Expression and Clinical Significance of Non B Cell-Derived Immunoglobulins in the Urinary System and Male Reproductive System.

The urinary system comprises kidneys, ureters, bladder, and urethra with its primary function being excretion, referring to the physiological process of transporting substances that are harmful or surplus out of the body. The male reproductive system consists of gonads (testis), vas deferens, and accessory glands such as the prostate. According to classical immunology theory, the tissues and organs mentioned above are not thought to produce immunoglobulins (Igs), and any Ig present in the relevant tissues under physiological and pathological conditions is believed to be derived from B cells. For instance, most renal diseases are associated with uncontrolled inflammation caused by pathogenic Ig deposited in the kidney. Generally, these pathological Igs are presumed to be produced by B cells. Recent studies have demonstrated that renal parenchymal cells can produce and secrete Igs, including IgA and IgG. Glomerular mesangial cells can express and secrete IgA, which is associated with cell survival and adhesion. Likewise, human podocytes demonstrate the ability to produce and secrete IgG, which is related to cell survival and adhesion. Furthermore, renal tubular epithelial cells also express IgG, potentially involved in the epithelial-mesenchymal transition (EMT). More significantly, renal cell carcinoma, bladder cancer, and prostate cancer have been revealed to express high levels of IgG, which promotes tumour progression. Given the widespread Ig expression in the urinary and male reproductive systems, continued efforts to elucidate the roles of Igs in renal physiological and pathological processes are necessary.

Effects of female bone marrow transplantation on male reproductive organs.

Graft-versus-host disease (GVHD), an adverse effect after bone marrow transplantation (BMT), may affect male reproductive function. It is hypothesized that a sex-mismatched BMT induces GVHD in male reproductive organs because female immune cells are not immunologically tolerant to specific antigens of the male organs. However, this hypothesis has not been experimentally verified using male (M) recipient animals following BMT from the female (F) donors. Therefore, the aim of the present study is to examine whether the female BMT to males (F→M group) induces some GVHD reactions in the testis and the other male reproductive organs. The results showed that no inflammation was found in recipients of the male BMT to males (M→M group), whereas significant inflammatory cell responses lasting for at least 4 months were induced in testis, epididymis, prostate and preputial gland in some mice of F→M group. The most severe lesion was found in the preputial gland, in which lymphocytic inflammation was accompanied by loss of glandular acini, thickening of the interstitum and increased cytokines such as TNF-α and IFN-γ. Western blot analyses revealed that sera from the F→M group reacted with various antigens of the male reproductive organs. These results indicate that transplanted female immune cells may recognize the male reproductive organs as immunologically foreign ones and induce chronic GVHD, which may affect male reproductive function.

Tissue-resident immunity in the female and male reproductive tract.

The conception of how the immune system is organized has been significantly challenged over the last years. It became evident that not all lymphocytes are mobile and recirculate through secondary lymphoid organs. Instead, subsets of immune cells continuously reside in tissues until being reactivated, e.g., by a recurring pathogen or other stimuli. Consequently, the concept of tissue-resident immunity has emerged, and substantial evidence is now available to support its pivotal function in maintaining tissue homeostasis, sensing challenges and providing antimicrobial protection. Surprisingly, insights on tissue-resident immunity in the barrier tissues of the female reproductive tract are sparse and only slowly emerging. The need for protection from vaginal and amniotic infections, the uniqueness of periodic tissue shedding and renewal of the endometrial barrier tissue, and the demand for a tailored decidual immune adaptation during pregnancy highlight that tissue-resident immunity may play a crucial role in distinct compartments of the female reproductive tract. This review accentuates the characteristics of tissue-resident immune cells in the vagina, endometrium, and the decidua during pregnancy and discusses their functional role in modulating the risk for infertility, pregnancy complications, infections, or cancer. We here also review data published to date on tissue-resident immunity in the male reproductive organs, which is still a largely uncharted territory.

Natural killer and NKT cells in the male reproductive tract.

