Which Animal's Pussy Looks Most Like a Woman's

Which Animal's Pussy Looks Most Like a Woman's

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• Published: 28 September 2015

A review of the human being vs. porcine female genital tract and associated immune system in the perspective of using minipigs as a model of human genital Chlamydia infection

Veterinary Research volume 46, Article number:116 (2015) Cite this article

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Abstract

Sexually transmitted diseases constitute major health issues and their prevention and handling go on to challenge the wellness care systems worldwide. Animal models are essential for a deeper understanding of the diseases and the development of safe and protective vaccines. Currently a proficient predictive non-rodent model is needed for the study of genital chlamydia in women. The hog has become an increasingly popular model for human diseases due to its close similarities to humans. The aim of this review is to compare the porcine and human being female genital tract and associated allowed organization in the perspective of genital Chlamydia infection. The comparing of women and sows has shown that despite some gross anatomical differences, the structures and proportion of layers undergoing cyclic alterations are very similar. Reproductive hormonal cycles are closely related, simply showing a slight difference in bicycle length and source of luteolysing hormone. The epithelium and functional layers of the endometrium show like cyclic changes. The allowed system in pigs is very similar to that of humans, even though pigs have a higher per centum of CD4⁺/CD8⁺ double positive T cells. The genital allowed system is also very 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 Göttingen Minipigs is non dominated by lactobacilli as in humans. The vaginal pH is around 7 in Göttingen Minipigs, compared to the more acidic vaginal pH around 3.5–5 in women. This review reveals important similarities between the human and porcine female reproductive tracts and proposes the sus scrofa every bit an advantageous supplementary model of human genital Chlamydia infection.

Tabular array of contents

one. Introduction

ii. Methods

3. The female person reproductive cycles

iv. The female person genital tract in pigs and humans

4.1 Gross anatomy

iv.2 Microscopic anatomy

4.2.i Vagina

4.2.2 Cervix

4.two.3 Uterus

4.2.4 Fallopian tubes

four.3 Anatomical and histological differences of relevance for a Chlamydia model

v. Genetics

half dozen. The porcine allowed system compared to the human immune system

half-dozen.1 The genital mucosal immune system

6.1.ane Distribution of immune cells in the genital tract tissue

vi.1.2 The humoral genital immune response

6.two Immunological differences of relevance for a Chlamydia model

seven. The vaginal flora and pH

8. Important differences betwixt rodents and minipigs

9. Conclusions

10. List of abbreviations

11. Competing interests

12. Authors' contributions

13. Authors' data

14. References

1. Introduction

Animal models are essential for gaining new insight into illness mechanisms of human genital diseases and the development of new condom strategies and treatments [1]. Predominantly rodents are used as models, within pre-clinical research, with mice often beingness the animal of choice [2,3]. Rodent models take clear advantages both regarding practical issues, by being pocket-sized and easy to handle, and economically affordable [2]. Furthermore, several genetically modified knockout strains are easily accessible, creating a unique opportunity to report the role of specific mediators in the immune response [four,five].

However, when evaluating animal models, dissimilar parameters are important to consider depending on the purpose of the model [vi]:

• Face validity; how well is the biology and symptoms of the human disease mimicked past the model.

• Predictive validity; how well is the effect of a drug/chemical compound or treatment mimicked by the model.

• Target validity; how similar a office the target of involvement 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 ever allow them to mimic the human form of infection and allowed response [four,5,vii,8]. The face validity and predictive validity is therefore prone to be insufficient, leaving a strong need for an intermediate and reliable model for the study of female person genital tract (FGT) infections and the development of appropriate vaccines against them [nine,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 demand for an intermediate pre-clinical/advanced non-rodent brute model.

The squealer has get 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 equally the Göttingen 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 bachelor 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 inquiry. Despite the physical size, there are no studies reporting whatsoever physiological differences between minipigs and conventional pigs. Furthermore, Göttingen Minipigs are partly derived from German Landrace pigs [xv].

