Neonatal thymulin gene therapy prevents the characteristic ovarian atrophy of adult nude mice

REGGIANI PC; BARBEITO CG; FLAMINI MA; RODRÍGUEZ SS; CONSOLE GM; DARDENNE M; GOYA RG

Río de Janeiro, Brasil

Congreso; ISNIM 2008; 2008

The International Society for Neuroinmunomodulation

Introduction: The endocrine thymus is involved in reproductive maturation. Thus, congenitally athymic (nude) female mice show reduced levels of circulating gonadotropins and a number of reproductive derangements after puberty. Since the thymic hormone thymulin (FTS-Zn) has hypophysiotropic activity, it was of interest to determine whether neonatal thymulin gene therapy (NTGT) can prevent the reproductive derangements of adult nudes. Initially, we constructed an adenoviral vector (RAd-FTS) expressing a synthetic gene for thymulin and showed that NTGT restores serum thymulin and prevents gonadotropin deficiency in adult nudes. In the present study we aimed at determining whether NTGT in female nudes can prevent ovarian dysgenesis. Methodology and Results: RAd-FTS or RAd-GFP (control vector) were i.m. injected (108 pfu) to newborn female nu/+ and nu/nu (athymic) mice. At 70 days of age, mice were bled and sacrificed; ovaries and pituitary were submitted to histomorphometric analysis. Serum thymulin and estrogen levels were measured by a bioassay and RIA, respectively. NTGT in athymic mice restored their serum thymulin levels (256±80,9 vs 8±0,5 (control) fg/ml (p<0,01)). Furthermore, NTGT prevented totally or partially, the typical deficiency in the number of secondary (p<0.01) and tertiary (p<0.15) follicles, and of corpora lutea (p<0.05), in adult nu/nu, also preventing the increase in the number of atretic follicles in athymic mice (nu/nu treated vs nu/nu controls, P<0.001). The typical serum E2 deficiency of adult nu/nu females was partially prevented by NTGT. Conclusions: Thymulin plays a relevant role in the maturation of the thymus-pituitary-gonadal axis.