Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Department of Biochemistry & Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
J Cachexia Sarcopenia Muscle. 2022 Aug;13(4):2175-2187. doi: 10.1002/jcsm.12986. Epub 2022 May 18.
Fetal stage is a critical developmental window for the skeletal muscle, but little information is available about the impact of maternal vitamin D (Vit. D) deficiency (VDD) on offspring lean mass development in the adult life of male and female animals.
Female rats (Wistar Hannover) were fed either a control (1000 IU Vit. D3/kg) or a VDD diet (0 IU Vit. D3/kg) for 6 weeks and during gestation and lactation. At weaning, male and female offspring were randomly separated and received a standard diet up to 180 days old.
Vitamin D deficiency induced muscle atrophy in the male (M-VDD) offspring at the end of weaning, an effect that was reverted along the time. Following 180 days, fast-twitch skeletal muscles [extensor digitorum longus (EDL)] from the M-VDD showed a decrease (20%; P < 0.05) in the number of total fibres but an increase in the cross-sectional area of IIB (17%; P < 0.05), IIA (19%; P < 0.05) and IIAX (21%; P < 0.05) fibres. The fibre hypertrophy was associated with the higher protein levels of MyoD (73%; P < 0.05) and myogenin (55% %; P < 0.05) and in the number of satellite cells (128.8 ± 14 vs. 91 ± 7.6 nuclei Pax7 + in the M-CTRL; P < 0.05). M-VDD increased time to fatigue during ex vivo contractions of EDL muscles and showed an increase in the phosphorylation levels of IGF-1/insulin receptor and their downstream targets related to anabolic processes and myogenic activation, including Ser Akt and Ser GSK-3β. In such muscles, maternal VDD induced a compensatory increase in the content of calcitriol (two-fold; P < 0.05) and CYP27B1 (58%; P < 0.05), a metabolizing enzyme that converts calcidiol to calcitriol. Interestingly, most morphological and biochemical changes found in EDL were not observed in slow-twitch skeletal muscles (soleus) from the M-VDD group as well as in both EDL and soleus muscles from the female offspring.
These data show that maternal VDD selectively affects the development of type-II muscle fibres in male offspring rats but not in female offspring rats and suggest that the enhancement of their size and fatigue resistance in fast-twitch skeletal muscle (EDL) is probably due to a compensatory increase in the muscle content of Vit. D in the adult age.
胎儿期是骨骼肌发育的关键时期，但关于母体维生素 D（Vit. D）缺乏（VDD）对雄性和雌性动物成年后代瘦体重发育的影响，相关信息十分有限。
雌性大鼠（Wistar 哈瑙）分别用对照（1000 IU Vit. D3/kg）或 VDD 饮食（0 IU Vit. D3/kg）喂养 6 周，并在妊娠和哺乳期进行喂养。断奶时，雄性和雌性后代被随机分开，并接受标准饮食直至 180 天。
维生素 D 缺乏症导致雄性（M-VDD）后代在断奶结束时发生肌肉萎缩，这种影响随着时间的推移而逆转。在 180 天后，M-VDD 的快肌（伸趾长肌（EDL））纤维总数减少（20%；P<0.05），但 IIB（17%；P<0.05）、IIA（19%；P<0.05）和 IIAX（21%；P<0.05）纤维的横截面积增加。纤维肥大与肌源性分化因子（MyoD）（73%；P<0.05）和生肌调节因子（myogenin）（55%；P<0.05）的蛋白水平升高以及卫星细胞数量增加（128.8±14 个 Pax7+细胞核比 M-CTRL 中的 91±7.6 个；P<0.05）有关。M-VDD 增加了 EDL 肌肉体外收缩时的疲劳时间，并增加了与合成代谢过程和肌原性激活相关的 IGF-1/胰岛素受体及其下游靶标的磷酸化水平，包括 Ser Akt 和 Ser GSK-3β。在这些肌肉中，母体 VDD 导致 1,25-二羟维生素 D3（calcitriol）（两倍；P<0.05）和 CYP27B1（58%；P<0.05）的含量代偿性增加，CYP27B1 是一种将骨化二醇转化为 1,25-二羟维生素 D3 的代谢酶。有趣的是，M-VDD 雄性后代的慢肌（比目鱼肌）以及雌性后代的 EDL 和比目鱼肌中均未观察到 EDL 中的大多数形态和生化变化。
这些数据表明，母体 VDD 选择性地影响雄性后代大鼠 II 型肌肉纤维的发育，但不影响雌性后代大鼠，并且提示快肌（EDL）中 Vit. D 含量的代偿性增加可能导致其大小和抗疲劳能力的增强。