It has recently been shown that pigs are susceptible to Chlamydia trachomatis, the agent causing human genital Chlamydia, and that pigs are suitable models for the study of Chlamydia pathogenesis and evaluation of vaccine candidates [xvi]. To evaluate the pig every bit a model of human being genital Chlamydia and to be able to interpret and extrapolate results critically and reliably, information technology is important to understand the morphological and functional similarities and differences betwixt 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 [17], Google Scholar [eighteen] and CAB ABSTRACTS database were searched, with the following keywords: Pig/swine/porcine, genital tract/reproductive tract/vagina/cervix/uterus/uterine body/uterine horn/Fallopian tubes, immunology/immune response/immunity, mucosal immunity/immune response, estrous bike/menstrual wheel/ sexual activity hormone regulation immunity, pig model/porcine model/animal model, sexually transmitted disease/genital infections, vaginal microbiota/flora/ecosystem.

Due to the very limited numbers of original published papers within the search criteria no twelvemonth limit was applied. The articles found were in the first line selected based on the abstract content, future the selected articles were evaluated in particular and based on relevance for this review and on the quality of the study, articles were included in this review. Studies on pregnancy immunology/embryology were not included.

iii. The female reproductive cycles

In women, the reproductive cycle (menstrual wheel) is described co-ordinate to the gonadal activity or endometrial changes [nineteen]. In pigs, the reproductive bike (estrous bike) is classified by the sexual behavior; estrus, where the pig is sexually receptive, or not-estrus [twenty]. Both of the cycles can be described with two phases; the luteal and the follicular stage, separated past ovulation (Figure1).

Effigy one

Comparison of the hormonal reproductive cycles in women and pigs. The estrous cycle in pigs begins and ends with ovulation/estrous [20,86]. The menstrual cycle in women begins and ends with the start of menstruum, with the ovulation in the middle of the bike [nineteen]. Otherwise, the length of the wheel and the hormonal fluctuations are very similar.

Full size image

In the grunter, a significant follicle growth occurs during the luteal phase (i.e. the follicular phase overlaps the luteal stage), resulting in a slightly shorter bicycle (xix–21 days) than in women, where the two phases are more stringent separated and the bike therefore lasts 28 days [19,20]. However, the hateful length is very similar between pigs and women.

The menses/flow, a bloody uterine belch, is specific for humans and some primates, usually lasts 3–7 days and is related to the kickoff of the follicular phase [19]. Both women and pigs are spontaneous ovulators and continuously cycling [21]. A comparing of the changes in the reproductive hormones during the reproductive cycles is shown in Figureane.

Both hormonal cycles are under control of the hypothalamic-pituitary-ovarian axis [nineteen,20]. If no pregnancy occurs during an estrous cycle in the pig, the non-pregnant uterus secretes prostaglandin F2α (PGF-2α), which makes the corpus luteum backslide (luteolysis) [20]. In women, the mechanism behind luteolysis is a scrap more than unclear, all the same, it is suggested that intraluteal PGF-2α plays a luteolysing role [22]. The of import differences between the porcine estrous and human being menstrual cycles are summarized in Tabular arrayane together with the same parameters in primates and mice, to show the level of similarity compared to these species.

Table 1 Comparison of reproductive-cycle parameters in women, non-human primates, minipigs and mice

Full size table

4. The female genital tract in pigs and humans

four.1. Gross anatomy

The porcine uterus differs from the human past being bicornuate [23] (Figure2). The bicornuate elongation of the uterine torso into two uterine horns creates a longer distance from the porcine cervix to the entrance of the Fallopian tubes than in women. In women the uterine trunk is approximately 7 cm long [24] while in a 1-year-old sexually mature Göttingen minipig gilded, each horn is an average 37.2 ± five.9 cm long (mean ± SD, n = 12, unpublished information).

Figure 2

Comparing of the gross beefcake and epithelium in the genital tract in women and pigs. The porcine uterus differs macroscopically from the human being simplex uterus by having bilateral horns (bicornuate) [23]. The porcine neck displays a feature characteristic, not found in women; the cervical pulvini (red arrow) [23]. Furthermore, the porcine urethra opens on the ventral surface of the vagina (majestic arrow) creating an urogenital sinus that opens to the outside through the common urogenital orifice [23]. In women, the urethra and vagina take its ain split up openings to the outside [19]. Otherwise the porcine vagina is like to the human one [92]. The human cervix is divided into the ectocervix that protrudes into the vaginal canal and the endocervix, creating the cervical lumen. An example of the local immune system in the female person genital tract is shown at the transition between the ecto- and endocervix.

