Abstract
BackgroundIt is well established that obesity is associated with dysregulation of the ratio between the two major adipokines leptin and adiponectin. Furthermore, it was recently reported that maternal obesity has a significant impact on placental development. Leptin and adiponectin are present at the fetal-maternal interface and are involved in the development of a functional placenta. However, less is known about leptin and adiponectin’s involvement in the placental alterations described in obese women. Hence, the objective of the present study was to characterize the placental expression and DNA methylation of these two adipokine systems (ligands and receptors) in obese women.ResultsBiopsies were collected from the fetal and maternal sides of third-trimester placenta in obese and non-obese (control) women. In both groups, leptin levels were higher on the fetal side than the maternal side, suggesting that this cytokine has a pivotal role in fetal growth. Secondly, maternal obesity (in the absence of gestational diabetes) was associated with (i) elevated DNA methylation of the leptin promoter on fetal side only, (ii) hypomethylation of the adiponectin promoter on the maternal side only, (iii) significantly low levels of leptin receptor protein (albeit in the absence of differences in mRNA levels and promoter DNA methylation), (iv) significantly low levels of adiponectin receptor 1 mRNA expression on the maternal side only, and (v) elevated DNA methylation of the adiponectin receptor 2 promoter on the maternal side only.ConclusionOur present results showed that maternal obesity is associated with the downregulation of both leptin/adiponectin systems in term placenta, and thus a loss of the beneficial effects of these two adipokines on placental development. Maternal obesity was also associated with epigenetic changes in leptin and adiponectin systems; this highlighted the molecular mechanisms involved in the placenta’s adaptation to a harmful maternal environment.
Highlights
It is well established that obesity is associated with dysregulation of the ratio between the two major adipokines leptin and adiponectin
Association between obesity and leptin/leptin receptor expression levels in human third-trimester placenta We studied the expression of leptin and its membrane receptors on the fetal and maternal sides of human term placenta in the control and obese groups
Our present study focused on leptin and adiponectin—both adipokines mainly involved in energy metabolism and the regulation of insulin sensitivity [14, 15]
Summary
It is well established that obesity is associated with dysregulation of the ratio between the two major adipokines leptin and adiponectin. It has been suggested that obesity predisposes women to a harmful, pro-inflammatory environment generated by excess adipose tissue and impairs placental functions [3] It is well-established that placenta is not just a passive tissue mediating fetal-maternal exchanges; the placenta can modify its capacity to supply nutrients in response to intrinsic factors (e.g., gestational age) and extrinsic factors (e.g., nutritional and other environmental variations) in the prevailing conditions in utero [4]. Excessive accumulation of macrophages and lipids, and high levels of oxidative stress have been observed in placenta sample from obese women These alterations result in (i) the production of pro-inflammatory cytokines (including interleukin-6, tumor necrosis factor, and monocyte chemotactic protein 1) [5], and (ii) the nitration of several proteins [6]. The genome regions are differentially methylated and hydroxymethylated: placental DNA methylation levels were 21% higher in an obese group (relative to a non-obese group), whereas hydroxymethylation levels were 31% lower [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
