The mammalian circadian clock is tightly controlled by clock genes, which have been shown to regulate up to 20% of the transcriptome in any given tissue. Evidence is accumulating that light-modulation perpetually affects circadian clock performance. In accordance, shift work or chronic jet lag is associated with higher risk of disease later in life, including osteoporosis. In this study, we assessed whether gestational jet lag in mice reduces bone mass postnatally.
During gestation, pregnant mice were randomly subjected to either a constant (CON) 12 h light:12 h dark (LD) cycle or to 8-h advance phases (ADV) or delayed phases (DEL) of the LD cycle every 3 days. Male offspring was on a CON LD cycle from birth until 24 weeks of age. Femoral bone mass was assessed by microcomputed tomography and bone strength by three-point bending.
Offspring from pregnant mice on an ADV regimen showed reduced trabecular and cortical bone mass compared to those undergoing a CON regimen. Especially in the diaphysis, endocortical volume (0.37±0.002 vs 0.45±0.01 mm3; P=0.004), perimeter (4.88±0.03 vs 5.19±0.05 mm; P=0.02) and moment of inertia (0.28±0.001 vs 0.34±0.01 mm4; P=0.014), a proxy for bone strength, were significantly reduced in ADV offspring, whereas cortical thickness was elevated (152.6±1.7 vs 146.5±1.8 mm; P=0.05). This was corroborated by reduced stiffness and work to failure in the ADV offspring, although not reaching significance. In contrast to the ADV mice, none of the parameters for the DEL offspring was different from the CON offspring.
We have provided evidence that advanced gestational jet lag reduces bone mass of male adult offspring, which may reflect reduced bone turnover but could also implicate delayed aging. Alternatively, these mice may have compromised periosteal apposition. The skeletal consequences at the cellular level as well as the epigenetic landscaping caused by the different LD cycles remain to be scrutinised.
14 May 2016 - 17 May 2016