Natural killer (NK) cells are important effector lymphocytes that play a pivotal role in the innate and adaptive immune responses to tumors and viral infection. NKT cells are a heterogeneous group of T cells that share properties with both T cells and NK cells. They display immunoregulatory properties as they facilitate the cell-mediated immune response to tumors and infectious diseases, and inhibit cell-mediated immunity associated with autoimmune diseases and allograft rejection. However, the roles of NK and NKT cells in the male reproductive tract remain largely unexplored, in particular, NKT cells, tissue distribution, and state of health or disease. Infection and inflammation of the male genital tract are thought to be the primary etiological factors of male infertility. In this review, we considered this complex and rapidly growing field. We summarize the recent findings and the characterization and roles of NK and NKT cells in the male reproductive tract, including the testis, epididymis, prostate, seminal vesicle, and semen, to enhance our understanding of the immunological mechanisms of male infertility and for the design effective vaccines for male reproductive health in the future.

Inflammation and HIV Transmission in Sub-Saharan Africa.

While the per-contact risk of sexual HIV transmission is relatively low, it is fourfold higher in sub-Saharan Africa, and this may partly explain the major global disparities that exist in HIV prevalence. Genital immune parameters are key determinants of HIV transmission risk, including epithelial integrity and the presence of highly HIV-susceptible intraepithelial or submucosal CD4+ T cell target cells. Biological parameters that may enhance mucosal HIV susceptibility in highly HIV-affected regions of sub-Saharan Africa include increased levels of mucosal inflammation, which can affect both epithelial integrity and target cell availability, as well as the increased mucosal surface area that is afforded by an intact foreskin, contraceptive choices, and intravaginal practices. There are multifactorial causes for increased mucosal inflammation, with the prevalence and nature of common co-infections being particularly relevant.

Chlamydia trachomatis infection of the male genital tract: an update.

Chlamydia trachomatis (CT) is the most prevalent cause of sexually transmitted diseases. Although the prevalence of chlamydial infection is similar in men and women, current research and screening are still focused on women, who develop the most severe complications, leaving the study of male genital tract (MGT) infection underrated. Herein, we reviewed the literature on genital CT infection with special focus on the MGT. Data indicate that CT certainly infects different parts of the MGT such as the urethra, seminal vesicles, prostate, epididymis and testis. However, whether or not CT infection has detrimental effects on male fertility is still controversial. The most important features of CT infection are its chronic nature and the presence of a mild inflammation that remains subclinical in most individuals. Chlamydia antigens and pathogen recognition receptors (PRR), expressed on epithelial cells and immune cells from the MGT, have been studied in the last years. Toll-like receptor (TLR) expression has been observed in the testis, epididymis, prostate and vas deferens. It has been demonstrated that recognition of chlamydial antigens is associated with TLR2, TLR4, and possibly, other PRRs. CT recognition by PRRs induces a local production of cytokines/chemokines, which, in turn, provoke chronic inflammation that might evolve in the onset of an autoimmune process in genetically susceptible individuals. Understanding local immune response along the MGT, as well as the crosstalk between resident leukocytes, epithelial, and stromal cells, would be crucial in inducing a protective immunity, thus adding to the design of new therapeutic approaches to a Chlamydia vaccine.

Rough virulent strain of Brucella ovis induces pro- and anti-inflammatory cytokines in reproductive tissues in experimentally infected rams.

The ovine brucellosis caused by Brucella ovis has tropism for reproductive tissues but until now the mechanism of bacterial persistence is not understood. Cytokine expression profiles were studied for 8 months in rams after being experimentally infected with the rough virulent strain of B. ovis (R-B. ovis) to study the pathogenesis of B. ovis and immune mechanism possibly associated to bacteria tropism and persistence. The messenger RNA (mRNA) expression levels of interleukin-1α (IL-1α), IL-1ß, IL-6, IL-10, IL-12, interferon-γ (INF-γ) and tumour necrosis factor-α (TNF-α) cytokines were quantified by real-time quantitative RT-PCR (qRT-PCR) in reproductive tissues (epididymus, testicles, ampolae, vesicular glands and bulbourethral glands), and non-reproductive (liver, spleen and kidneys) tissues at 30, 60, 120 and 240 days post infection (dpi). During the acute phase of infection at 30 dpi, the host immune response was most notable demonstrating an up-regulation of several cytokines in reproductive tissues, including the epididymus (IL-6, IL-1ß and IL-1α), testicles (INF-γ and IL-12), bulbourethral glands (IL-6 and TNF-α) and ampolae (INF-γ, IL-10, IL-1ß and IL-1α). During the development of infection, cytokine gene expression levels decreased, providing evidence of immunosuppression and evidence of immune evasion that favoured persistence of chronic R-B. ovis infection. During the chronic phase of R-B. ovis infection (120 and 240 dpi), cytokine production was down-regulated in the epididymus (IL-1ß and IL-1α), testicles (INF-γ and IL-12), and ampolae (INF-γ, IL-10, IL-1ß and IL-1α), with the exception of the bulbourethral glands (IL-6 and TNF-α) and epididymus (IL-6); in these tissues, R-B. ovis infection resulted in up-regulation of the pro-inflammatory cytokine IL-6. Herein, we report cytokine expression profiles in tissues of rams experimentally infected with the rough strain of B. ovis, which are associated with bacterial persistence and macrophage activation.