Full size image

The cervix in Göttingen Minipigs is an average 7.five ± 0.85 cm long, whereas the homo cervix is around two–three cm [25]. The porcine cervix displays a characteristic feature, not found in women; the pulvini cervicales [23], which are a number of interdigitating prominent solid mucosal folds and protrusions throughout the length of the porcine cervix. Furthermore, the porcine urethra opens on the ventral surface of the vagina, creating a urogenital sinus that opens to the outside through the common urogenital orifice [eleven,xiv]. In women, the urethra and vagina have dissever openings [19].

The vagina in women is approximately 7 cm along the anterior curvature and nine cm forth the posterior curvature [25]. In Göttingen Minipigs the vagina is an average 13.8 ± 0.9 cm (mean ± SD, n = 12, unpublished data).

The Fallopian tubes are 7–14 cm long and 0.five–i.ii cm in external diameter in women [26] and an average 17.3 ± two.7 cm long and 0.4–0.5 cm in bore (mean ± SD, n = 12, unpublished data) in 1-year-former Göttingen Minipigs.

iv.2. Microscopic anatomy

Histology is a very important tool in the evaluation of pathological changes in creature models. Therefore, it is important to empathize morphological differences between pigs and humans [12]. Generally, and common for both pigs and humans, the wall of the FGT consists of 3 layers: the mucosal, the muscular and the outer serosal layers [21]. The tunica mucosa facing the lumen (the endometrium), is built by the inner lamina epithelialis, lamina propria (connective tissue) and the tela submucosa. The muscular layer (tunica muscularis) is built by stratum circulare and stratum longitudinale. The outer tunica serosa (the perimetrium), facing the peritoneal and pelvic cavities, is built by a lamina propria and lamina epithelialis [21]. In the peritoneal cavity the lamina epithelialis of the tunica serosa has a elementary squamous epithelium (visceral layer of the peritoneum) and in the pelvic cavity simply loose connective tissue (adventitia) [21].

4.ii.1. Vagina

The vagina is the entry site for most sexually transmitted diseases and therefore of great importance when comparison the pig model with humans [12]. The vaginal lamina epithelialis is made by non-keratinized stratified squamous epithelium and forms longitudinal folds called rugae in both women and pigs [12,27]. The porcine vaginal epithelium undergoes circadian alterations reaching a maximum thickness in the tardily proestrus [21]. The lamina propria consists of vascularized fairly dense connective tissue with no glands or mucosal muscular layer in both pigs and humans [21].

The vaginal mucosa is moisturized with secretions from the cervix. Cranially the porcine vagina is covered by a typical tunica serosa (i.e. loose connective tissue covered past the mesothelium) while caudally, a tunica adventitia, consisting of loose connective tissue is present. Both tunica serosa and adventitia incorporate big blood vessels, all-encompassing venous and lymphatic plexuses and numerous nervus bundles and ganglia [21,28]. In women, the vagina is externally covered by adventitia, primarily congenital with rubberband fibers attaching the vagina to the surrounding connective tissues and organs [27]. Tunica muscularis is as well similar for pigs and humans with an inner layer of circularly arranged polish muscle cells and an outer longitudinal layer, however the squealer can take a thin layer within the circular layer with longitudinally arranged fibers [21,27]. Studies have furthermore shown that the porcine vaginal permeability barrier, which is based on the lipid limerick and intercellular lipid lamellae in the epithelium, closely resembles that of humans [12].

4.ii.2. Cervix

The porcine neck has a thick, muscular wall rich in elastic fibers [21,23], whereas the human only contains small-scale amounts of smooth muscle and therefore mainly consists of dense connective tissue and elastic fibers [27].

The cervical lamina epithelialis differs between humans and pigs. In women the ectocervix has not-keratinized stratified squamous epithelium and the transformation zone separates it from the endocervix with a simple columnar epithelium [27]. In pigs, more than 90% of the cervix may have a vaginal type of epithelium with stratified squamous epithelium that undergoes circadian alterations. The porcine cervical epithelium changes between simple columnar, pseudostratified and stratified squamous epithelium, with primarily columnar in diestrus and primarily stratified in heat [21].

Common for both species is the simple columnar epithelium, which is mucinous with fungus secreting goblet cells. The amount of mucus secreted depends on the bike stage with an increased amount during estrus in pigs and midcycle in women (around ovulation). Much of the fungus passes to the vagina. Similarly the epithelium increase in thickness and edema develops during proestrus and estrus [21]. After ovulation the secretion decreases and the mucus becomes thicker [21].

