Changes of Placental Kiss-1 mRNA Expression and Maternal/Cord Kisspeptin Levels at Preterm Delivery

Abstract

Kisspeptin, a placental polypeptide secreted throughout pregnancy, is suggested to play a role at parturition. Here we evaluated whether its placental mRNA expression and maternal/fetal plasma levels change at term and preterm delivery, and its effect on oxytocin secretion from placental explants. Samples were collected from 40 women with singleton pregnancies who underwent elective cesarean section at term (TNL), term vaginal delivery (TD), and preterm vaginal delivery (PTD). Plasma Kisspeptin and oxytocin levels were assessed by ELISA; placental mRNA expression by Real-time quantitative RT-PCR analysis. Placental expression was significantly (P < 0.0001) higher in PTD than TNL and TD and significantly (P < 0.001) higher in TD than TNL. Maternal/fetal plasma concentrations did not differ among the groups, and maternal were significantly higher than fetal levels (P < 0.05). In placental explants increasing doses of kisspeptin did not modify oxytocin secretion. In conclusion, labor is associated with increased placental KiSS-1 expression without changes in maternal/fetal circulation.

DNA methylation profiling of human placentas reveals promoter hypomethylation of multiple genes in early-onset preeclampsia

“…Although DNA methylation at critical sites can reflect the availability of a gene for transcription, which may lead to altered expression depending on other regulatory factors present, it has a number of advantages over expression studies. First, it may be more resistant to the transient changes in gene expression associated with labor and delivery, [12][13][14] as well as the effects of placental storage before sample processing. 15 Although we did in this case observe an inverse association between TIMP3 methylation and expression, expression studies at term may not always reflect that which occurred during relevant periods of development.…”

“…[9][10][11] However, many factors may cause short-lived temporal changes in gene expression [12][13][14] and, furthermore, placental RNA can degrade during parturition and rapidly after delivery of the placenta, 15 making it difficult to obtain useful samples. DNA methylation is generally more stable and provides an alternative marker for underlying processes in the cell.…”

Potential Clinical Use of Kisspeptin

“…Most found that women with early bleeding in pregnancy [60], recurrent spontaneous abortion [61,62], metabolic conditions including diabetes and hypertension during pregnancy [63], development of pre-eclampsia, and intra-uterine growth restriction [64,65,66] had lower levels of circulating kisspeptin and decreased levels of kisspeptin receptor on placental immunohistochemistry. However, others found no difference in circulating levels of kisspeptin [67] and/or higher levels of placental expression of kisspeptin receptor at the time of pre-term labour [68]. A recent study by Calder et al [69], however, showed that in a transgenic mouse model, intact uterine kisspeptin signalling was essential for successful implantation of the embryo.…”

Organizational and activational effects of sex steroids on kisspeptin neuron development

“…Moreover, sparse kisspeptin immunoreactivity or weak Kiss1 hybridization has sometimes been detected in the bed nucleus of the stria terminalis (BNST), dorsal-medial hypothalamus, ventromedial hypothalamus, and brain stem, though whether this staining represents true kisspeptin populations is contentious and remains to be validated [11; 17; 20; 156]. While kisspeptin is generally thought of as a neuropeptide, it is also found in a variety of non-neural tissues, including the placenta, pancreas, gonads, pituitary, and adipose tissue [14; 15; 77; 103; 146; 148], but very little is known about the function or regulation of these non-neural populations.…”