314 FECAL STEROID HORMONES IN 3 × TG-AD AND WILD-TYPE MICE AND THEIR RELATION WITH FERTILITY

Abstract

Extracellular deposition of amyloid peptides in plaques and neurofibrillary tangles are 2 characteristic pathological features of Alzheimer’s disease (AD). These models show the neuropathological symptoms and the hormonal changes. It has been observed that the pathology appears with age and gets worse progressively. Several studies have proved the neuroprotective action of the androgens and estrogens related to age. The aim of this study was reveal if aging in 3 × TG-AD transgenic mice produces a change in the androgen and estrogen levels, compared with the wild type (WT), and if these changes could influence fertility. In this experiment, we have used male and female WT (n = 40) and 3 × TG-AD transgenic (n = 40) mice for gene PS1 (involved in the acceleration of the amyloid plaque formation), tau (involved in neurodegeneration), and APP (involved in the extracellular accumulation of fi-amyloid protein). We have studied mice of different ages: 3, 4, 7, and 8 months old. Fecal samples were collected 5 days every week (between 0900-1000 h). The technique used for the hormone quantification was ELISA. Results were calculated in ngg^-1 of feces. The statistical analysis was done with the Origin 8 program (Software Cientifico, Castellana, Madrid, Spain), through a 1-way ANOVA. Results were represented with the mean ± standard error (P < 0.05 values were considered statistically significant). The pregnancy rate in transgenic mice before 4 months old was 0%, whereas in WT mice, the fertility rate was 82%. At 8 months, the pregnancy rate in transgenic mice was 65% and in WT 88%. In males, although androstenedione (A4) concentrations were not significant through age, testosterone levels increased significantly in transgenic mice, but not in WT mice. Estrogens presented the biggest differences between groups. The 3-month-old transgenic mice showed significantly higher values, and this elevation of the estrogens could be the cause of infertility in transgenic mice. At 8 months, the values decreased significantly in WT mice, whereas in transgenic mice, the concentrations were higher, and this could be the reason for the differences in the fertility rate. In females, A4 concentrations were higher in WT mice, showing a significant increase with age in both groups. Testosterone concentrations were significantly higher with age in transgenic mice. These mice showed the higher estrogen concentrations, showing a decrease with age in both groups that was significant in transgenic mice. Increase of testosterone in 3-month-old transgenic mice could be the reason for the infertility in the females. In conclusion, the fecal analysis is a noninvasive method, appropriate for androgen and estrogen determination in the different types of mice. There are several differences in the androgen and estrogen levels between the 2 groups of studied mice; the levels are generally more elevated in transgenic mice. Gene modification in 3 × TG-AD transgenic mice could cause a delay in the onset of puberty.