Studies on pregnancy immunology/embryology were not included. 3. similar in terms of the cyclic fluctuations in the mucosal antibody levels, but differs slightly regarding immune cell infiltration in the genital mucosa – predominantly due to the influx of neutrophils in the porcine endometrium during estrus. The vaginal flora in G?ttingen Minipigs is not dominated by lactobacilli as in humans. The vaginal pH is around 7 in G?ttingen Minipigs, compared to the more acidic vaginal pH around 3.5C5 in women. This review reveals important similarities between the human and porcine female reproductive tracts and proposes the pig as an advantageous supplementary model of human genital contamination. Table of contents 1. Introduction 2. Methods 3. The female reproductive cycles 4. The female genital tract in pigs and humans 4.1 Gross anatomy 4.2 Microscopic anatomy 4.2.1 Vagina 4.2.2 Cervix 4.2.3 Uterus 4.2.4 Fallopian tubes 4.3 Anatomical and histological differences of relevance for a model 5. Genetics 6. The porcine immune system compared to the human immune system 6.1 The genital mucosal immune system 6.1.1 Distribution of immune cells in the genital tract tissue 6.1.2 The humoral genital immune response 6.2 Immunological differences of relevance for any model 7. The vaginal flora and pH 8. Important differences between rodents and minipigs 9. Conclusions 10. List of abbreviations 11. Competing interests 12. Authors contributions 13. Authors information 14. Recommendations 1. Introduction Animal models are essential for gaining new insight into disease mechanisms of human genital diseases and the development of new prophylactic strategies and treatments [1]. Predominantly rodents are used as models, within pre-clinical research, with mice often being the animal of choice [2,3]. Rodent models have SNS-032 (BMS-387032) obvious advantages both regarding practical issues, by being small and easy to handle, and economically affordable [2]. Furthermore, SNS-032 (BMS-387032) several genetically altered knockout strains are easily accessible, creating a unique opportunity to Rabbit Polyclonal to SEMA4A study the role of specific mediators in the immune response [4,5]. However, when evaluating animal models, different parameters are important to consider depending on the purpose of the model [6]: Face validity; how well is the biology and symptoms of the human disease mimicked by the model. Predictive validity; how well is the effect of a drug/compound or treatment mimicked by the model. Target validity; how comparable a role the target of SNS-032 (BMS-387032) interest plays in the model compared to humans. Despite the many advantages of rodent models, rodents show a number of differences to humans in terms of size, anatomy, physiology and immunology that do not usually allow them to mimic the human course of contamination and immune response [4,5,7,8]. The face validity and predictive validity is usually therefore prone to be insufficient, leaving a strong need for an intermediate and reliable model for the study of female genital tract (FGT) infections and the development of appropriate vaccines against them [9,10]. Non-human primates (NHP) are the animals most closely related to humans and therefore likely to show the greatest face- and predictive validity. However, due to ethical concerns and costly experiments associated with studies in NHP, there is a need for an intermediate pre-clinical/advanced non-rodent animal model. The pig has become an increasingly popular model, especially within the fields of atherosclerosis and diabetes research, because of its physiological and anatomical similarities to humans [11-13]. Pigs of reduced body size such as the G?ttingen Minipigs offer a great advantage by having a smaller size at sexual maturity and a lower growth rate than conventional pigs [14]. Furthermore, such breeds are available as specific pathogen free from specialized breeding companies [15]. Wherever possible, this review will focus on the minipig, since this has been the experimental animal of choice in our research. Despite the SNS-032 (BMS-387032) physical size, there are no studies reporting any physiological differences between minipigs and conventional pigs. Furthermore, G?ttingen Minipigs are partly derived from German Landrace pigs [15]. It has recently been shown that pigs are susceptible to the agent causing human genital pathogenesis and evaluation of vaccine candidates [16]. To evaluate the pig as a model of human genital and to be able to interpret and extrapolate results critically and reliably, it is important to understand the morphological and functional similarities SNS-032 (BMS-387032) and differences between the human and porcine female reproductive systems. The purpose of this review is to provide the basis for this understanding. 2. Methods The PubMed database.