Health Consequences of Circadian Disruption in Humans and Animal Models - Progress in Molecular Biology and Translational Science - page 296

mice and 9/18 in delaying mice. 310 However, LD inversions every 3-4 days
provided to pregnant rats did not compromise reproductive success despite
the appearance of glucose intolerance and insulin resistance in adult off-
spring. 199 In contrast, exposure to constant light and non-24 h LD cycles
(12 h) in rats reduced fertility and preterm fetus body weight. 311 Higher
levels of embryonic reabsorption and pup mortality after birth are also evi-
dent in mice housed under non-24 h LD cycles (22 and 26 h). 312 Environ-
mental circadian disruption also compromises reproduction in flies, with
restricted food access to the typically inactive phase of the LD cycle causing
female flies to produce fewer eggs. 313

4.5.2 Genetic models
Clock gene rhythms are evident in a variety of central and peripheral repro-
ductive tissues, 277,302 and proper temporal coordination within and between
tissues is thought to be important for reproductive viability. Consistent with
this view, homozygous clock mutant mice display poor reproductive success,
longer and irregular estrous cycles, and an undetectable luteinizing hormone
surge at the appropriate phase. 314-319 Irregular estrous cycles were further
exacerbated when clock mutant mice were arrhythmic after release into con-
stant darkness. 318 Furthermore, of the mice that successfully mated, clock
mutant mice displayed higher rates of abnormalities during pregnancy,
including reabsorption of embryos and fully formed fetuses, along with dif-
ficulties during labor under an LD cycle 317 or constant darkness. 318 How-
ever, these effects appear to be influenced by strain, with more severe
effects observed with the clock mutation on the B6 than on the Balb/c back-
ground. 319 Some conflicting results have also been obtained with the

bmal1 mouse model. While initial reports did not indicate the presence

of reproductive defects, 61,320 subsequent studies report that bmal1

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mice
display irregular estrous cycles and impaired fertility. 321-323 Female mice lac-
king per1 or per2 also display irregular estrous cycles and reduced fertility
during middle age (9-12 months of age) despite fecundity comparable to
wild type mice at 2-6 months of age. 324 While there is little work investi-
gating potential associations between reproductive complications and clock
gene polymorphisms in humans, one study reported a relationship between
bmal1 and npas2 variants and miscarriage. 325

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4.6. Mood disorders
Close links between circadian regulation and mood can be inferred from the
fact that many psychological disorders are characterized by sleep and