Cortisol Regeneration in the Fetal Membranes, A Coincidental or Requisite Event in Human Parturition?

The fetal membranes are equipped with high capacity of cortisol regeneration through the reductase activity of 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1). The expression of 11ß-HSD1 in the fetal membranes is under the feedforward induction by cortisol, which is potentiated by proinflammatory cytokines. As a result, the abundance of 11ß-HSD1 increases with gestational age and furthermore at parturition with an escalation of cortisol concentration in the fetal membranes. Accumulated cortisol takes parts in a number of crucial events pertinent to the onset of labor in the fetal membranes, including extracellular matrix (ECM) remodeling and stimulation of prostaglandin output. Cortisol remodels the ECM through multiple approaches including induction of collagen I, III, and IV degradation, as well as inhibition of their cross-linking. These effects of cortisol are executed through activation of the autophagy, proteasome, and matrix metalloprotease 7 pathways, as well as inhibition of the expression of cross-linking enzyme lysyl oxidase in mesenchymal cells of the membranes. With regard to prostaglandin output, cortisol not only increases prostaglandin E2 and F2α syntheses through induction of their synthesizing enzymes such as cytosolic phospholipase A2, cyclooxygenase 2, and carbonyl reductase 1 in the amnion, but also decreases their degradation through inhibition of their metabolizing enzyme 15-hydroxyprostaglandin dehydrogenase in the chorion. Taking all together, data accumulated so far denote that the feedforward cortisol regeneration by 11ß-HSD1 in the fetal membranes is a requisite event in the onset of parturition, and the effects of cortisol on prostaglandin synthesis and ECM remodeling may be enhanced by proinflammatory cytokines in chorioamnionitis.

Preterm Birth in China Between 2015 and 2016.

Objectives. To describe the incidence, risk factors, and potential causes of preterm birth (PTB) in China between 2015 and 2016.Methods. The China Labor and Delivery Survey was a population-based multicenter study conducted from 2015 to 2016. We assigned each birth a weight based on the sampling frame. We calculated the incidence of PTB and the multivariable logistic regression, and we used 2-step cluster analysis to examine the relationships between PTB and maternal, fetal, and placental conditions.Results. The weighted nationwide incidence of PTB was 7.3% of all births and 6.7% of live births at 24 or more weeks of gestation. Of the PTBs, 70.5% were born after 34 weeks and 42.7% were iatrogenic. Nearly two thirds of all preterm births were attributable to maternal, fetal, or placental conditions, and one third had unknown etiology.Conclusions. This study provided information on the incidence of PTB in China and identified several factors associated with PTB. The high frequency of iatrogenic PTB calls for a careful assessment and prudent management of such pregnancies, as PTB has short- and long-term health consequences.

[The three mechanisms underlying progesterone withdrawal in late pregnancy in mammals].

Endocrine hormones are important factors in maintaining pregnancy as well as initiation of parturition. Progesterone is the major hormone maintaining myometrium quiescence, while glucocorticoids, prostaglandins and estrogen are among the major hormones involved in the initiation of parturition. Therefore progesterone withdrawal at the end of pregnancy is the prerequisite for the initiation of parturition. However, unlike most of the other species of mammals that the withdrawal of progesterone is achieved via reduction of progesterone synthesis or increased conversion of progesterone to estrogen, some mammals including the primates maintain high progesterone level throughout gestation and even during parturition. Accumulating lines of evidence indicate that the withdrawal of progesterone in human being is attained via the changes of the expression ratio of progesterone receptor subtypes and the changes of co-activators required for the activation of transcriptional activity of progesterone receptor. Here we reviewed the three major mechanisms, namely luteolysis, upregulation of placental P450c17 hydroxylase and changes of progesterone receptor functions, underlying progesterone withdrawal in late pregnancy in mammals.