title: Embryo transfer cannot delineate between the maternal pregnancy environment and germ line effects in the transgenerational transmission of disease in rats.
abstract: Adverse conditions in utero can have transgenerational effects, in the absence of a subsequent insult. We aimed to investigate the contribution of the maternal pregnancy environment vs. germ line effects in mediating alterations to cardiorenal and metabolic physiology in offspring from mothers born small. Uteroplacental insufficiency was induced by bilateral uterine artery and vein ligation (Restricted group) or sham surgery (Control group) in Wistar-Kyoto rats. Restricted and control female offspring (F1) were mated with either breeder males (embryo donor) or vasectomized males (embryo recipient). Embryo transfer was performed at embryonic day (E) 1, whereby second-generation (F2) embryos gestated (donor-in-recipient) in either a control (Cont-in-Cont, Rest-in-Cont) or restricted (Cont-in-Rest, Rest-in-Rest) mother. In male and female offspring, glomerular number and size were measured at postnatal day (PN) 35, and systolic blood pressure, glucose control, insulin sensitivity, and pancreatic β-cell mass were measured in separate sibling cohorts at 6 mo. Rest-in-Rest offspring were hypothesized to have similar characteristics (reduced growth, altered metabolic control, and hypertension) to non-embryo-transferred Rest, such that embryo transfer would not be a confounding experimental influence. However, embryo-transferred Rest-in-Rest offspring underwent accelerated growth during the peripubertal phase, followed by slowed growth between 2 and 3 mo of age compared with non-embryo-transferred Rest groups. Furthermore, renal function and insulin response to a glucose load were different to respective non-embryo-transferred groups. Our data demonstrate the long-term effects of in vitro embryo manipulation, which confounded the utility of this approach in delineating between the maternal pregnancy environment and germ line effects that drive transgenerational outcomes.
authors: Department of Physiology, The University of Melbourne, Parkville, Australia;
authors: Melanie
authors: M
authors: Tran
authors: Linda A
authors: LA
authors: Gallo
authors: Alanna N
authors: AN
authors: Hanvey
authors: Andrew J
authors: AJ
authors: Jefferies
authors: Kerryn T
authors: KT
authors: Westcott
authors: Luise A
authors: LA
authors: Cullen-McEwen
authors: David K
authors: DK
authors: Gardner
authors: Karen M
authors: KM
authors: Moritz
authors: Mary E
authors: ME
authors: Wlodek
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004624:Embryo Transfer / Q000379:methods; D005260:Female; D005854:Germ Cells / Q000378:metabolism*; D005951:Glucose Tolerance Test / Q000379:methods; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D010927:Placental Insufficiency / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011921:Rats, Inbred WKY; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: blood pressure; glucose tolerance; kidney function; low birth weight