A placental clock controlling the length of human pregnancy

  title={A placental clock controlling the length of human pregnancy},
  author={Mark Mclean and Andrew M. Bisits and Joanne Davies and Russell J. Woods and Philip J. Lowry and Roger Smith},
  journal={Nature Medicine},
We report the existence of a ‘placental clock’, which is active from an early stage in human pregnancy and determines the length of gestation and the timing of parturition and delivery. Using a prospective, longitudinal cohort study of 485 pregnant women we have demonstrated that placental secretion of corticotropin-releasing hormone (CRH) is a marker of this process and that measurement of the maternal plasma CRH concentration as early as 16–20 weeks of gestation identifies groups of women who… 

The placental clock

Placental corticotropin-releasing hormone (CRH), spontaneous preterm birth, and fetal growth restriction: a prospective investigation.

Corticotrophin releasing hormone and the timing of birth.

Clinically, maternal plasma CRH concentrations may be useful in identifying women at high risk of preterm delivery and CRH antagonists may be helpful in preventing preterm labour.

The utility of plasma CRH as a predictor of preterm delivery.

A single measurement of plasma CRH, toward the end of the second trimester, may identify a group at risk for preterm delivery, but over 50% of such deliveries will be unpredicted.

Placental hormones and identification of pregnancy at risk

  • M. TorricelliF. Petraglia
  • Medicine, Biology
    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
  • 2010
Maternal plasma levels of CRH are significantly elevated as early as 18–20 weeks’ gestation in women who subsequently delivered preterm, and controlled studies focusing on the value of second-trimester CRH levels in predicting preterm birth are focused on.

Low Levels of Corticotropin-Releasing Hormone during Early Pregnancy Are Associated with Precocious Maturation of the Human Fetus

It is suggested that exposure to low levels of pCRH early in gestation may be optimal and associated with a response pattern indicating greater maturity, and not necessarily associated with an increased risk for preterm delivery.

Corticotrophin‐releasing Hormone and Fetal Responses in Human Pregnancy

The impaired fetal responses to novelty and increased arousal observed in this study suggest that neurological systems may be targets for placental CRH during sensitive developmental periods.

Clinical use of placental hormones in pregnancymanagement

While few placental hormones have sufficient sensitivity for clinical application, there are promising new biochemical and biophysical markers that, if used in combination, may provide a valid screening tool.



Immunoreactive corticotropin-releasing hormone in human plasma during pregnancy, labor, and delivery.

We previously reported that immunoreactive corticotropin-releasing hormone (CRH) is present in human placenta and third trimester maternal plasma, and that such material is very similar to rat CRH

Corticotropin releasing hormone-binding protein (CRH-BP): plasma levels decrease during the third trimester of normal human pregnancy.

There is an increase in the availability of free, potentially bioactive CRH at term to stimulate the release of ACTH from the maternal pituitary and/or to act at a peripheral, non-pituitary CRH receptor(s).

The placenta, prostaglandins and parturition: a review.

  • G. Thorburn
  • Medicine
    Reproduction, fertility, and development
  • 1991
It is speculated that the growth pattern of the fetus represents a genetically programmed 'clock' which acts by stimulating placental PGE2 production leading to maturation of key organ systems in the fetus and finally parturition.

The identification of a human myometrial corticotropin-releasing hormone receptor that increases in affinity during pregnancy.

This work searched for specific CRH-binding sites in myometrial tissue obtained at biopsy from pregnant (cesarian section) and nonpregnant (hysterectomy) patients and found a single, specific, homogenous, high affinity population of CRH receptors in both tissues.

Steroids modulate corticotropin-releasing hormone production in human fetal membranes and placenta.

It is concluded that immuno- and biologically active CRH is produced not only in the human placenta, but also in the fetal membranes, raising the possibility of a regulatory system similar to that of the hypothalamic pituitary axis, but residing within the placentA and fetal membranes.

Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition.

There was, therefore, no correlation between plasma cortisol and CRH, implying that this placental CRH is not primarily involved in the control of the maternal hypothalamo-pituitary adrenal axis during pregnancy.

Corticotropin-releasing hormone in baboon pregnancy.

It is indicated that gestational changes in CRH-IR in the baboon are different from those observed in humans, and there is a dissociation between maternal plasma CRH and cortisol.

Association of human corticotropin-releasing hormone to its binding protein in blood may trigger clearance of the complex.

It is suggested that the rising levels of CRH are responsible for the reduction in CRH-BP concentrations observed in late pregnancy, and that this reduction is triggered by the binding of CRh-BP to its ligand.

Plasma corticotrophin‐releasing factor (CRF) in abnormal pregnancy

It is raised the possibility that maternal CRF measurement may be of use as a predictive indicator of certain at‐risk pregnancies and in some patients levels were elevated 11 weeks before the onset of signs or symptoms.