003 Mar;26(3):137-46
12591216
Rev Endocr Metab Disord. 2007 Jun;8(2):85-94
17638083
Neuroscience. 2002;112(4):803-14
12088740
J Comp Neurol. 1990 Nov 15;301(3):365-81
2262596
J Comp Neurol. 1994 Apr 22;342(4):571-95
7913715
Peptides. 2006 Nov;27(11):2738-49
16914228