Avaliação de parâmetros reprodutivos e caracterização morfológica da placenta de camundongos gestantes deficientes do ‘fator de troca de nucleotídeos guanina para a proteínas Ras’ RASGEF1B

Abstract

The technique to obtain knockout animals revolutionized the field of genetics, allowing the study of the function of a gene through the comparison between a wild animal and another with the deleted gene. Several gene functions have been discovered with this technique, but many genes and their functions in different tissues still need to be elucidated, among them Rasgef1b. This gene encodes for a guanine nucleotide exchange factor of Ras-like GTPases, which control the activation of signaling pathways important in the regulation of various metabolic processes such as cell proliferation and survival. Although RasGEF1b expression occurs predominantly in macrophages, it can be detected, even at lower levels, in other tissues such as the placenta. The placenta is a crucial organ in the prenatal development of mammals, since it is responsible for the maternal-fetal interface, a region of exchange of nutrients and respiratory gases. Moreover, it is extremely sensitive to disturbances, and there is evidence that different genes play critical roles on its morphofunctionality. Therefore, studying the placenta and reproductive parameters of females lacking the RasGEF1b factor is a promising and novel way to investigate the role of this gene on reproductive capacity. To this end, wild-type and RasGEF1b-KO female mice were evaluated for reproductive parameters before and during gestation, at which time their placentas were collected (gestational day 17.5) for histomorphometrical analyses. RasGEF1b-KO females had similar estrous cycle and pregnancy rate to WT females (P>0.05). Additionally, they showed fewer fetuses and resorptions (P<0.05). Fetuses from knockout females showed similar biometrics to fetuses from WT females. However, placentas from knockout animals showed biometric and histological differences, such as higher weight, smaller diameter and efficiency, and a higher proportion of fetal vessels in the labyrinth and maternal vessels in the junctional zone, thicker interheme membrane, and larger fetal vessels (P<0.05). Our data demonstrate, in an unprecedented manner, the reproductive and placental alterations arising from RasGEF1b factor deficiency in murine females.