4.2.3. Uterus

The homo myometrium (tunica muscularis) is congenital by three muscular layers. The thick middle layer (stratum vasculare) contains many large vessels [27]. This highly vascularized and well-innervated stratum vasculare is, however, indistinct in the pig [21]. A tela submucosa, with dense irregular connective tissue, is not present in the uterus in women, where the epithelium with lamina propria lie closely applied to the myometrium [27].

The epithelium is simple columnar in both women and pigs, but in the hog it increases significantly in height during heat and can plough into high pseudostratified columnar epithelium [21,29]. The endometrium and structure of the epithelial cells in women are also highly responsive to the hormonal changes and the thickness of the endometrium increases during the late proliferative phase [21,30].

The endometrium in pigs and women tin can exist characterized by two zones or layers; the superficial functional layer (stratum functionale) and the deeper basal layer (stratum basale). The functional layer undergoes cyclic changes and degenerates partly or completely subsequently pregnancy and oestrus in the pig [21]. In humans, the degenerated tissue is shed during menstruation [27]. In contrast to women, the pigs' basal layer is more cellular and gristly. It remains during all cyclic stages and is the source for restoration of the functional layer [21,27].

The uterine epithelium in pigs and women contains both ciliated cells and not-ciliated secretory cells [21] and branched and coiled (endometrial) glands that extend into the lamina propria [28]. In women, these glands are brusk and straight in the proliferative (follicular) phase and long and coiled in the secretory (luteal) stage [xxx]. In the porcine endometrium, growth and branching of the glands are stimulated by estrogen and the coiling and copious secretion by progesterone [21,29].

four.2.four. Fallopian tubes

The Fallopian tubes are of special interest in genital Chlamydia research, as they represent the site of infection, where sterilizing pathology develops in women [31]. The mucosa at the Fallopian tubes is folded into longitudinal folds (plicae) and the epithelium has non-ciliated secretory cells and ciliated cells that aid in moving the sperm upwards and the ovum downwards. The mucosal plicae in the ampulla accept secondary and sometimes third folds creating a circuitous organisation of epithelial-lined spaces. The epithelial lining is made of a single layer of columnar epithelial cells which sometimes is pseudostratified in pigs [21,32]. The epithelium undergoes cyclic changes with the greatest peak and ciliation in the late follicular phase, and atrophy together with loss of cilia in the luteal phase [30].

The Fallopian tube in both pigs and humans can be separated into three parts; the isthmus, which is communicating with the uterus, the ampulla (the heart thin walled function), and the infundibulum that has fimbriae to catch the oocyte, when it is released into the peritoneal cavity during ovulation. The human Fallopian tubes furthermore have an extra compartment called the intramural office. Fertilization will have place in the ampulla in both pigs (caudal ampulla) and humans [21,27].

4.3. Anatomical and histological differences of relevance for a Chlamydia model

The slight anatomical differences in the pig are of import to consider when choosing the inoculation road and when evaluating the ascending capacity of an infection. The porcine cervical pulvini make the admission from the vagina to the uterus complicated in pigs and should exist considered when choosing the inoculation method. Furthermore, the longer uterine body, in terms of uterine horns, is an important cistron for the face up validity of the hog model in evaluating ascending infections reaching the Fallopian tubes. In sexually immature conventional pigs inoculation with C. trachomatis SvE resulted in an ascending infection with bacterial replication in the Fallopian tubes [16].

A clear do good of the porcine anatomy is the human-like prominent Fallopian tubes in the hog that potentially allows studying the tubal pathology induced by a C. trachomatis infection.

Since the columnar epithelial cells are the target cells for the C. trachomatis [16,33] it is important to be enlightened of the slightly different localization of the target cells. In women the columnar epithelial cells are found together with the transitional cells found in the endocervix and upper FGT [34]. In the pig, the cervix is dominated by stratified squamous epithelium and columnar cells are just consistently found in the porcine uterus [21,35], and therefore not at the vagino-cervical transition as in women. It is therefore recommended to inoculate pigs directly into the uterus.

5. Genetics

The majority of genes expressed in porcine female person reproductive tissues are expressed in human FGT as well [36]. As further eluted to below, pigs share significantly more allowed-system related genes and proteins with humans than mice exercise [37].

