The dimeric proportion of circulating IgA in the pig is, however, 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.
It has been shown that the porcine TLR system is very similar to that of humans [ 41 ]. In terms of cytokines such as the neutrophil chemokine IL-8, the coding gene carried by humans and pigs is an ortholog [ 41 ].
The genital mucosal immune responses are of specific importance when using the pig as a model of human genital C. The genital immune response is challenged in the sense that it has to tolerate sperm, the semi-allogeneic conceptus and the commensal vaginal flora, while it must mount defense responses against sexually transmitted pathogens in order to eliminate them [ 52 ].
The genital immune system consists of both innate and adaptive factors. The innate system is primarily built by the epithelial barrier, the production of antimicrobial agents and cytokines by the epithelial cells and the innate immune cells [ 40 , 53 ].
Both innate and adaptive humoral mediators and immune cells in the genital immune system are regulated by 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 role in the immune protection by providing a strong physical barrier, transporting antibodies to the mucosal surface, secreting antibacterial compounds and by recruiting immune cells [ 54 , 55 ].
The sex hormones regulate the structural changes in the epithelium during the cycle. Under 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 often non-inflammatory to avoid inflammation-mediated injuries usually caused by phagocytic activity and complement activation [ 55 ].
Most of the antigens in the FGT are therefore met with mucosal tolerance [ 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 ] as illustrated in Figure 2. The LA are located in the basal layer of the endometrium close to the base of the uterine epithelial glands and built by a core of B cells surrounded by T cells and an outer layer of macrophages [ 58 ].
Aggregates of NK cells can also be found in the endometrium but 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 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 Table 3. Fluctuations in immune cells and antibody levels in the female genital tract during the hormonal cycles. Both women and pigs show regional differences in the hormonal regulation of the genital immune system. The antibody fluctuations seem similar 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 old and only including few animals. The immunoglobulins found in the FGT either have been locally produced by subepithelial plasma cells, or derived from the circulation [ 63 ].
Although IgG producing plasma cells can be found in the FGT [ 64 ], genital IgG is mainly derived from the circulation [ 63 , 65 - 67 ] and transported to the mucosal surface by mechanisms such as passive leakage, paracellular diffusion or receptor-mediated transport [ 63 , 65 ]. 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 ]. Usually, sIgA is the predominant isotype found in mucosal secretions, such as the intestinal fluid. The FGT humoral immune response is under strong hormonal influence during the menstrual or estrous cycle [ 57 , 74 ]. The cyclic fluctuations in the antibody levels are compared in Table 3.
The information on cycle-dependent variations in the level of antibodies in pigs is sparse and more knowledge is needed within this area.
The most important immunological difference 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 estrus. It should be kept in mind that this increased innate response during estrus could influence the establishment of infection.
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 acid producing bacteria are particularly associated with equilibrium in the vaginal flora and inhibition of the growth of pathogens [ 76 , 78 , 79 ]. 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 role by contributing to an acidic environment with a pH of 3. In healthy pigs the vaginal flora has been characterized by culture dependent methods and was found to include both aerobic and anaerobic bacteria with the most prominent being the following: Streptococcus spp. Streptococcus spp.
Furthermore, we found that the vaginal flora was not dominated by lactobacillus as in humans. Lactobacillaceae constituted on average 3. An old study showed that the FGT mean pH in estrus in pigs is 7.
The primary aim of this review was to compare the female reproductive physiology of humans and pigs, however, as a concluding section, we found it important to highlight where the minipig shows significant differences to the commonly used murine model in Chlamydia research. Similar comparisons of humans and mice has been done elsewhere [ 4 , 82 , 83 ], and only main points will be included here.
The reproductive cycle is significantly shorter in mice, having a 4—5 day cycle 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 estrus, whereas porcine and human epithelium does not keratinize [ 83 ]. Within the immune system, the composition of circulating leukocytes is significantly different with a lower percentage of neutrophils and a corresponding higher abundance of lymphocytes in mice compared to pigs and humans [ 82 ].
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-8, a strong 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-8 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 estrus 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 similar 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 estrus [ 85 ].
This comparison of the porcine and human FGT reveals clear 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, only differing slightly in cycle duration, and origin of luteolysing hormone. The general immune system and the immune system associated with the FGT show great similarities. The antibody levels on the genital mucosa shows similar cyclic fluctuations in pigs and women, but the immune 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 being dominated by lactobacilli and the vaginal pH is slightly higher in pigs than in women. It is difficult to tell the exact significance of the differences and similarities between the FGT in women and pigs and interpretation of data from animal models should always be done with caution. The similarities found in this review, however, suggest that the pig adds a greater predictive value to FGT studies than what can be achieved by studies in rodent models.
Non-human primates is the species most closely related to humans, but ethical concerns and the relative ease of working with pigs propose the pig to be an advantageous model of human reproductive disorders such as C. Competing interests. EL performed the literature study, drafted the structural design of the review and was responsible for writing the manuscript. All authors have read and approved the final manuscript.