Association study and expression analysis of CD9 as candidate gene for boar sperm quality and fertility traits.

Cluster-of-differentiation antigen 9 (CD9) gene expressed in the male germ line stem cells is crucial for sperm-egg fusion, and was therefore selected as candidate gene for boar semen quality. The association of CD9 with boar sperm quality and fertility trait was analyzed using a total of 340 boars both from purebred Pietrain and Pietrain×Hampshire crosses. A single nucleotide polymorphism (g.358A>T) in intron 6 was significantly associated with sperm motility (MOT) (P<0.001), plasma droplet rate (PDR) (P<0.001) and abnormal spermatozoa rate (ASR) (P<0.01). Boars were divided into two groups with group 1 (G-I) boars having a higher SCON and SMOT, lower SVOL (sperm volume) and group 2 (G-II) having a lower SCON and SMOT, higher SVOL. The mRNA and protein expression levels were evaluated in reproductive, non-reproductive tissues and spermatozoa from G-I and G-II animals by using quantitative real-time PCR and western blotting. When both reproductive and non-reproductive tissues were examined, highest mRNA was expressed in prostate gland, then in the body of the epididymis, vas deferens and tail of the epididymis. In case of reproductive tissues, CD9 expression was higher in tissues and spermatozoa collected from G-I boars than those collected from G-II boars. The mRNA expression was significantly different (P<0.05) in body of epididymis from G-I and G-II boars. The CD9 protein expression results from western blot were coincided with the results of qRT-PCR. Moreover, CD9 protein localization in Leydig cells, Sertoli cells, epithelial cells and spermatozoa was remarkable which indicated the important role of CD9 in spermatogenesis process. By using mRNA and protein expression profiles, it could be shown that CD9 plays a crucial role during sperm development, especially within the epididymis where the maturation of the sperm, a key process for the sperm quality and motility takes place. These results will improve the understanding of the functions of the CD9 in spermatogenesis within the reproductive tracts and will shed light on CD9 as a candidate gene in the selection of good sperm quality boars.

Expression of toll-like receptors in genital tract tissues from normal and HIV-infected men.

PROBLEM: cells of the innate immune system use Toll-like receptors (TLRs) to recognize and respond to invading pathogens. This study was carried out to characterize TLR expression in the human male genital tract, an initial infection site for several sexually transmitted pathogens. METHOD OF STUDY: immunohistochemistry was used to detect expression of TLRs 1-9 in genital tract tissues from HIV(-) and HIV(+) men. RESULTS: in HIV(-) men, TLR1(+) leukocytes were detected throughout the genital tract. Leukocytes in the penile urethra also expressed TLRs2, 3, 5, 7 and 9. Epithelial cells in most tissues did not express TLRs; exceptions were the prostate, where TLRs3 and 8 were observed on the apical surface of luminal epithelial cells, and the penile urethra, where epithelial cells expressed TLR9. In genital tissues from HIV(+) men with AIDS, few TLR(+) cells were detected. CONCLUSION: cells in the male genital tract can express a variety of TLRs. The penile urethra contained the highest number of TLR(+) cells, indicating that this tissue plays a major role in the innate immune defense of the male genital tract. Overall, TLR expression was reduced in genital tissues from HIV(+) men.

