Metabolic syndrome in dams and fetal programming

a study in a murine model

Abstract

Metabolic syndrome (MS) is a highly prevalent in our country, even in women at gestational age. However, its potential impact as a fetal programmer was rarely evaluated. The hypothesis of our study was that dams MS alters the development of the offspring, impacting on litters growth and postnatal development. Hence, we studied in a model of pregnant rats (F0) with MS, the effects of this pathology on: 1) pregnancy rate, duration of gestation and litter size and weight; 2) physical, neurobiological and sexual development of the offspring (F1) and 3) reproductive function of the F1 in adulthood.

We used adult female Wistar rats, randomly divided into two groups: a) controls (C): pelleted food + water; and b) SM: pelleted food + water with 10% fructose; n=8 animals/treatment. The treatment was applied from 4 weeks previous to copula, until pups weaning. Results were analyzed with ANOVA, repeated measures ANOVA or Chi-square, as appropriate, and p≤0.05 as significance level.

In F0, MS was verified with a significant increase in total cholesterol (MS=87.9±1.6mg/dl vs C=65.0±6.4mg/dl), triglycerides (MS=136.2±18.3mg /dl vs C=79.5±11.9mg/dl), LDL (SM=24.3±4.5mg/dl vs C=9.8±3.5mg/dl) and TG/HDL (SM=4 .1±0.7 vs C= 2.0±0.1). Furthermore, these females gained significantly more weight (SM=35.5±3.4g vs C=23.9±3.7g) and had more visceral fat (SM=11.7±2.3g vs C=6.4 ±1.3g). In F1, SM increased significantly body weight gain of male pups (SM=59.52±0.66g vs C=49.67±2.24g) and advanced vaginal opening (day 28: SM=46, 7±29.0% vs C=10.0±5.0%) and testicular descent (day 19: SM=100.0±0.0% vs C=11.67±5.43%); n=6-4 litters/treatment. In adulthood, F1 female pups from the SM group (n=12) showed, at gestation day 18, significantly increased body weight (SM=280.4±3.9g vs C=251.5±7.0g without pups), higher amounts of corpora lutea (SM=15.00±0.4 vs C=12.25±0.5), heavier fetuses (SM=2.2±0.2g vs C=1.7±0.2g) and higher frequency of embryonic loss (SM=13.3±4.5% vs C=3.6±1.2%) than control pups (n=10).

Under our experimental conditions, it can be confirmed that MS acts as a fetal programmer, modeling the physical and sexual development of the offspring and the reproductive function of the female pups in adulthood.