Embryo transfer cannot delineate between the maternal pregnancy environment and germ line effects in the transgenerational transmission of disease in rats

摘要: Adverse conditions in utero can have transgenerational effects, the absence of a subsequent insult. We aimed to investigate contribution maternal pregnancy environment vs. germ line effects mediating alterations cardiorenal and metabolic physiology offspring from mothers born small. Uteroplacental insufficiency was induced by bilateral uterine artery vein ligation (Restricted group) or sham surgery (Control Wistar-Kyoto rats. Restricted control female (F1) were mated with either breeder males (embryo donor) vasectomized recipient). Embryo transfer performed at embryonic day (E) 1, whereby second-generation (F2) embryos gestated (donor-in-recipient) (Cont-in-Cont, Rest-in-Cont) restricted (Cont-in-Rest, Rest-in-Rest) mother. In male offspring, glomerular number size measured postnatal (PN) 35, systolic blood pressure, glucose control, insulin sensitivity, pancreatic β-cell mass separate sibling cohorts 6 mo. Rest-in-Rest hypothesized similar characteristics (reduced growth, altered hypertension) non-embryo-transferred Rest, such that embryo would not be confounding experimental influence. However, embryo-transferred underwent accelerated growth during peripubertal phase, followed slowed between 2 3 mo age compared Rest groups. Furthermore, renal function response load different respective Our data demonstrate long-term vitro manipulation, which confounded utility this approach delineating drive outcomes.