Envelhecimento ovariano em camundongos com knockout no receptor do hormônio do crescimento suplementados com 17α- Estradiol

Abstract

Mice with growth hormone (GH) receptor gene disruption (GHRKO) have absent GH activity. These mice are the main model to access the effects of GH and are known for having extended lifespan and female reproductive longevity. 17α- estradiol (17α-E2) is a molecule reported to extend mice lifespan. Hence, the aim of this study was to evaluate the ovarian reserve, in ovaries of normal and GHRKO mice supplemented or not with 17α-estradiol. Our hypothesis was that GHR disruption and 17α-Estradiol treatment would decrease the activation of primordial follicles in a complementary way in mice. Six GHRKO mice and six wild-type (WT) mice were divided into four groups: GHRKO mice normal diet (GHRKO; n=3), GHRKO mice supplemented with 17α-E2 (GHRKO-E2; n=3), WT mice normal diet (WT; n=3) and WT mice supplemented with 17α-E2 (WT-E2; n=3). E2 was provided in the food for four months. Histological slides were prepared from the mice ovaries. Images of the ovarian sections were captured by a camera coupled to a microscope, and the follicles were counted and measured. The statistical analysis considered the effect of the genotype (GHRKO vs WT), treatment (E2 vs CONT) and its interaction. Both genotype (p=0.0117) and diet (p=0.0136) had effects on the number of primordial follicles count as well as the interaction between them (p=0.004). The number of primordial follicles was higher on the GHRKO-CONT group (2632±181) than in the other groups. 17α-E2 treatment reduced the number of primordial follicles in the GHRKO mice to a level similar to WT, but had no effect on WT mice. WT mice had a higher number of primary follicles than GHRKO mice (p=0.006). 17α-E2 diet exerted no effect on the number of primary follicles (p=0.785). In summary, nontreated GHRKO mice had an increased primordial follicle reserve than WT mice. However, the genotypes treated with 17α-E2 responded differently, GHRKO decreased the primordial follicle reserve and WT mice maintained the primordial follicles number, which indicates that 17α-E2 has a differential role on follicle activation when there is a lack of GH /IGF-I.