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

Colin Timaxian,Linda Gulliver,Anne Guillou,Karl Balabanian,Karim Chébli,Isabelle Raymond-Letron,Céline Bouclier,Ludovic Le Corre,Patrice Mollard,Gwendal Lazennec

doi:10.26508/lsa.201900599

Abstract

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.

Highlights

Bystander chronic infections are common in rodent animal conventional facilities with a high prevalence of viruses such as mouse norovirus, parvovirus, mouse hepatitis virus, rotavirus, and bacteria such as helicobacter (Pritchett-Corning et al, 2009)
Cxcr2 KO females of conventional conditions exhibited a smaller weight than WT animals (Fig 1D), which was not the case in Specific and Opportunistic Pathogen-Free (SOPF) conditions (Fig 1C)
We investigated the effects of bystander infections on the physiologic role of the chemokine receptor Cxcr2 using Cxcr2

Summary

Introduction

Bystander chronic infections are common in rodent animal conventional facilities with a high prevalence of viruses such as mouse norovirus, parvovirus, mouse hepatitis virus, rotavirus, and bacteria such as helicobacter (Pritchett-Corning et al, 2009). There is quite a debate about using pathogen-free mice as animal models because several reports have shown that mice exposed to bystander infections better recapitulate the human immune situation than mice housed in pathogen-free conditions (Beura et al, 2016) and that infections can affect the response to vaccination (Reese et al, 2016). It has been shown that transplanting C57BL/6 embryos into domestic wild-type mice trapped in horse stables better recapitulate human immune response than laboratory animals, reinforcing the importance of microbiota (Rosshart et al, 2019). Such pathogen-free influences could account for some of the difficulties in translating animal studies into treatments for patients. Infections are transmitted through different generations of animals, in particular during birth, and during co-housing and breast feeding (McCafferty et al, 2013)

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