Altered expression of cytokines and sex steroid receptors in the reproductive tract of cysticercotic male mice.

Infection with Taenia crassiceps cysticerci in male mice produces an increase in serum oestradiol levels, whereas serum testosterone is abolished. Concomitantly, complete atrophy of the reproductive tract of infected male mice is observed. The present study was undertaken to determine the expression pattern of cytokines involved in steroidogenesis and sex steroid receptors in the reproductive tissues of normal and infected male mice, and relating this expression pattern to whole parasite counts, serum sex steroid levels and pathology of the reproductive tract in infected male mice. The expression of IL-4, IFN-gamma and TNF-alpha in testes and seminal vesicles was markedly increased in infected mice; however, IL-10 and IL-1beta expression was importantly decreased in the same organs. IL-2 expression in reproductive tissues was not affected by infection. The infection markedly induced the expression of androgen receptor, in both reproductive organs tested, while subtypes of oestrogen receptors were decreased in both tissues.

Constitutive expression of the antibacterial CXC chemokine GCP-2/CXCL6 by epithelial cells of the male reproductive tract.

The reproductive tract is continuously challenged by potential pathogens present in the environment. Therefore, robust host defense mechanisms are essential both for the health of the individual and for fertilization. Antibiotic innate immunity peptides possess broad antimicrobial activity. Recently, we found that the CXC chemokine, granulocyte chemotactic protein (GCP)-2/CXCL6, possesses antibacterial activity. In the present study, we investigated, therefore, the presence of GCP-2/CXCL6 in the human male reproductive system. GCP-2/CXCL6 was detected at 19nM (mean; range: 5-47nM; n=14) in seminal plasma of fertile donors, i.e. at levels more than 100 times higher than those previously reported for the related chemokine IL-8/CXCL8. No GCP-2/CXCL6 could be detected in blood plasma of healthy donors, indicating local production in the male reproductive tract. In vasectomized donors, significantly lower levels of GCP-2/CXCL6 were found (mean: 3nM; range 2-7nM; n=7), demonstrating that the testis and epididymis contribute significantly to the GCP-2/CXCL6 content of seminal plasma. Strong expression of GCP-2/CXCL6 was found in the epithelium of the testis, epididymis and seminal vesicles, while the prostate epithelium showed weak expression, as determined by immunohistochemistry. A biological function is suggested, viz. at concentrations of the order of those found in seminal plasma, GCP-2/CXCL6 has antibacterial activity against the urogenital pathogen Neisseria gonorrhoeae. GCP-2/CXCL6 in seminal plasma may play roles in both host defense of the male urogenital tract and during fertilization.

The antibacterial chemokine MIG/CXCL9 is constitutively expressed in epithelial cells of the male urogenital tract and is present in seminal plasma.

The integrity of the urogenital tract against potentially invasive pathogens is important for the health of the individual, fertilization, and continuance of species. Antibiotic peptides with broad antimicrobial activity, among them chemokines, are part of the innate immune system. We investigated the presence of the antibacterial interferon (IFN)-dependent CXC chemokines, MIG/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11, in the human male reproductive system. MIG/CXCL9 was detected at 25.0 nM (range 8.1-40.6 nM; n = 14), whereas IP-10/CXCL10 and I-TAC/CXCL11 were detected at lower levels (mean 1.8 nM, range 0.3-5.8 nM and mean 0.6, 0.2-1.6 nM, respectively) in seminal plasma of fertile donors. The levels of MIG/CXCL9 are more than 300-fold higher than those previously reported in blood plasma. In vasectomized donors, significantly lower levels of MIG/CXCL9 (mean 14.7 nM, range 6.6-21.8) were found, suggesting that the testis and epididymis, in addition to the prostate, significantly contribute to the MIG/CXCL9 content of seminal plasma. Strong expression of MIG/CXCL9 was found in the epithelium of testis, epididymis, and prostate, as detected by immunohistochemistry. MIG/CXCL9 at concentrations in the order of those found in seminal plasma possessed antibacterial activity against the urogenital pathogen Neisseria gonorrhoeae. The relatively high levels of MIG/CXCL9 in seminal plasma point to roles for this chemokine in both host defense of the male urogenital tract and during fertilization.

