Researchers discovered that a midgestational elevation in the hormone leptin, which most of us identify with hunger reduction, produces serious blood vessel malfunction and inhibits the baby’s growth in preeclampsia, which puts both mother and baby at danger.
The study’s findings were published in the journal ‘Hypertension.’ Critical supply chain difficulties with nutrition and oxygen can result in preterm delivery or even death, as well as an increase in the child’s and mother’s lifelong risk of cardiovascular disease.
Women with preeclampsia have an increase in leptin production by the placenta at 20 weeks into their pregnancy, but the consequences are unknown.
“It’s sort of emerging as a marker of preeclampsia,” said Dr Jessica Faulkner, a vascular physiologist in the Department of Physiology at the Medical College of Georgia and the study’s corresponding author in the journal Hypertension.
Leptin, which is mostly generated by fat cells, is also created by the placenta, which allows the mother to provide nutrition and oxygen to her developing baby, according to Faulkner.
Leptin levels rise regularly during a healthy pregnancy, although it’s unclear exactly what leptin does in this situation. There is some indication that it is a natural nutrition sensor in reproduction or a means to allow new blood vessel formation and/or activate growth hormone for normal development.
However, leptin levels rise greater in preeclamptic individuals.
“However, in preeclamptic individuals, leptin levels rise more than they should,” Faulkner explained.
The current study indicates for the first time that an increase in leptin causes endothelial dysfunction, which causes blood vessels to tighten, their ability to relax, and the baby’s growth to be inhibited.
When the scientists suppressed the precursor for the potent, natural blood artery dilator nitric oxide, as happens in hypertension, the effect of the midgestation leptin rise was nearly identical.
To make matters worse, the researchers have evidence that leptin increases levels of the blood vessel constrictor endothelin 1.
Endothelial failure did not occur when the aldosterone receptors, in this case the mineralocorticoid receptors on the surface of the cells that line blood arteries, were eliminated, according to Dr Eric Belin de Chantemele, physiologist in MCG’s Vascular Biology Center and the paper’s senior author.
“We believe the placenta is not adequately developed in preeclamptic individuals,” Faulkner explains. “Fetal growth is not progressing as it should in the middle of pregnancy. The placenta, I believe, is compensating by boosting leptin synthesis “Possibly with the purpose of promoting more normal development. However, the consequences appear to be the polar opposite.
“It can harm the baby’s growth and raise the chance of long-term health problems for both the infant and the mother,” she said.
While leptin has been linked to preeclampsia, this is the first study to indicate that as leptin levels rise, the harmful clinical signs of preeclampsia emerge, according to Belin de Chantemele.
They saw an unfavourable chain reaction when they injected leptin into pregnant mice to imitate the spike that occurs in preeclampsia, with the adrenal gland producing more of the steroid hormone aldosterone, which might be enhancing the synthesis of endothelin 1, also by the placenta.
Previous research has revealed that an infusion of leptin causes endothelial dysfunction outside of pregnancy.
Belin de Chantemele’s lab pioneered research demonstrating that fat-derived leptin directly stimulates the adrenal glands to produce more aldosterone, which activates mineralocorticoid receptors found throughout the body, particularly in female blood vessels, and is important for blood pressure levels.
Obesity is characterised by high aldosterone levels, which are a significant cause of metabolic and cardiovascular issues.
They hypothesised that the infusion of leptin at midgestation in preeclampsia had a similar effect that deletion of the mineralocorticoid receptors lining blood vessels may resolve. They’ve linked comparable physiological dots in young girls, where obesity frequently robs the early years of the protection from cardiovascular illness that being female generally confers until menopause.
According to Faulkner, these same players are probable contributors in what raises the mother’s lifetime risk of cardiovascular issues.
“It suggests the system is dysregulated, and that’s when you get the sickness,” she explained.
Their aims include better understanding the routes for high blood pressure and other blood vessel malfunction, pathways that may be targeted during pregnancy to avert potentially fatal outcomes for both mother and baby from what Faulkner refers to as a “two-hit disease.”
To date, their findings suggest that current medications like eplerenone, a blood pressure prescription that binds to the mineralocorticoid receptor, thereby lowering the effect of increased levels of aldosterone, might be useful therapy to better protect mother and baby.
The issues most likely begin with the placenta, and maybe insufficient blood supply to the temporary organ early in its development, as well as subsequent failure of the formation of the large blood arteries that become the pathway for nutrition and oxygen from mother to baby.
Preeclampsia is known to cause issues such as reduced release of placental growth hormones. The bottom line appears to be that by midgestation, the placenta can no longer adequately support the baby, which may be why it secretes leptin, possibly to stimulate its own growth and normal foetal development, but in reality, it contributes to cardiovascular and fatal consequences, including raising the mother’s blood pressure, the scientists report.
Growing Preeclampsia cases
“Unfortunately, preeclampsia rates are growing,” Faulkner adds, both in terms of the number of pregnant women affected and the severity with which they are impacted.
According to a CDC data analysis published in the Journal of the American Heart Association in January of this year, rates of hypertension during pregnancy, including preeclampsia and gestational hypertension, nearly doubled in both rural and urban areas of the United States from 2007 to 19 and have been increasing since 2014.
Gestational hypertension is defined as a rise in a pregnant woman’s blood pressure during the third trimester but without the presence of protein in the urine, a symptom of renal distress, or indicators of placental malfunction present in preeclampsia.
Carrying more than one foetus, persistent high blood pressure, type 1 or 2 diabetes, renal illness, autoimmune problems before pregnancy, and the use of in vitro fertilisation are also risk factors.
Obesity, which is a risk factor for several of these illnesses and is related with high levels of both aldosterone and leptin, is mostly to blame for rising incidence of preeclampsia, according to Faulkner. Other times, women appear to acquire the condition on their own.
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