Maternal vitamin D deficiency affects the morphology and function of glycolytic muscle in adult offspring rats

J Cachexia Sarcopenia Muscle. 2022 Aug;13(4):2175-2187. doi: 10.1002/jcsm.12986. Epub 2022 May 18.

Abstract

Background: 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.

Methods: 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.

Results: 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 473 Akt and Ser 21/9 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.

Conclusions: 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.

Keywords: Fetal programming; Hypertrophy; Muscle development; Skeletal muscle; Vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitriol / analysis
  • Calcitriol / metabolism
  • Calcitriol / pharmacology
  • Female
  • Glycogen Synthase Kinase 3 beta / analysis
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Glycogen Synthase Kinase 3 beta / pharmacology
  • Male
  • Muscle Fibers, Fast-Twitch / physiology
  • Muscle Fibers, Slow-Twitch* / physiology
  • Muscle, Skeletal / metabolism
  • Rats
  • Rats, Wistar
  • Vitamin D Deficiency* / complications
  • Vitamin D Deficiency* / metabolism

Substances

  • Glycogen Synthase Kinase 3 beta
  • Calcitriol