Implicações do consumo crônico de dieta hipoproteica durante a gestação sobre a foliculogênese, a morfologia placentária e suas consequências sobre a prole em camundongos heterogênicos

Abstract

Maternal protein intake deserves special attention since proper fetal development is dependent on maternal nutritional status, and the placenta mediates such interactions. Information on impacts of chronic low protein intake during pregnancy in outbred populations is limited. To evaluate ovarian and placental morphological alterations under chronic maternal low protein intake, adult Swiss outbred female mice were fed either low (TT) or normal (CC) protein diets. Biometrical data were obtained, tissues were processed for histomorphometrical evaluation at gestational days (GD) 7.5 and 17.5. At GD17.5, proliferative and apoptotic indices, autophagy and its regulation were evaluated in placentae through Ki67, DNA fragmentation, Lc3 and Bcl-2 markers, respectively. Even though the estimated follicle population was similar between experimental groups at GD7.5 and 17.5, greater proportion of atretic follicles was observed at GD7.5 (P<0.05), oocytes from secondary and tertiary follicles at GD7.5 were larger (P<0.05) and secondary follicles and their oocytes were smaller at GD17.5 (P<0.05) in TT females. No alterations were found at GD 7.5, but placentae from the TT group were lighter and smaller (P<0.05), although efficiency, proportion of layers, cell proliferative and death percentages were not affected at GD17.5. Autophagy and its regulation were similar, and Lc3 and Bcl-2 proteins were simultaneously localized to glycogen cells of the junctional zone. Fetuses from the TT group were smaller, presented higher prevalence of relative weight frequency in the 10th-25th percentiles, lower frequency above the 75th percentile, and exhibited higher brain:liver weight ratio and lower liver:body weight ratio (P<0.05). Even though size and relative weight frequency were similar in both groups at birth, liver:body weight ratio was lower in TT newborn (P<0.01). Thus, the present results reveal that even though chronic protein malnutrition does not affect fertility, it compromises folliculogenesis. Additionally, placental morphological aspects are preserved in outbred mice to meet fetal growth demands and ensure adequate newborn weight. However, fetal growth impairment affects organ development, predisposing to chronic adult diseases and deserves further investigation.