Impact of metabolic syndrome on murine fetal programming

Abstract

In Argentina, metabolic syndrome (MS) is a highly prevalent pathology (30%), even during pregnancy. There exist several studies that investigate maternal malnutrition (hypo/ hypernutrition) on offspring development, showing that perinatal nutritional challenges exert long-lasting consequences in the development and reproductive function of the offspring. It remains unknown, if MS exerts similar effects. Using a rat model of induced MS, we aim to investigate whether this pathology is a reproductive fetal programmer.

Female Wistar rats (60 days old) were randomly divided into two groups: a) controls (C): pelleted chow + water or, b) MS: pelleted chow + 10% fructose (v/v) in water, which is a validated MS inductor protocol. Treatment was applied from 4 weeks before intercourse to weaning of the offspring (postnatal day 21).

MS was verified in an initial group of dams (5 dams/treatment) with statistically higher values ​​(p <0.05) of total cholesterol (mg/dl) (MS= 87.9±1.6 vs C= 65.0±6.4), triglycerides (mg dl) (MS= 136.2±18.3 vs C= 79.5±11.9) and LDL (mg/dl) (MS= 24.3±4.5 vs C= 9.8±3.5). Furthermore, SM dams gain significantly more weight (g) (MS= 35.5±3.4 vs C= 23.9±3.7) and exhibited more visceral fat (g) (MS= 11.7±2.3 vs C= 6.4±1.3). MS did neither modify pregnancy duration, litter size, nor pups weigth at birth. In the offspring, MS tended to accelerate the onset of somatic and neurobiological parameters, and to increase more body weight gain than C. Furthermore, MS significantly advanced vaginal opening (on day 28: MS= 46.7±29.0% vs C= 10.0±5.0%) and testicular descent (on day 19: MS= 100.0±0.0% vs C= 11.67±5.43%; n=3- 4 litters/treatment; p <0.05). At adulthood, no differences were observed in male reproductive function. In females from MS dams, an increase in ovulation index was observed (MS= 15.0±0.4; C=12.23±0.5; n=10-12 females/group, p<0.05). Besides, 100% of the SM female litter lost at least one embryo vs 18% of C females.

We are currently exploring the cellular/molecular bases of these results.