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New way to reduce long-term complications in preterm infants

New avenues to reduce long-term complications in preterm infants
Some GnRH neurons (green) express NOS1 (red) during migration from the nose to the brain ) during fetal life. GnRH + NOS1 double labeled cells are shown in yellow. Credit: Vincent Prevot/Inserm

Children born prematurely are at higher risk for cognitive and sensory impairments, as well as infertility in adulthood. In a new study, a team of researchers from the University of Lille from Inserm, the University Hospital of Lille and the Laboratory of Neuroscience and Cognition at the University of Lille has opened up interesting avenues for improving outcomes.

By studying a rare disease called congenital hypogonadism, scientists have discovered a The key role played by this enzyme, its synthesis of the neurotransmitter nitric oxide, has therapeutic potential in reducing the risk of long-term complications in preterm birth. Their findings are described in Science Translational Medicine . Lille University Hospital is also conducting a clinical trial in collaboration with a hospital in Athens (Greece) to further measure the effects of nitric oxide on premature infants.

Congenital hypogonadotropic hypogonadism is a rare disorder characterized by delayed or complete puberty There is no puberty, leading to infertility. Some forms of the disease are caused by a lack of production of GnRH, a hormone produced in the brain that remotely controls male and female gonad development and function through various mediators.

Inserm Research Director Vincent Prévot and his team study the brain and other dialogue between parts. Here, the scientists studied nitric oxide, a neurotransmitter that regulates GnRH neuron activity, and more specifically NOS1, the enzyme that synthesizes it. “Nitric oxide inhibits the electrical activity of GnRH neurons and regulates the release of this hormone, so NOS1 dysfunction cannot be ruled out as a cause of congenital gonadotropin hypogonadism,” explains Prévot, lead coordinator of the study.

To go one step further, his team collaborated with a laboratory in Lausanne (Switzerland), which has 341 patients patients with this disease. The researchers used DNA samples to look for rare mutations in the gene encoding the NOS1 enzyme and found five different mutations that could explain the disease. In addition to fertility problems, some people show sensory and cognitive impairment (intellectual disability or hearing or smell loss).

Application in the case of premature birth? Research The next stage involves developing NOS1-deficient mouse models to better understand the role of this enzyme. The researchers identified puberty problems in the animals, as well as sensory and neurological changes, observed in humans with congenital hypogonadotropic hypogonadism.

They also saw worsening puberty in these animals. All mammals experience small puberty right after birth (1 to 3 months of age in humans) and trigger initial brain activation that controls the reproductive axis before the “true” puberty of puberty.

Here, the researchers observed sex hormone spikes associated with this small puberty in NOS1-deficient mice twice as much. “This caught our attention because preterm infants also tend to exhibit more intense puberty than usual. And the more preterm birth, the greater the risk of neurosensory and psychiatric complications in adulthood,” said Inserm researchers and the study’s No. According to one author Konstantina Chachlaki.

Based on these observations, the researchers tested a NOS1-deficient mouse after birth Administration of nitric oxide. small adolescence. What they saw was a reversal of all the symptoms they had experienced: puberty problems and sensory and neurological impairments disappeared. In the long run, it’s the rest of their lives.

Initiate clinical trial

These promising findings may improve the care of preterm infants. Some premature babies already use nitric oxide to open up the bronchi when breathing is difficult.

“In view of this consistency of observation and practice, we decided to establish a clinical trial to investigate reproductive and neurosensory parameters to test the effect of nitric oxide on preterm infants,” explains Vincent Prévot and Konstantina Chachlaki, coordinators of minNO European. This project is dedicated to studying the role of small adolescence in premature infants.

“Nitric oxide at birth may reduce the risk of reproductive, sensory and intellectual complications in premature infants. This is what we Validation will be attempted after these surprising findings in mice.”

miniNO trial launched at University Hospital Lille and Athens (Greece ) with a hospital. The aim was to verify whether children who received this treatment continued to experience normal small puberty and puberty, and whether they experienced fewer sensory and neurological complications than preterm infants who were not given nitric oxide at birth. The clinical trial was designed to include 120 patients at two sites (Athens and Lille) over a 24-month period.

More information: Konstantina Chachlaki et al, NOS1 mutation causes hypogonadotropic hypogonadism with sensory and cognitive deficits that is reversible in infant mice, Science Translational Medicine

(2022). DOI: 10.1126/scitranslmed.abh2369. www.science.org/doi/10.1126/scitranslmed.abh2369
: Reducing long-term complications in preterm infants New Pathways (Oct. 5, 2022), retrieved Oct. 19, 2022 from https://medicalxpress.com/news/2022-10-avenues-long-term-complications-preterm-infants.html

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