Expression of bisecting type and Lewisx/Lewisy terminated N-glycans on human sperm.

Human sperm lack major histocompatibility class I molecules, making them susceptible to lysis by natural killer (NK) cells. Major histocompatibility class I negative tumor cells block NK cell lysis by expressing sufficient amounts of bisecting type N-glycans on their surfaces. Therefore, sperm could employ the same strategy to evade NK cell lysis. The total N-glycans derived from sperm were sequenced using ultrasensitive mass spectrometric and conventional approaches. Three major classes of N-glycans were detected, (i) high mannose, (ii) biantennary bisecting type, and (iii) biantennary, triantennary, and tetraantennary oligosaccharides terminated with Lewisx and Lewisy sequences. Immunostaining of normal sperm showed that glycoproteins bearing Lewisy sequences are localized to the acrosome and not the plasma membrane. In contrast, defective sperm showed distinct surface labeling with anti-Lewisy antibody. The substantial expression of high mannose and complex type N-glycans terminated with Lewisx and Lewisy sequences suggests that sperm glycoproteins are highly decorated with ligands for DC-SIGN. Based on previous studies, the addition of such carbohydrate signals should inhibit antigen-specific responses directed against sperm glycoproteins in both the male and female reproductive systems. Thus, the major N-glycans of human sperm are associated with the inhibition of both innate and adaptive immune responses. These results provide more support for the eutherian fetoembryonic defense system hypothesis that links the expression of carbohydrate functional groups to the protection of gametes and the developing human in utero. This study also highlights the usefulness of glycomic profiling for revealing potential physiological functions of glycans expressed in specific cell types.

Biochemical property and immunogenicity of mouse male reproductive tract CD52 (mrt-CD52).

Male reproductive tract CD52 (mrt-CD52) is known to be a pathogenic antigen for immunological infertility. Although human CD52 has been extensively investigated, the properties of mouse CD52 are not well elucidated. This study was conducted, therefore, to examine the tissue distribution, molecular composition and immunogenicity of mouse mrt-CD52. Immunohistological studies with an antibody to a synthetic peptide showed that mouse CD52 was localized mainly in the cauda epididymis and vas deferens, but not in the testis, liver, kidney or spleen. The molecule was composed of Asn (N)-linked and The/Ser (O)-linked carbohydrates as well as a glycosylphosphatidyl (GPI) anchor portion. Purified mrt-CD52 preparations produced antibodies by subcutaneous and intranasal immunization in both male and female mice. These antisera showed sperm-immobilizing activities with complement to mouse sperm. The research indicated mouse CD52 had similar biochemical and immunological properties to human CD52. This animal experiment is a good model for investigating human mrt-CD52 antibody detected in infertile patients.

Migration of mouse antibody-secreting hybridoma cells from blood to genital tract and its regulation by sex hormones are associated with the differential expression patterns of adhesion molecules and chemokines in the tract rather than in the antibody-secreting cells.

To understand better the molecular mechanisms of differential migration of antibody-secreting cells (ASCs) into mouse genital tracts, and regulation by sex hormones, surface markers, hormone receptors and adhesion molecules in mouse SG2 and PA4 hybridoma cells, respectively, secreting IgG2b and polymeric IgA antibody were detected by flow cytometry or RT-PCR. Semi-quantitative RT-PCR was also used for measuring mRNA expression of adhesion molecules and chemokines (VCAM-1, ICAM-1, P-selectin, JAM-1 and CXCL12) in genital tracts of various adult mouse groups. The mRNAs of androgen receptor, estrogen receptor beta and CXCR4 were expressed in the ASCs. Sex hormones had no effect on expression of these molecules in ASCs. Except for VCAM-1, mRNA of all examined genes was expressed in normal mouse genital tracts. The mean of relative amounts of ICAM-1 and CXCL12 mRNA in all examined organs of females were higher (2.1- and 1.9-fold) than those in males. After orchiectomy or ovariectomy, the expression of ICAM-1, CXCL12 and P-selectin mRNA in the examined organs increased, except JAM-1 in male and CXCL12 in female. Sex hormone treatment recovered the changes to normal levels of mRNA expression in many examined genital tissues. In combination with our previous work, preferential migration of ASCs into female genital tract and regulation of migration by sex hormones are associated with expression patterns of adhesion molecules and chemokines in genital tract rather than in ASCs.

