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Life Sci Alliance. 2020 Feb 10;3(3). pii: e201900599. doi: 10.26508/lsa.201900599. Print 2020 Mar.

The health status alters the pituitary function and reproduction of mice in a Cxcr2-dependent manner.

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Centre National de la Recherche Scientifique (CNRS), SYS2DIAG-ALCEDIAG, Cap Delta, Montpellier, France.
CNRS, Groupement de Recherche 3697 "Microenvironment of Tumor Niches," Micronit, France.
Department of Histopathology, National Veterinary School of Toulouse, France and Platform of Experimental and Compared Histopathology, STROMALab, Unité de recherche mixte (UMR) Université Paul Sabatier/CNRS 5223, Etablissement français du sang, Institut national de la santé et de la recherche médicale (Inserm) U1031, Toulouse, France.
University of Otago, Dunedin, New Zealand.
Nutrition et Toxicologie Alimentaire (NUTOX) Laboratory - INSERM Lipides, Nutrition, Cancer UMR 1231 - AgrosupDijon, Dijon, France.
Equipe Metazoan Messenger RNAs Metabolism, Montpellier, France.
Institut de Génomique Fonctionnelle, CNRS, INSERM, University of Montpellier, Montpellier, France.
Université de Paris, Institut de Recherche Saint-Louis, EMiLy, INSERM U1160, Paris, France.
Centre National de la Recherche Scientifique (CNRS), SYS2DIAG-ALCEDIAG, Cap Delta, Montpellier, France


Microbiota and chronic infections can affect not only immune status, but also the overall physiology of animals. Here, we report that chronic infections dramatically modify the phenotype of Cxcr2 KO mice, impairing in particular, their reproduction ability. We show that exposure of Cxcr2 KO females to multiple types of chronic infections prevents their ability to cycle, reduces the development of the mammary gland and alters the morphology of the uterus due to an impairment of ovary function. Mammary gland and ovary transplantation demonstrated that the hormonal contexture was playing a crucial role in this phenomenon. This was further evidenced by alterations to circulating levels of sex steroid and pituitary hormones. By analyzing at the molecular level the mechanisms of pituitary dysfunction, we showed that in the absence of Cxcr2, bystander infections affect leukocyte migration, adhesion, and function, as well as ion transport, synaptic function behavior, and reproduction pathways. Taken together, these data reveal that a chemokine receptor plays a direct role in pituitary function and reproduction in the context of chronic infections.

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