6. The porcine immune organization compared to the human allowed organization

The porcine allowed organisation is well characterized and highly resembles that of humans [11,36], although there are some differences. One of the differences is the anatomy of the lymph nodes, which are inverted in pigs [38]. The inverted lymph node construction only affects the lymphocyte migration through the lymph node. Porcine lymphocytes mainly leave the lymph node through high endothelial venules instead of efferent lymph vessels, as they practise in humans [21,38,39]. Otherwise the physiology and immunologic reactions of the B and T cell areas in the lymph nodes do not differ [21,38].

Most of the protein mediators of the immune system are present with the same structure and function in humans and pigs and most of the immune cells identified in both species are similar [36,40]. The distribution of leukocytes in the blood is very similar in pigs and humans with a high percentage of neutrophils [41], however, within the lymphocyte populations, pigs have a higher proportion of CD4⁺CD8⁺ double positive T cells and ƴδ T cells in the claret. Otherwise the distribution of the different lymphocyte populations in pigs and humans is quite similar [eleven,36,40,42] as summarized in Table2.

Table two Lymphocyte subsets and antibodies in serum in humans and pigs

Total size table

The major histocompatibility complex (MHC) system in pigs, called the swine leukocyte antigen (SLA) system is very similar to the human leukocyte antigen system, in terms of polymorphic loci, haplotypes and differentiated expression on different cell populations [11,43]. However, resting porcine T lymphocytes can express MHCII before activation [11,43], whereas human T cells only express MHCII when activated [44].

All the cytokines in the human Th1/Th2/Th17/Treg paradigm have porcine orthologs [36], however, information technology is suggested that IL-4 might play a different role in pigs [45]. The expression and frequency of immunoglobulins are quite similar (Table2) except that IgD has not been demonstrated in pigs. Similar to humans, pigs have at least five IgG subclasses: IgG1, IgG2a, IgG2b, IgG3 and IgG4 [11]. Humans have two IgA heavy constant region genes (Cα) and therefore two subtypes of IgA designated IgA1 and IgA2 [46], whereas pigs only have one Cα cistron and therefore just i class of IgA [46-48]. Circulating IgA is mostly bone marrow derived and monomeric in humans [49], while circulatory IgA in pigs is half dimeric IgA and half monomeric IgA [50]. The dimeric proportion of circulating IgA in the grunter is, notwithstanding, primarily derived from the intestinal synthesis and lymph. Due to the hepatic pIgR-mediated transcytosis of polymeric IgA (pIgA) to the bile, the dimeric IgA is thought to be relatively short-lived in the circulation [50]. The hepatic polymeric immunoglobulin receptor (pIgR)-mediated transcytosis of pIgA happens in both humans and pigs [50].

In women, IgA2 is known to be the predominant isotype subclass in the genital secretions [51] while this distinction cannot be made in the porcine FGT secretions.

When modeling genital infections and evaluating vaccine responses, the toll-like receptors (TLR) play a crucial role in recognition of the pathogens and consecration of and controlling/directing the immune response. It has been shown that the porcine TLR organization is very similar to that of humans [41]. In terms of cytokines such as the neutrophil chemokine IL-8, the coding cistron carried by humans and pigs is an ortholog [41]. Furthermore, human- and porcine macrophages produce indoleamine two,3-dioxygenase (IDO) in response to lipopolysaccharide (LPS) and Interferon gamma (IFN-ɣ) stimulation [36,41].

half-dozen.1. The genital mucosal immune response

The genital mucosal allowed responses are of specific importance when using the pig as a model of human genital C. trachomatis infections. The genital allowed response is challenged in the sense that information technology has to tolerate sperm, the semi-allogeneic conceptus and the commensal vaginal flora, while it must mount defense responses against sexually transmitted pathogens in society to eliminate them [52].

The genital allowed system consists of both innate and adaptive factors. The innate system is primarily built past the epithelial barrier, the production of antimicrobial agents and cytokines by the epithelial cells and the innate immune cells [twoscore,53]. Both innate and adaptive humoral mediators and immune cells in the genital allowed system are regulated past progesterone and estradiol and therefore fluctuate through the menstrual or estrous cycles [53].

