The Effect of Maternal High-Fat Diet and ART on Cardiovascular Outcome in Offspring.

Abstract

The Barker Hypothesis states that the maternal environment a fetus is exposed to can affect its subsequent development. Two examples of suboptimal maternal environments found in women today are those created by obesity and Assisted Reproductive Technologies (ART). Obesity affects approximately 300 million people world-wide, and over one-third of women of reproductive age in the United States are obese. ART is used to overcome infertility; a problem that nearly ten percent of women in the United States face. These suboptimal maternal environments have been associated with unfavorable outcomes in the offspring such as cardiovascular disease and insulin resistance. Therefore, for the present study we hypothesized that obesity and ART independently and synergistically can adversely affect the cardiovascular health of the offspring. We examined the effects that maternal consumption of a high (HF) or low (LF) fat diet prior to and during pregnancy in combination with the use of ART (i.e. superovulation, embryo culture, and embryo transfer) or no ART would have on the cardiovascular performance of juvenile offspring in mice. Embryo cultures were performed in either KSOM supplemented with amino acids or in Whitten's medium. Blastocysts were transferred into pseudopregnant females fed either a HF or LF diet. In addition, we challenged the offspring generated from that scheme to either a HF or LF diet after weaning to assess if offspring diet would exacerbate or ameliorate cardiovascular problems resulting from being gestated in a HF environment and/or conceived by ART (in all 40 permutations were attempted). The offspring were sacrificed on average at 7 weeks, and the measurements taken were body weight, blood pressure (by carotid artery catheterization), and resistance vessel vasoconstriction- to norepinephrine [10-8 to 10-5M]- or vasodilation- to acetylcholine or sodium nitroprusside [10−8 to 10−5 or 10−7 to 10−4M; respectively]. Results indicate that mice that developed in Whitten's medium during preimplantation development had greater body weight at seven weeks of age when compared to mice cultured in KSOM or those conceived without the use of ART (control female = 21.40 ± 1.1, KSOM female = 24.10 ± 1.3, Whitten's female = 27.80 ± 1.6, control male = 29.30 ± 1.2, KSOM male = 30.00 ± 1.6, Whitten's male = 36.30 ± 1.6 g; P < 0.01). These results were not confounded by consumption of HF diet at any stage during the experiment. Further, we observed that a group of ART males in the HF diet had higher mean arterial pressure when compared to controls (102.7 ± 6.17 and 74.8 ± 5.24 and mmHg, respectively; P < 0.02). We found that when offspring of obese dams were fed a HF diet, they had increased body weight (P<0.05) and their resistance arteries had greater (P<0.05) vasconstrictive responses to norepinephrine than those from control mice. Differences were observed between males and females that had been exposed to a high fat maternal and offspring diet for body weight (P<0.05) and response to acetylcholine (endothelium dependent response; P<0.05). However, diet did not differently affect the response to sodium nitroprusside (endothelium independent response) between sexes. Together, these data suggest an interaction between the uterine environment and the health of the offspring.