Endocrine and Paracrine Regulation of Birth at Term and Preterm

Abstract

We have examined factors concerned with the maintenance of uterine quiescence during pregnancy and the onset of uterine activity at term in an animal model, the sheep, and in primate species. We suggest that in both species the fetus exerts a critical role in the processes leading to birth, and that activation of the fetal hypothalamic-pituitary-adrenal axis is a central mechanism by which the fetal influence on gestation length is exerted. Increased cortisol output from the fetal adrenal gland is a common characteristic across animal species. In primates, there is, in addition, increased output of estrogen precursor from the adrenal in late gestation. The end result, however, in primates and in sheep is similar: an increase in estrogen production from the placenta and intrauterine tissues. We have revised the pathway by which endocrine events associated with parturition in the sheep come about and suggest that fetal cortisol directly affects placental PGHS expression. In human pregnancy we suggest that cortisol increases PGHS expression, activity, and PG output in human fetal membranes in a similar manner. Simultaneously, cortisol contributes to decreases in PG metabolism and to a feed-forward loop involving elevation of CRH production from intrauterine tissues. In human pregnancy, there is no systemic withdrawal of progesterone in late gestation. We have argued that high circulating progesterone concentrations are required to effect regionalization of uterine activity, with predominantly relaxation in the lower uterine segment, allowing contractions in the fundal region to precipitate delivery. This new information, arising from basic and clinical studies, should further the development of new methods of diagnosing the patient at risk of preterm labor, and the use of scientifically based strategies specifically for the management of this condition, which will improve the health of the newborn.

Prenatal loss of father during World War One is predictive of a reduced lifespan in adulthood

“…Placental 11β-HSD2 is more active in females (44) and is sensitive to maternal stress, which causes a greater transfer of glucocorticoids from mother to fetus. A reduction in placental levels of 11β-HSD2 occurs during late gestation, allowing an increased transfer of maternal glucocorticoids to the fetus and exacerbation of the effects of maternal stress on the fetus (45,46). Because maternal cortisol levels are much higher than fetal levels, even moderate changes in placental 11β-HSD2 can significantly modify the glucocorticoid exposure of the fetus.…”

Vaginal Misoprostol vs Vaginal Misoprostol With Estradiol for Labor Induction: A Prospective Double Blind Study

“…These EP receptor labor-associated alterations suggest that EP receptor expression is hormonally regulated at the time of labor, by the changes in progesterone and estrogens associated with parturition [4].…”

Effects of periconceptional undernutrition on the initiation of parturition in sheep

“…Despite the existence of a functional negative feedback mechanism in the fetal HPAA at 121-131 days gestation, plasma adrenocorticotrophin (ACTH) and cortisol concentrations rise progressively in a semilogarithmic pattern in the last 15-20 days of gestation (14,(32)(33)(34). This sustained release of glucocorticoids is essential for organ maturation and also provides the trigger for the initiation of parturition (7).…”