The epithelial cells in the FGT with interconnecting tight junctions play an important function in the immune protection past providing a stiff physical barrier, transporting antibodies to the mucosal surface, secreting antibacterial compounds and by recruiting immune cells [54,55]. The sex activity hormones regulate the structural changes in the epithelium during the wheel. Nether the influence of estrogen, the integrity and strength of tight junctions in the epithelial barrier, is significantly weakened in women [54,56]. The secretion of antimicrobial compounds is also suppressed during the midcycle in women [53,57].

To preserve an intact protective barrier, the genital mucosal immune response is ofttimes not-inflammatory to avoid inflammation-mediated injuries unremarkably caused by phagocytic action and complement activation [55]. Near of the antigens in the FGT are therefore met with mucosal tolerance [55].

half dozen.one.ane. Distribution of allowed cells in the genital tract tissue

The genital mucosa does not have immune anterior sites such equally the nasal-associated lymphoid tissue or abdominal Peyer's patches [55]. Thus, the genital mucosa lacks an organized center to disseminate antigen-stimulated B and T lymphocytes to the distinct sites of the mucosa. However, lymphoid aggregates (LA) are present in the female genital mucosa of both pigs [35] and humans [55] and leukocytes are dispersed throughout the mucosa of the FGT [58] every bit illustrated in Effigyii.

The LA are located in the basal layer of the endometrium close to the base of operations of the uterine epithelial glands and congenital by a core of B cells surrounded by T cells and an outer layer of macrophages [58]. The T cells in the LA are primarily CD8⁺ T cells, however, CD4⁺ T cells are besides present in variable numbers in the LA [58]. Both CD4⁺ and CD8⁺ T cells are found every bit intraepithelial lymphocytes and dispersed throughout the subepithelial tissue [58]. Aggregates of NK cells can also exist establish in the endometrium only they are placed in close contact with the luminal epithelium [58].

The leukocytes present in the FGT covers macrophages, dendritic cells, NK cells, neutrophils, B cells and T cells [53,59,60] with lymphocytes being the predominant immune jail cell type in both pigs and women [35,61,62]. The number of immune cells and the size of LA are under strong hormonal influence and fluctuate through the cycle [55,58] as summarized in Table3.

Table three Fluctuations in allowed cells and antibody levels in the female person genital tract during the hormonal cycles. Both women and pigs show regional differences in the hormonal regulation of the genital immune organization. The antibody fluctuations seem like in women and pigs but the influx of neutrophils during estrus is specific for pigs. It should be noted that the porcine studies are rather onetime and only including few animals. LGT – Lower genital tract, UGT – upper genital tract

Full size tabular array

6.one.2. The humoral genital allowed response

The immunoglobulins plant in the FGT either take been locally produced by subepithelial plasma cells, or derived from the circulation [63]. Although IgG producing plasma cells can be institute in the FGT [64], genital IgG is mainly derived from the circulation [63,65-67] and transported to the mucosal surface by mechanisms such every bit passive leakage, paracellular diffusion or receptor-mediated transport [63,65]. In contrast, genital IgM and IgA are primarily derived from the subepithelial plasma cells [65,68-seventy] with upward to 95% of the porcine IgA beingness locally produced [71] and up to 70% of the IgA being locally produced in women [55]. When produced locally, the polymeric secretory IgA (sIgA) is actively transported across the mucosal epithelia cells by the polymeric immunoglobulin receptor (pIgR) [65,66]. The secretion of sIgA primarily takes place in the cervix due to the focused pIgR localization in the cervix in women [72]. The pIgR is also expressed in the uterus, but to a lesser extent and in variable levels due to hormonal regulation [55].

Normally, sIgA is the predominant isotype plant in mucosal secretions, such every bit the abdominal fluid. However, in the secretions from the FGT, at that place is a greater proportion of IgG compared to sIgA [65,73-75].

The FGT humoral immune response is under strong hormonal influence during the menstrual or estrous cycle [57,74]. The circadian fluctuations in the antibody levels are compared in Tableiii. The information on cycle-dependent variations in the level of antibodies in pigs is sparse and more than knowledge is needed within this surface area.

half dozen.1.3. Immunological differences of relevance for a Chlamydia model

The nigh important immunological deviation with potential influence on Chlamydia models is the slightly different influx of immune cells in the porcine FGT, characterized by an increase in neutrophils during oestrus. It should be kept in listen that this increased innate response during heat could influence the institution of infection.