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 responsible for pre-clinical antigen discovery, vaccine design and formulation.
GJ is professor in Immunology and Vaccinology at the National Veterinary Institute with special expertise in porcine and bovine immune responses and immunological correlates of vaccine mediated protection. JSA has studied genital tract inflammation for several years and has supervised the development of a porcine model for genital Chlamydia in women since Emma Lorenzen, Email: kd.
Frank Follmann, Email: kd. Gregers Jungersen, Email: kd. Agerholm, Email: kd. National Center for Biotechnology Information , U. Journal List Vet Res v. Vet Res. Published online Sep Author information Article notes Copyright and License information Disclaimer. Corresponding author. Received May 7; Accepted Aug This article has been cited by other articles in PMC. Abstract Sexually transmitted diseases constitute major health issues and their prevention and treatment continue to challenge the health care systems worldwide.
Table of contents 1. Introduction 2. Methods 3. The female reproductive cycles 4. The female genital tract in pigs and humans 4. Genetics 6. The porcine immune system compared to the human immune system 6. The vaginal flora and pH 8. Important differences between rodents and minipigs 9. Conclusions List of abbreviations Competing interests 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 ].
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. The female reproductive cycles In women, the reproductive cycle menstrual cycle is described according to the gonadal activity or endometrial changes [ 19 ].
Open in a separate window. Figure 1. Table 1 Comparison of reproductive-cycle parameters in women, non-human primates, minipigs and mice.
Women menstrual [ 25 , 87 ] Non-humane primates menstrual [ 88 , 89 ] Minipigs estrous [ 11 , 20 , 90 ] Mice estrous [ 84 , 91 ] Cyclicity Continuous cycling Baboons : continuous cycling in captivity Rhesus Macaque : seasonal poly-oestral. Numbers are keyed to body parts and internal organs as follows: 1. Vulva: The opening of the birth canal. Vagina: The area from just inside the vulva to the cervix.
Textbook of Veterinary Anatomy, Ed St. University of Zaragoza Falceto, M. Hafez ESA. Reproduction in farm animals. Veterinary Endocrinology and Reproduction. Share this news! Facebook Twitter LinkedIn Email. Related Posts. Tips for seasonal infertility Tips for seasonal infertility. Magapor will hold the Forum for Swine Reproduction Specialists. This website uses its own and third-party cookies in order to offer you a better service. Accept them and continue browsing to enjoy all the content.
I accept Cookies settings. Cookies policy. Cerrar Privacy Overview This website uses cookies to improve your experience while you navigate through the website. Out of these cookies, the cookies that are categorized as necessary are stored on your browser as they are as essential for the working of basic functionalities of the website.
We also use third-party cookies that help us analyze and understand how you use this website. These cookies will be stored in your browser only with your consent. You also have the option to opt-out of these cookies.
But opting out of some of these cookies may have an effect on your browsing experience. Necessary Necessary. Necessary cookies are absolutely essential for the website to function properly. The blastocysts can migrate from one horn to another during this stage. One of the most critical periods of pregnancy is from approximately day after mating.
The blastocysts, elongate into long feet , stringy masses, and they begin to attach to the uterine wall. The greatest potential loss in litter size may occur during this stage of development because of attachment failures.
On the average, 17 ova are shed at estrus yet only about 12 are accounted for as blastocysts when attachment complete. There is thought to be some factor s which limit the number of blastocysts that can attach in a given uterus. Research has shown that overcrowding is not a major limiting factor. Embryonic survival may be related to certain uterine secretions which have not presently been well defined.
Environmental stressors such as high temperatures and fighting as a result of mixing or regrouping animals also adversely influence implantation and embryo survival. Generally, the presence of at least four blastocysts are required in order for pregnancy to continue.
Each embryo is surrounded by a separate series of fluid-filled membranes , the amnion and chorion, which are comprise the placenta. These membranes help to protect and nourish the growing embryo. Nutrients, waste, gases and certain antibodies cross the membranes between the dam and embryos blood systems. It is the presence or absence of this fluid that is detected by the commonly used "ultrasound" pregnancy diagnosis equipment. The fetal period begins at approximately day Sexes may be easily determined by external examination and the main systems of the body are more well defined.
The fetus can now be called a miniature adult. Fetal orientation is random; some are head to head, some are tail to tail and some are head to tail. At farrowing, about half are born tail first and half are born head first.
Embryos which die before day are usually reabsorbed by the dam. However, progressive calcification of the skeleton begins to occur from day 36 onward and deaths occurring after this point will result in mummification. Hair shafts begin to emerge but remain trapped under a skin layer until close to birth. Throughout gestation, the uterus gradually enlarges from about 2 to 3 pounds at mating to up to 60 pounds, including fetal contents, during the last week.
The average gestation length or time from conception until farrowing is days.
0コメント