Mini-puberty is a developmental stage that occurs in all mammals, including us, shortly after birth. It is necessary for brain maturation and subsequent fertility. Its development had already been described in female mice, and the work of a team Inserm from the University Hospital of Lille, taken to the male, complete the picture today. Ultimately, this knowledge could help fight against disorders that occur in premature children who present abnormal mini-puberty.
At the Lille University Hospital, researchers hope to improve the prognosis of children born prematurely, who present an increased risk of sensory, cognitive or even metabolic disorders in adulthood. Previous work they have carried out in animals has shown a correlation between the risk of developing these disorders and the occurrence of abnormal mini-puberty. By studying this association, the scientists discovered the major involvement of nitric oxide (NO), a molecule produced in the brain by specialized neurons. ” NO regulates the activity of other neurons that produce a hormone called GnRH (for Gonadotropin Releasing Hormone) and orchestrate the establishment and regulation of reproductive function. When the activity of NO neurons is suppressed in mice, mini-puberty is abnormal, the animals are infertile and also develop a procession of sensory and mental disorders similar to those observed in certain people born prematurely. “, explains Konstantina Chachlaki, Inserm researcher in the Neuroscience and Cognition laboratory of the Lille University Hospital. To hope to prevent the onset of these developmental disorders, researchers must begin by understanding how mini-puberty works and the role played by the neurons that produce NO. They carry out this work within the framework of the international research program miniNO coordinated by Vincent Prévot and Konstantina Chachlaki.
Mini-puberty, what is it?
Mammalian mini-puberty occurs right after birth. It is necessary for the subsequent acquisition of fertility and plays a role in the maturation of the brain. It corresponds to a phase of temporary activation of the axis that connects the brain and the genitals (the gonadotropic axis). GnRH neurons that orchestrate the initiation and regulation of reproduction in the brain are temporarily activated, leading to early hormone production LH et FSH responsible for the functioning of the gonads (ovaries and testicles). The system goes out quickly, and it is necessary to await the true puberty, with adolescence, to attend its awakening.
The team has previously described the course of mini-puberty in female mice, but data was lacking in males. A gap that Virginia Delli set out to fill in the context of her doctorate, carried out under the supervision of Konstantina Chachlaki. This work has highlighted several differences between animals of both sexes. In males, peak production of the FSH hormone occurs 23 days after birth, while it occurs a week earlier in females. A LH surge is then observed, 30 days after the FSH level has returned to its basal level, marking a two-phase mini-puberty. About hormones steroids, the testosterone level remains low in males throughout mini-puberty, while that of estrogen is on the contrary high, as in females. But the origin of these estrogenwhich will activate the neurons to NO, varies according to the sexes: “ In the female these hormones come from the ovaries, while in the male they do not come from the testicles but from other tissues which also produce estrogen, such as the adipose tissuebones or skin “, explains Konstantina Chachlaki.
Finally, the use of genetically modified male mice has enabled the researchers to show that the absence of NO upsets this mechanism: the FSH peak is weaker and that of LH is earlier. This results in a dysfunction in the production of sex hormones, with in particular a deficiency in testosterone and estrogen which impacts the activation of neurons at NO, with perhaps the key to problems of maturation of the brain which would explain the anomalies of development. later.
An ongoing clinical trial
While waiting to continue to decipher these mechanisms which seem to link prematurity and developmental disorders, Konstantina Chachlaki has helped launch a clinical trial to find out whether premature infants who received NO at birth in order to facilitate the opening of their bronchi (a common practice) exhibit normal mini-puberty and less later developmental impairment than those who did not receive it. If this is the case, the care of these children could evolve, even before biology has shed all the light on these anomalies.
Konstantina Chachlaki is a researcher in the Development and Plasticity of the Neuroendocrine Brain team led by Vincent Prévot, in the Lille Neuroscience and Cognition research unit (unit 1172 Inserm/University of Lille/CHU of Lille).
Source : V. Delli et al. Male minipuberty involves the gonad-independent activation of preoptic nNOS neurons. Free Radical Biology and Medicine, online edition December 5, 2022. doi: 10.1016/j.freeradbiomed.2022.11.040
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![[2016-01-15] INFRv4_infertility, unpublished_IAU.jpg](https://www.inserm.fr/wp-content/uploads/media/entity_images/2016-01-15-infrv4-infertilite-inedit-iau.jpg)
Source: www.inserm.fr