7. The vaginal flora and pH

In women, the vaginal microflora is known to play an important role in the innate genital immune system by inhibiting the colonization of pathogens [76,77]. Lactobacilli and other lactic acrid producing leaner are particularly associated with equilibrium in the vaginal flora and inhibition of the growth of pathogens [76,78,79].

16S rRNA cistron sequencing has immune a thorough identification of the vaginal flora in women and the nearly mutual leaner are: Lactobacillus spp., Staphylococcus spp., Ureaplasma urealyticum, Corynebacterium vaginale, Streptococcus spp., Peptostreptococcus spp., Gardnerella vaginalis, Bacteroides spp., Mycoplasma spp., Enterococcus spp., Escherichia coli, Veillonella spp., Bifidobacterium spp. and Candida spp.. However, the species composition can be very different between individuals and during the menstrual cycle [52,76,79]. In women, the lactic acid producing bacteria play an important part by contributing to an acidic surroundings with a pH of 3.5–v [52].

In good for you pigs the vaginal flora has been characterized past civilisation dependent methods and was found to include both aerobic and anaerobic bacteria with the about prominent being the following: Streptococcus spp., E. coli, Staphylococcus spp., Corynebacterium spp., Micrococcus spp. and Actinobacillus spp. [80]. Based on our genetic screening of vaginal swabs from Göttingen Minipigs, information technology is evident that the above mentioned leaner are present, just not dominating. Streptococcus spp. constituted on average i.iv% on the vaginal flora, East. coli iii.7%, and Staphylococcus 0.4%. Furthermore, we constitute that the vaginal flora was not dominated by lactobacillus as in humans. Lactobacillaceae constituted on average 3.9% of the total vaginal flora in Göttingen Minipigs. The vaginal flora in Göttingen Minipigs seemed to be dominated past the following: unclassified genera belonging to Gammaproteobacteria, unclassified genera from Clostridiales, Yersinia, Paenibacillus, Listeria, Syntrophus, Heliobacterium, Faecalibacterium, Kineococcus and Proteus (unpublished information).

An old study showed that the FGT mean pH in estrus in pigs is 7.02 in the oviduct, 6.98 in the uterus, 7.49 in the neck and vi.61 in the vagina [81]. Our ain data, based on vaginal pH measurements with a pH electrode (Mettler-Toledo InLab® Surface Electrode, Sigma-Aldrich Broendby, Denmark), confirmed that the vaginal pH is just effectually neutral (~7) in both prepubertal and sexually mature Göttingen Minipigs.

viii. Important differences between rodents and minipigs

The chief aim of this review was to compare the female reproductive physiology of humans and pigs, withal, as a concluding section, we found it important to highlight where the minipig shows significant differences to the normally used murine model in Chlamydia research. Similar comparisons of humans and mice has been done elsewhere [4,82,83], and only main points will exist included hither.

The reproductive cycle is significantly shorter in mice, having a iv–5 twenty-four hour period bike due to the lack of progesterone-producing corpora lutea and thereby a luteal phase, if no coital stimulation occurs [84]. Anatomically, the murine uterus is bicornuate and much smaller than the porcine and human ones [83]. Histologically, the vagina displays keratinized squamous epithelium during rut, whereas porcine and human being epithelium does not keratinize [83].

Inside the immune arrangement, the composition of circulating leukocytes is significantly different with a lower per centum of neutrophils and a corresponding higher affluence of lymphocytes in mice compared to pigs and humans [82]. Furthermore, and importantly for the Chlamydia model, murine macrophages exercise not produce IDO in response to LPS and IFN-ɣ stimulation, by dissimilarity humans and porcines do [36,41]. Furthermore, murine macrophages produce nitric oxide (NO) in response to stimulation with LPS, whereas human and porcine macrophages do not [36]. There is also a great difference in the expression of cytokines such as IL-eight, a potent neutrophil chemokine expressed in pigs and humans, but not in mice. In mice keratinocyte-derived chemokine and macrophage inflammatory protein-2 are considered to be the IL-viii counterpart [41].

