title: Low female birth weight and advanced maternal age programme alterations in next-generation blastocyst development.
abstract: Low birth weight is associated with an increased risk for adult disease development with recent studies highlighting transmission to subsequent generations. However, the mechanisms and timing of programming of disease transmission to the next generation remain unknown. The aim of this study was to examine the effects of low birth weight and advanced maternal age on second-generation preimplantation blastocysts. Uteroplacental insufficiency or sham surgery was performed in late-gestation WKY pregnant rats, giving rise to first-generation (F1) restricted (born small) and control offspring respectively. F1 control and restricted females, at 4 or 12 months of age, were naturally mated with normal males. Second-generation (F2) blastocysts from restricted females displayed reduced expression of genes related to growth compared with F2 control (P<0.05). Following 24 h culture, F2 restricted blastocysts had accelerated development, with increased total cell number, a result of increased trophectoderm cells compared with control (P<0.05). There were alterations in carbohydrate and serine utilisation in F2 restricted blastocysts and F2 restricted outgrowths from 4-month-old females respectively (P<0.05). F2 blastocysts from aged restricted females were developmentally delayed at retrieval, with reduced total cell number attributable to reduced trophectoderm number with changes in carbohydrate utilisation (P<0.05). Advanced maternal age resulted in alterations in a number of amino acids in media obtained from F2 blastocyst outgrowths (P<0.05). These findings demonstrate that growth restriction and advanced maternal age can alter F2 preimplantation embryo physiology and the subsequent offspring growth.
authors: Department of PhysiologySchool of BioSciencesThe University of Melbourne, Parkville, Victoria 3010, AustraliaDepartment of Obstetrics and GynaecologyMercy Hospital, The University of Melbourne, Heidelberg, Victoria 3084, Australia.
authors: Jordanna S
authors: JS
authors: Master
authors: Department of PhysiologySchool of BioSciencesThe University of Melbourne, Parkville, Victoria 3010, AustraliaDepartment of Obstetrics and GynaecologyMercy Hospital, The University of Melbourne, Heidelberg, Victoria 3084, Australia.
authors: George A
authors: GA
authors: Thouas
authors: Department of PhysiologySchool of BioSciencesThe University of Melbourne, Parkville, Victoria 3010, AustraliaDepartment of Obstetrics and GynaecologyMercy Hospital, The University of Melbourne, Heidelberg, Victoria 3084, Australia.
authors: Alexandra J
authors: AJ
authors: Harvey
authors: Department of PhysiologySchool of BioSciencesThe University of Melbourne, Parkville, Victoria 3010, AustraliaDepartment of Obstetrics and GynaecologyMercy Hospital, The University of Melbourne, Heidelberg, Victoria 3084, Australia.
authors: John R
authors: JR
authors: Sheedy
authors: Department of PhysiologySchool of BioSciencesThe University of Melbourne, Parkville, Victoria 3010, AustraliaDepartment of Obstetrics and GynaecologyMercy Hospital, The University of Melbourne, Heidelberg, Victoria 3084, Australia Department of PhysiologySchool of BioSciencesThe University of Melbourne, Parkville, Victoria 3010, AustraliaDepartment of Obstetrics and GynaecologyMercy Hospital, The University of Melbourne, Heidelberg, Victoria 3084, Australia.
authors: Natalie J
authors: NJ
authors: Hannan
authors: Department of PhysiologySchool of BioSciencesThe University of Melbourne, Parkville, Victoria 3010, AustraliaDepartment of Obstetrics and GynaecologyMercy Hospital, The University of Melbourne, Heidelberg, Victoria 3084, Australia.
authors: David K
authors: DK
authors: Gardner
authors: Department of PhysiologySchool of BioSciencesThe University of Melbourne, Parkville, Victoria 3010, AustraliaDepartment of Obstetrics and GynaecologyMercy Hospital, The University of Melbourne, Heidelberg, Victoria 3084, Australia m.wlodek@unimelb.edu.au.
authors: Mary E
authors: ME
authors: Wlodek
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D011247:Pregnancy; D051381:Rats; D001755:Blastocyst / Q000166:cytology / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D002478:Cells, Cultured; D047108:Embryonic Development; D005317:Fetal Growth Retardation / Q000209:etiology; D007333:Insulin Resistance; D008423:Maternal Age; D009929:Organ Size; D011921:Rats, Inbred WKY; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D000831:Animals, Newborn
chemical_list: D001786:Blood Glucose; D012333:RNA, Messenger