Effects of the use of assisted reproduction and high-caloric diet consumption on body weight and cardiovascular health of juvenile mouse offspring

Abstract

Maternal obesity and the use of assisted reproductive technologies (ART) are two suboptimal developmental environments that can lead to offspring obesity and cardiovascular disease. We hypothesized that these environments independently and synergistically adversely affect the offspring’s weight and cardiovascular performance at ∼7 weeks of age. Mice were fed either 24% fat and 17.5% high fructose corn syrup (HF) or maintenance chow (5% fat; LF). Dams were subdivided into no-ART and ART groups. ART embryos were cultured in Whitten’s medium and transferred into pseudopregnant recipients consuming the same diet as the donor. Offspring were fed the same diet as the mother. Body weights (BW) were measured weekly and mean arterial pressure (MAP) was collected through carotid artery catheterization at sacrifice (55 ± 0.5 days old). Expression of genes involved in cardiovascular remodeling was measured in thoracic aorta using qRT-PCR, and levels of reactive oxygen species were measured intracellularly and extracellularly in mesenteric resistance arteries. ART resulted in increased BW at weaning. This effect decreased over time and diet was the predominant determinant of BW by sacrifice. Males had greater MAP than females (p=0.002) and HF consumption was associated with greater MAP regardless of sex (p<0.05). Gene expression was affected by sex (p<0.05) and diet (p<0.1). Lastly, the use of ART resulted in offspring with increased intracellular ROS (p=0.05). In summary, exposure to an obesogenic diet pre- and/or post-natally affects weight, MAP, and gene expression while ART increases oxidative stress in mesenteric resistance arteries of juvenile offspring, no synergistic effects were observed.

Lower Doses of Fructose Extend Lifespan inCaenorhabditis elegans

“…Since HFCS intake increased 10-fold in the United States from 1970 to 1990 and accounts for 40% of the consumption of caloric sweeteners, the correlation between increased HFCS consumption and increased obesity has been speculated to have a cause and effect relationship (Bray et al, 2004). Consumption of sucrose decreased 50% as HFCS consumption increased during this time period (DiMeglio and Mattes, 2000, Ludwig et al, 2001, Elliott et al, 2002, Raben et al, 2002, Bray et al, 2004, Johnson et al, 2007, Schenewerk et al, 2014). …”

“…Obesity associated health issues are increasing globally, including cardiovascular disease, hypertension, stroke, type 2 diabetes, insulin resistance, impaired glucose tolerance, hyperinsulinemia, hypertriglyceridemia, nonalcoholic fatty liver disease, and ovarian or colorectal cancer (Gerstein, 1997, DiMeglio and Mattes, 2000, Ludwig, Peterson, & Gortmaker, 2001, Elliott et al, 2002, Raben et al, 2002, Bray, Nielsen, & Popkin, 2004, Cordain et al, 2005, Johnson et al, 2007, Schenewerk et al, 2014, Zhang et al, 2014). …”

Maternal Hyperleptinemia Is Associated with Male Offspring’s Altered Vascular Function and Structure in Mice

“…To determine if maternal hyperleptinemia altered offspring blood pressure, systolic and diastolic blood pressures were measured in juvenile (6 week old) and adult male (31 week old) offspring from WT-control and Lepr db/+ dams using a tail cuff CODA non-invasive blood pressure system (Kent Scientific, Torrington CT, USA) as well as by carotid catheter under anesthesia as previously described [ 40 ]. For tail-cuff measurements, individual animals were placed in a commercially acquired restraining tube and allowed to acclimatize for 10 minutes prior to initiating the blood pressure measurement protocol.…”

“…For tail-cuff measurements, individual animals were placed in a commercially acquired restraining tube and allowed to acclimatize for 10 minutes prior to initiating the blood pressure measurement protocol. For the invasive blood pressure measurements, mice were anesthetized with inhaled isoflurane and while under surgical plane anesthesia at 2% isoflurane, a carotid artery was cannulated and arterial pressure measured using a PowerLab data acquisition system and LabChart software (ADInstruments) as previously described [ 40 ].…”

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

“…Donjacour et al demonstrated reduced systolic blood pressure and enlarged left heart in male mice produced after IVF and suboptimal embryo culture conditions [56]. In contrast, blood pressure changes were not observed in a different study that also targeted embryo culture procedures [57,58]. However, under high fat diet conditions, mice produced from superovulation and subsequent culture of embryos that were fertilized in vivo exhibited impaired endothelial-dependent artery vasodilation and vasculature structural changes [58].…”