In the FGT, the influx of immune cells happens slightly differently in mice, compared to pigs and humans. In the murine endometrium an influx of leukocytes is seen in the proestrus, during heat the leukocytes are almost absent, during metestrus they are prominent and during diestrus an infiltration is seen [83]. The fluctuations in antibody levels in the murine FGT shows a like pattern for IgG, with a lower level during estrus, while for IgA, it is opposite that of pigs and women, with mice having a higher level during rut [85].

ix. Conclusions

This comparison of the porcine and human being FGT reveals articulate similarities and gives an understanding of the differences between the species. Despite the bicornuate porcine uterus with a urogenital sinus and cervical pulvini, the anatomical and morphological construction and proportion of layers with cyclic alterations is very similar in humans and pigs. The hormonal cycles are closely related, just differing slightly in bike elapsing, and origin of luteolysing hormone. The general immune system and the immune system associated with the FGT show cracking similarities. The antibiotic levels on the genital mucosa shows similar cyclic fluctuations in pigs and women, but the immune jail cell infiltration in the genital mucosa differs slightly between women and pigs, namely in the influx of neutrophils in the porcine endometrium during estrus. The porcine vaginal flora differs from the human by not beingness dominated by lactobacilli and the vaginal pH is slightly higher in pigs than in women.

Information technology is difficult to tell the exact significance of the differences and similarities between the FGT in women and pigs and interpretation of information from brute models should always be done with caution. The similarities establish in this review, however, advise that the pig adds a greater predictive value to FGT studies than what can be achieved by studies in rodent models. Not-human primates is the species most closely related to humans, but upstanding concerns and the relative ease of working with pigs suggest the hog to be an advantageous model of human reproductive disorders such equally C. trachomatis infection.

Abbreviations

APC:

Antigen presenting cell

FGT:

Female genital tract

IDO:

Indoleamine 2,3-dioxygenase

IFN-ɣ:

Interferon gamma

Ig:

Immunoglobulin

LA:

Lymphoid aggregates

LGT:

Lower genital tract

LPS:

Lipopolysaccharide

MHC:

Major Histocompatibility complex

NHP:

Non-human primates

NO:

Nitric Oxide

PGF-2α:

Prostaglandin-F2α

pIgR:

Polymeric immunoglobulin receptor

pIgA:

Polymeric immunoglobulin A

sIgA:

Secretory Immunoglobulin A

SLA:

Swine leukocyte antigen

TLR:

Toll-similar receptor

UGT:

Upper genital tract

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Affiliations

1. Section for Veterinary Reproduction and Obstetrics, Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

   Emma Lorenzen & Jørgen S. Agerholm

2. Chlamydia Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark

   Emma Lorenzen & Frank Follmann

3. Section for Immunology and Vaccinology, National Veterinarian Plant, Technical University of Denmark, Copenhagen, Denmark

   Gregers Jungersen

Corresponding writer

Correspondence to Emma Lorenzen.

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11. Competing interests

The authors declare that they have no competing interests.

12. Authors' contributions

EL performed the literature study, drafted the structural blueprint of the review and was responsible for writing the manuscript. FF, GJ and JSA contributed intellectually with a critical revision of the manuscript. All authors have read and approved the final manuscript.

13. Authors' information

EL is DVM and currently a PhD pupil at University of Copenhagen and Statens Serum Institut, Kingdom of denmark. For 2 years, EL has been working on a project, focusing on the development of a minipig model for human genital Chlamydia, for evaluation of vaccine candidates. FF is the Head of Chlamydia Vaccine Research at Statens Serum Institut, Denmark. FF is responsible for pre-clinical antigen discovery, vaccine design and formulation. GJ is professor in Immunology and Vaccinology at the National Veterinary Found with special expertise in porcine and bovine immune responses and immunological correlates of vaccine mediated protection. JSA is professor in Veterinary Reproduction and Obstetrics with a PhD in pathology. JSA has studied genital tract inflammation for several years and has supervised the development of a porcine model for genital Chlamydia in women since 2010.

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Lorenzen, E., Follmann, F., Jungersen, Thou. et al. A review of the human vs. porcine female genital tract and associated allowed organisation in the perspective of using minipigs as a model of human genital Chlamydia infection. Vet Res 46, 116 (2015). https://doi.org/10.1186/s13567-015-0241-ix

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• Received: 07 May 2015

• Accepted: 11 August 2015

• Published: 28 September 2015

• DOI : https://doi.org/10.1186/s13567-015-0241-nine

Keywords

• Fallopian Tube
• Female Genital Tract
• Lymphoid Aggregate
• Vaginal Flora
• Swine Leukocyte Antigen

Which Animal's Pussy Looks Most Like a Woman's

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