Health Consequences of Circadian Disruption in Humans and Animal Models - Progress in Molecular Biology and Translational Science - page 295

evident under 22 h LD cycles, which suggests that the pathology is caused by
the altered alignment to the external lighting condition and not the genetic
mutation itself. Furthermore, pathology was not evident in SCN-lesioned
hamsters, suggesting that no clock is better than a misaligned clock. Pathology
was not evident in homozygote taumutant hamsters, perhaps due to their free-
running state under 24 h LD cycles. As further support for circadian disruption
being associated with cardiovascular disease, recent work demonstrates that
bmal1

mice display cardiomyopathy, endothelial dysfunction, and arterio-
sclerosis. 208,268-273 While bmal1

/

mice display a variety of pathologies
that could contribute to cardiovascular dysfunction, the hypothesis that
the circadian clock per se is required for cardiovascular health is supported
by results obtained in other clock gene models. 207,224,268,271,273-275 Similar
to metabolic syndrome, there is some evidence linking clock gene polymor-
phisms in humans with an increased risk for cardiovascular disease ( bmal1

/

229

276

and clock ).

4.5. Reproduction issues
Reproductive cycles are regulated by circadian clocks, and reproductive
function serves as a useful indicator of disease states that would limit the abil-
ity to support pregnancy and lactation. 277 Relative to day workers, rotating
and night shift workers display a higher risk for a number of reproductive
issues, including irregular menstrual cycles, endometriosis, preterm births,
spontaneous abortions, and low birth weight. 278-300

4.5.1 Environmental models
In rodents, the circadian system regulates the timing of reproduction so that it
occurs at optimal times of the day and year (reviewed in Ref. 301 ) , and the
timing of behavioral and physiological reproductive events can be altered and
disrupted by environmental stimuli that adjust the circadian phase. 302-304
Non-24 h schedules in rats produces a lower amplitude surge in luteinizing
hormone likely due to lower phase coherence between SCN compart-
ments. 305 Likewise, hamsters with bimodal activity rhythms under constant
light display two daily surges in luteinizing hormone with lower amplitude
peaks, presumably due to antiphase cycling of the bilateral SCN lobes. 306
Furthermore, constant light in rodents disrupts estrous cycles 307,308 and
inhibits male reproductive function in South Indian gerbils. 309 Repeated
6 h phase advances of the LD cycle applied every 5 days after copulation
severely compromised pregnancy outcomes in mice, with normal term
births successful in 11/12 control mice compared to only 4/18 in advancing