Faria Tatiane da Silva, Brasil Flávia de Bittencourt, Sampaio Francisco J B, Ramos Cristiane da Fonte
Urogenital Research Unit-UERJ, State University of Rio de Janeiro, Avenue 28 de Setembro, Rio de Janeiro, RJ, Brazil.
J Endocrinol. 2008 Sep;198(3):625-34. doi: 10.1677/JOE-08-0121. Epub 2008 Jul 2.
In this study, we aimed to evaluate whether maternal malnutrition during lactation alters the folliculogenesis and the expression of the gonadotropins and estrogen isoforms ovarian receptors in the offspring at puberty. At parturition, dams were randomly assigned to the following groups: control (C) group, with free access to a standard laboratory diet containing 23% protein and protein-energy-restricted (PER) 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. The maternal malnutrition caused a significant increase in the number of preantral (C=13.72+/-2.87; PER=26.36+/-3.03, P<0.01) and small antral follicles (C=9.32+/-1.35; PER=17.64+/-2.33, P<0.01) and decrease in the number of primordial (C=11.72+/-1.37; PER=3.92+/-0.60, P<0.01) and Graafian follicles (C=1.84+/-0.21; PER=0.96+/-0.11, P<0.01), and corpus luteum (C=2.00+/-0.28; PER=0.80+/-0.31, P<0.01). The estradiol serum concentration was significantly higher (C=67.86+/-4.39; PER=83.29+/-2.68, P<0.05) while testosterone serum concentration did not show statistical difference (C=0.09+/-0.02; PER=0.11+/-0.01, P>0.05) in the PER group. In relation to the receptors expression, maternal malnutrition led to a significant increase in the amount of Fshr (C=0.89+/-0.04; PER=1.07+/-0.03, P<0.05) and Lhcqr (C=0.87+/-0.15; PER=1.33+/-0.08, P<0.05) transcripts and a significant decrease in the amount of Ar (C=0.59+/-0.006; PER=0.13+/-0.080, P<0.05), ER alpha (Esr1) (C=3.33+/-0.71; PER=0.74+/-0.50, P<0.05), ER beta 1 (Esr2) (C=1.33+/-0.06; PER=0.49+/-0.36, P<0.05), and ER beta 2 (Esr2) (C=3.28+/-0.60; PER=0.62+/-0.34, P<0.05) transcripts. In conclusion, perinatal maternal malnutrition can directly affect folliculogenesis at puberty probably as a consequence of changes in the ovarian expression of gonadotropins, androgen and estrogens isoforms receptors. Long-term sexual alterations could be expected in this experimental model, since a reduction in the primordial follicle number is observed, which can result in a decrease in the reproductive lifetime and an earlier termination of breeding capacity.
在本研究中，我们旨在评估哺乳期母体营养不良是否会改变后代青春期时的卵泡生成以及促性腺激素和雌激素亚型卵巢受体的表达。分娩时，将母鼠随机分为以下几组：对照组（C组），可自由摄取含23%蛋白质的标准实验室饮食；蛋白质 - 能量限制（PER）组，可自由摄取含8%蛋白质的等能量和蛋白质限制饮食。断奶后，雌性幼鼠可自由摄取标准实验室饮食。母体营养不良导致初级卵泡数量显著增加（C组 = 13.72 ± 2.87；PER组 = 26.36 ± 3.03，P < 0.01）和小窦状卵泡数量增加（C组 = 9.32 ± 1.35；PER组 = 17.64 ± 2.33，P < 0.01），而原始卵泡数量（C组 = 11.72 ± 1.37；PER组 = 3.92 ± 0.60，P < 0.01）、格拉夫卵泡数量（C组 = 1.84 ± 0.21；PER组 = 0.96 ± 0.11，P < 0.01）和黄体数量（C组 = 2.00 ± 0.28；PER组 = 0.80 ± 0.31，P < 0.01）减少。PER组的雌二醇血清浓度显著更高（C组 = 67.86 ± 4.39；PER组 = 83.29 ± 2.68，P < 0.05），而睾酮血清浓度无统计学差异（C组 = 0.09 ± 0.02；PER组 = 0.11 ± 0.01，P > 0.05）。关于受体表达，母体营养不良导致促卵泡激素受体（Fshr）（C组 = 0.89 ± 0.04；PER组 = 1.07 ± 0.03，P < 0.05）和黄体生成素受体（Lhcqr）（C组 = 0.87 ± 0.15；PER组 = 1.33 ± 0.08，P < 0.05）转录本数量显著增加，而雄激素受体（Ar）（C组 = 0.59 ± 0.006；PER组 = 0.13 ± 0.080，P < 0.05）、雌激素受体α（Esr1）（C组 = 3.33 ± 0.71；PER组 = 0.74 ± 0.50，P < 0.05）、雌激素受体β1（Esr2）（C组 = 1.33 ± 0.06；PER组 = 0.49 ± 0.36，P < 0.05）和雌激素受体β2（Esr2）（C组 = 3.28 ± 0.60；PER组 = 0.62 ± 0.34，P < 0.05）转录本数量显著减少。总之，围产期母体营养不良可能由于促性腺激素、雄激素和雌激素亚型受体的卵巢表达变化，直接影响青春期的卵泡生成。在这个实验模型中，可以预期会出现长期的性改变，因为观察到原始卵泡数量减少，这可能导致生殖寿命缩短和繁殖能力提前终止。
