title: Expression of the placental transcriptome in maternal nutrient reduction in baboons is dependent on fetal sex.
abstract: Maternal undernutrition increases the risk of perinatal complications and predisposes offspring to obesity, diabetes, and cardiovascular disease later in life. Emerging evidence suggests that changes in placental function play a role in linking altered maternal nutrition in pregnancy to the subsequent development of adult disease. The susceptibility for disease in response to an adverse intrauterine environment differs distinctly between boys and girls, with girls typically having better outcomes. Here, we tested the hypothesis that regulation of the placental transcriptome by maternal nutrient reduction (NR) is dependent on fetal sex. We used a nonhuman primate model of NR in which maternal global food intake was reduced by 30% in baboons starting at gestational day (GD) 30. At GD 165 (term = GD 183), placental genome expression profiling of 6 control (n = 3 females, 3 males) and 6 nutrient restricted (n = 3 females, 3 males) fetuses was carried out followed by bioinformatic analysis. Surprisingly, there was no coordinated placental molecular response to decreased nutrient availability when analyzing the data without accounting for fetal sex. In contrast, female placentas exhibited a highly coordinated response that included upregulation of genes in networks, pathways, and functional groups related to programmed cell death and downregulation of genes in networks, pathways, and functional groups associated with cell proliferation. These changes were not apparent in the male placentas. Our data support the concept that female placentas initiate complex adaptive responses to an adverse intrauterine environment, which may contribute to increased survival and better pregnancy outcomes in girls.
authors.affiliation: Department of Genetics.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Cox
authors.forename: Cun
authors.initials: C
authors.lastname: Li
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Glenn
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lange
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Spradling
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nathanielsz
authors.forename: Thomas
authors.initials: T
authors.lastname: Jansson
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D010215:Papio / Q000196:embryology* / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D015203:Reproducibility of Results; D012737:Sex Factors; D059467:Transcriptome; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D051028:bcl-2-Associated X Protein; D053148:Caspase 3
references.citation: Ginekol Pol. 2009 Sep;80(9):652-6
references.pmid: 19886237
references.citation: J Cell Mol Med. 2012 Sep;16(9):2060-73
references.pmid: 22128816
references.citation: J Clin Endocrinol Metab. 2001 Oct;86(10):5017-24
references.pmid: 11600579
references.citation: Genome Biol. 2003;4(1):R7
references.pmid: 12540299
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Aug;297(2):R510-4
references.pmid: 19535674
references.citation: Endocrinology. 2010 Oct;151(10):4969-81
references.pmid: 20810566
references.citation: J Reprod Immunol. 2011 Jun;90(1):41-9
references.pmid: 21704384
references.citation: Early Hum Dev. 2004 Jan;76(1):47-54
references.pmid: 14729162
references.citation: J Immunol. 2009 Feb 1;182(3):1411-20
references.pmid: 19155488
references.citation: Br Med J. 1980 Nov 8;281(6250):1253
references.pmid: 7427655
references.citation: J Biol Chem. 2006 Jan 6;281(1):559-68
references.pmid: 16267050
references.citation: Br J Obstet Gynaecol. 1995 Oct;102(10):818-25
references.pmid: 7547740
references.citation: Reprod Biol Endocrinol. 2011 Aug 02;9:107
references.pmid: 21810232
references.citation: Placenta. 2011 May;32(5):395-9
references.pmid: 21435715
references.citation: Placenta. 2010 Mar;31 Suppl:S54-9
references.pmid: 20149453
references.citation: Placenta. 2012 Feb;33 Suppl:S37-41
references.pmid: 22118870
references.citation: J Microsc. 1997 May;186(Pt 2):153-63
references.pmid: 9183852
references.citation: Arch Dis Child Fetal Neonatal Ed. 2000 Nov;83(3):F182-5
references.pmid: 11040165
references.citation: Pediatrics. 1981 May;67(5):614-7
references.pmid: 7254990
references.citation: Aust N Z J Obstet Gynaecol. 2008 Aug;48(4):375-83
references.pmid: 18837843
references.citation: J Med Primatol. 2004 Jun;33(3):117-26
references.pmid: 15102068
references.citation: Maturitas. 2011 Oct;70(2):141-5
references.pmid: 21802226
references.citation: Cancer Cell. 2003 Nov;4(5):371-81
references.pmid: 14667504
references.citation: Nat Genet. 2000 May;25(1):25-9
references.pmid: 10802651
references.citation: Clin Sci (Lond). 2007 Jul;113(1):1-13
references.pmid: 17536998
references.citation: Placenta. 2011 Jun;32(6):454-61
references.pmid: 21453968
references.citation: Placenta. 2007 Aug-Sep;28(8-9):783-93
references.pmid: 17382997
references.citation: Biol Reprod. 2011 Jun;84(6):1077-86
references.pmid: 21270431
references.citation: Environ Health Perspect. 2000 Jun;108 Suppl 3:545-53
references.pmid: 10852853
references.citation: Am J Obstet Gynecol. 2009 May;200(5):532.e1-8
references.pmid: 19285652
references.citation: Mol Cell. 1999 Oct;4(4):585-95
references.pmid: 10549290
references.citation: PLoS One. 2009 Nov 30;4(11):e8055
references.pmid: 19956639
references.citation: Horm Res. 2005;64 Suppl 3:2-7
references.pmid: 16439838
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 23;107(12):5557-62
references.pmid: 20212133
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5478-83
references.pmid: 16567644
references.citation: Placenta. 2010 Mar;31 Suppl:S33-9
references.pmid: 20004469
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Dec;295(6):R1941-52
references.pmid: 18971349
references.citation: Am J Obstet Gynecol. 2010 Oct;203(4):364.e13-8
references.pmid: 20599184
references.citation: Gend Med. 2007 Mar;4(1):19-30
references.pmid: 17584623
references.citation: J Med Primatol. 2008 Jun;37(3):154-61
references.pmid: 18547259
references.citation: Science. 2004 Sep 17;305(5691):1733-6
references.pmid: 15375258
references.citation: Placenta. 2007 Nov-Dec;28(11-12):1200-10
references.pmid: 17707905
references.citation: Cell Death Differ. 1998 Aug;5(8):646-52
references.pmid: 10200519
references.citation: Placenta. 2011 Aug;32(8):570-8
references.pmid: 21641640
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D277-80
references.pmid: 14681412
references.citation: J Comput Biol. 2000;7(6):819-37
references.pmid: 11382364
references.citation: J Physiol. 2006 Apr 1;572(Pt 1):67-85
references.pmid: 16513668
references.citation: Placenta. 2002 Apr;23 Suppl A:S20-7
references.pmid: 11978056