Circadian Rhythms & Pregnancy

What are circadian rhythms?

Twenty-four-hour biological cycles that align physiology (metabolism, immunity, activity) with day/night.

Which brain region controls mammalian circadian rhythms?

The suprachiasmatic nucleus (SCN) of the anterior hypothalamus.

What are zeitgebers and give examples?

External cues that entrain circadian rhythms; examples: light (strongest), food, temperature.

Which retinal cells detect light for circadian entrainment?

Retinal ganglion cells that project to the SCN.

Name the core clock genes.

Clock, Bmal1, Per1–3, Cry1–2, Rev-erbα, Rorα.

Describe the CLOCK:BMAL1 → PER/CRY feedback loop.

CLOCK and BMAL1 drive Per/Cry expression; PER/CRY proteins inhibit CLOCK/BMAL1, creating a transcriptional-translational feedback loop.

What stabilises the core clock gene loop?

Rev-erbα (suppresses Bmal1) and Rorα (activates Bmal1).

What percentage of cellular genes are under circadian control?

About 20–25% of expressed genes.

Which systems are affected by clock genes?

Metabolism, immune system, cardiovascular function, kidney output, fat storage/mobilisation, reproduction.

Example of phenotype from Clock deletion?

Hyperphagia and metabolic syndrome.

Example of phenotype from Bmal1 deletion?

Alters carbohydrate metabolism and reproduction.

Example of phenotype from Cry1/2 deletion?

Causes inflammatory phenotype.

How do circadian rhythms change across the day in humans?

Morning: ↑ blood pressure & glucocorticoids. Afternoon: peak coordination & reaction time. Evening: ↑ body temp. Night: ↑ melatonin, ↓ metabolism.

What are maternal cardiovascular adaptations to pregnancy?

↑ Cardiac output (~40%), ↑ plasma volume (~40%), ↓ vascular resistance.

What are maternal respiratory adaptations to pregnancy?

↑ Tidal volume (~40%), ↑ maternal oxygen consumption (~15%).

How do circadian glucocorticoid rhythms change in pregnancy?

Rhythm maintained but absolute levels increase late gestation, aiding fetal organ maturation.

Do rat placentas express clock genes?

Yes, but rhythms are weak/non-robust, likely driven by maternal signals.

Do human placentas express clock genes?

Yes, with rhythmicity and anti-phase patterns, suggesting intrinsic rhythmicity plus maternal signals.

How does pregnancy alter maternal liver clock gene expression?

Early: amplification (e.g., Per3). Late: suppression of Bmal1, Per1/2, Cry1/2.

What are the two phases of maternal metabolic adaptation?

Phase 1: anabolic (storage). Phase 2: catabolic (mobilisation to fetus).

What experimental methods were used to study circadian genes in pregnancy?

RT-qPCR of clock and nutrient transporter genes across Zeitgeber times; cosinor analysis.

What is “mesor” in circadian analysis?

The mean level of rhythmic expression across the day.

What is “amplitude” in circadian analysis?

Difference between peak and trough of rhythmic expression.

What is “acrophase” in circadian analysis?

Timing of the peak of rhythmic expression.

How did shift-work models affect rodent pregnancy?

Disrupted food intake, hormone profiles, clock gene expression, and metabolism.

What are maternal risks of shift work during pregnancy?

↑ Preterm birth, low birthweight, spontaneous abortion.

What are offspring risks of maternal circadian disruption?

Altered body composition, glucose intolerance, lipid metabolism changes, ↑ risk of obesity/adult disease.

How does circadian rhythmicity help fetal development?

Maternal and placental signals may entrain the developing fetal circadian system.

Why is circadian hygiene important in pregnancy?

Supports maternal health, placental function, and optimal fetal outcomes.

Why use animal models for circadian rhythms in pregnancy?

Short gestation, controlled environment, multi-tissue sampling; but extrapolation to humans needed.

How does placental rhythmicity differ between rats and humans?

Rats: weak/non-robust, maternal-driven. Humans: clear anti-phase rhythmicity, stronger intrinsic rhythms.

Why is anti-phase expression (Bmal1 vs Per/Cry) important?

Indicates robust circadian feedback loop; absence = weak rhythms.

Why measure at multiple Zeitgeber times (ZT1, 7, 13, 19)?

Captures daily rhythmic changes; single timepoint may miss peaks/troughs.

What is the advantage of cosinor analysis?

Quantifies mesor, amplitude, acrophase statistically.

What hypothesis was made about adipose tissue clock genes in pregnancy?

Early: suppression (like high-fat diet). Late: upregulation for mobilisation.

What hypothesis was made about liver clock genes in pregnancy?

Early: upregulation. Late: suppression of Bmal1, Per1/2, Cry1/2.

What experimental finding in maternal liver supported this?

Per3 rhythm amplified early, suppressed late, consistent with predictions.

How do late-pregnancy glucocorticoids affect fetal development?

Drive fetal organ maturation, link maternal SCN to peripheral/fetal tissues.

Why might circadian disruption cause low birth weight/preterm birth?

Disrupted maternal hormones impair placental-fetal communication and growth regulation.

How does circadian disruption predispose offspring to adult disease?

Alters fetal programming of glucose/lipid metabolism → ↑ obesity, insulin resistance.

Why are maternal and placental rhythms critical for fetal circadian maturation?

Fetus lacks strong intrinsic rhythms early; relies on maternal/placental cues.

How can this research inform public health recommendations?

Supports circadian hygiene in pregnancy; guides shift work policy and maternal care.

What do peripheral clocks in tissues imply for pregnancy adaptation?

Organs adjust rhythms for storage vs mobilisation, coordinated by SCN/placental signals.

If placental rhythmicity is weak, what does this suggest about fetal reliance?

Fetal entrainment depends heavily on maternal cues.

Why is circadian biology in pregnancy clinically important?

Disruption impacts maternal health, pregnancy outcomes, and long-term offspring health.