Efeito da restrição alimentar materna durante a lactação sobre a função ovariana da prole fêmea na puberdade e vida adulta

Abstract

The goal of this study was to evaluate if maternal malnutrition during lactation alters the ovarian function of offspring at puberty and adulthood. At parturition, dams were randomly assigned to the following groups: (C) control group, with free access to a standard laboratory diet containing 23% protein and (PER) protein-restricted group, with free access to an isoenergy and protein-restricted diet containing 8% protein. After weaning, the female pups had free access to standard laboratory diet until the end of experiment. Then, only the animals on the diestrum stage were sacrificed with a lethal dose of pentobarbital at 40 and 90 days of age. The blood was collected by cardiac puncture and the serum was used to determine hormonal levels by radioimmunoassay. The right ovaries were excised, weighted and kept at -80 ºC for subsequent measurements of androgen receptor (AR), estrogen receptors (ERα, ERβ1 and ERβ2), follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), leptin receptor isoforms (Ob-R, Ob-Ra and Ob-Rb), and aromatase transcripts by RT-PCR. The left ovary was paraffin embedded, sectioned at 5 μm thickness and processed by routine histological analyses, for morphologic classification of follicles. At puberty, the PER group presented a significant increase (p<0.01) in the number of preantral and small antral follicles and decrease (p<0.01) in the number of primordial, and Graafian follicles and corpus luteum. The estradiol serum concentration (pg/ml) was significantly higher (p<0.05). There was a significant increase (p<0.05) in the amount of FSHR and LHR transcripts and a significant decrease in the amount of AR (p<0.05), ERα (p<0.05), ERβ1 (p<0.05), and ERβ2 (p<0.05) transcripts. At adult life, the maternal malnutrition caused a reduction in the number of all ovarian follicles, however this reduction was significant only in the primordial, primary, and Graffian follicles (p<0.05) number. There was a decrease in the aromatase (p<0.01), FSHR (p<0.05), LHR (p<0.05), Ob-R (p<0.05) and Ob-Rb (p<0.05) transcripts. We can conclude that maternal malnutrition during lactation programs the ovary of offspring by altering folliculogenesis, and the expression of the different isoforms of estrogen, leptin, androgen and gonadotropins receptors and the aromatase enzyme. This metabolic programming can possibly be due the low levels of leptin in the first days of life and can contribute to an early senescence and reduction of fertility already seen in the literature.