Differential regulation of vaginal lipocalins (OBP, MUP) during the estrous cycle of the house mouse

Martina Černá,Romana Stopková,Pavel Stopka,Pavel Talacko,Barbora Kuntová

doi:10.1038/s41598-017-12021-2

Abstract

Female house mice produce pheromone-carrying major urinary proteins (MUPs) in a cycling manner, thus reaching the maximum urinary production just before ovulation. This is thought to occur to advertise the time of ovulation via deposited urine marks. This study aimed to characterize the protein content from the house mouse vaginal flushes to detect putative vaginal-advertising molecules for a direct identification of reproductive states. Here we show that the mouse vaginal discharge contains lipocalins including those from the odorant binding (OBP) and major urinary (MUP) protein families. OBPs were highly expressed but only slightly varied throughout the cycle, whilst several MUPs were differentially abundant. MUP20 or ‘darcin’, was thought to be expressed only by males. However, in females it was significantly up-regulated during estrus similarly as the recently duplicated central/group-B MUPs (sMUP17 and highly expressed sMUP9), which in the mouse urine are male biased. MUPs rise between proestrus and estrus, remain steady throughout metestrus, and are co-expressed with antimicrobial proteins. Thus, we suggest that MUPs and potentially also OBPs are important components of female vaginal advertising of the house mouse.

Highlights

During an estrous cycle, most mammalian females will pass through the four consecutive phases including proestrus, estrus, metestrus, and diestrus (e.g. Mus[1, 2], Apodemus[3], Rattus[4])
A group of lipocalins that may be involved in the transport of chemical signals and potentially in the mouse vaginal advertising are members of the odorant binding protein family (OBPs), because in other mammals, they were detected in their vaginal secretions and/or urine
We aimed to determine the level of correlation between the house mouse estrous cycle and the host regulation and degradation of bacteria to further the understanding of the emergence of complex odour mixtures

Summary

Introduction

Most mammalian females will pass through the four consecutive phases including proestrus, estrus, metestrus, and diestrus (e.g. Mus[1, 2], Apodemus[3], Rattus[4]). The house mouse (Mus musculus) uses a system of lipocalin transporters of active volatile organic compounds– VOCs9–12, which together serve as signals In mice, these signals are manifested via expression of large quantities of male-biased[13] and highly homologous[14,15,16] major urinary proteins (MUPs) in the liver. It has been demonstrated that they are involved in the process of rapid ligand internalization by means of removing small organic molecules including odorants from nasal mucosa, this has been demonstrated for OBP5 (i.e. OBP1a in olfactory epithelia)[34] Data on these proteins from the mouse vaginal secretions were missing. We aimed to determine the level of correlation between the house mouse estrous cycle and the host regulation and degradation of bacteria to further the understanding of the emergence of complex odour mixtures

Objectives

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Conclusion