Experimental autoimmune prostatitis: dihydrotestosterone influence over the immune response.

PURPOSE: In experimental autoimmune prostatitis in a rat model of chronic prostatic inflammation of noninfectious origin the prostatic 5alpha-dihydrotestosterone (DHT) concentration decreases because of depressed 5alpha-reductase activity. This decrease in androgens in situ could favor the development of autoimmune status at the same time. We noted that a DHT increase could protect the gland from immune aggression and/or its consequences in regard to prostatic androgenic metabolism. MATERIALS AND METHODS: We analyzed in vitro the (3H)-DHT enzymatic bioconversion of prostate homogenates of male accessory sexual gland extract (MAG) immunized rats and MAG immunized plus DHT implanted rats (DSG rats), and performed ventral prostate histological observations. The specific cell immune response against MAG antigen(s) was studied by delayed type hypersensitivity. RESULTS: In DSG and MAG rats, and controls enzymatic activities (3alpha/3beta-hydroxysteroid oxidoreductases) were 112.7 +/- 11.3, 91.4 +/- 15.0 (not significant) and 147.0 +/- 12.8 pmol per minute per mg protein (p <0.025). Histological findings in DSG rat ventral prostates revealed infiltrating mononuclear cell foci in lower quantity and less magnitude than in MAG rat prostates. Delayed type hypersensitivity values were positive in MAG rats and lower in DSG rats in relation to kidney treated and untreated rats. CONCLUSIONS: Results suggest that constantly elevated DHT levels could decrease the cell immune response but not at significantly. In contrast, androgenic metabolism remains altered in the presence of exogenous androgens.

A male genital tract-specific carbohydrate epitope on human CD52: implications for immunocontraception.

The identification of unique sperm surface epitopes that are not expressed or exposed in the female reproductive tract is a key element in the development of antibody-based contraceptives. Western blotting and immunohistochemistry were performed to define the tissue distribution of the S19 epitope, which has been proposed as a target for immunocontraception. S19 is an IgG1 murine monoclonal antibody (mAb) directed to an N-linked carbohydrate epitope on a 15-25 kDa glycoprotein, sperm agglutination antigen-1 (SAGA-1), containing a peptide core identical to that of the lymphocytic surface protein CD52. In this study, the S19 epitope was shown to be absent from human lymphocytes, demonstrating a distinction between this epitope and the CAMPATH epitope that is recognized by an antibody against the terminal tripeptide and GPI-anchor of CD52. Further tissue specificity analysis identified the S19 epitope in the epithelium of the human epididymis and vas deferens, as well as on both epididymal and ejaculated spermatozoa. In contrast, the S19 epitope was absent in the five human female reproductive tract and 18 other somatic tissues tested. These results support the use of the S19 epitope as a contraceptive immunogen and the suitability of the S19 mAb as an intravaginal contraceptive. To test the agglutinating activity of the S19 mAb in a formulation designed for vaginal use, S19 mAb were bound to the surface of Novasomes, a multilamellar liposome delivery vehicle. S19-Novasome formulations agglutinated human spermatozoa and were as effective as unbound S19 mAb, demonstrating the feasibility of spermistatic contraceptives targeted to the male reproductive tract specific carbohydrate epitope.

Circulating immunoglobulin A- and immunoglobulin G-secreting hybridoma cells in peripheral blood preferably migrate to female genital tracts. The role of sex hormones.

Antigen-specific circulating immunoglobulin-secreting cells (ISC) migrate to various secondary and tertiary lymphoid tissues. To understand the migration of the cells into the genital tract and its regulation by sex hormones, spleen-derived SG2 hybridoma cells secreting immunoglobulin G2b (IgG2b) and Peyer's patch-derived PA4 hybridoma cells secreting polymer IgA were labelled with 3H-TdR, and intravenously injected into syngeneic mice of both sexes. Using flow cytometry, surface molecular markers of plasma cells, CD38 and CD138, and adhesion molecules, CD49d, CD162, and CD11a were found to be positive in SG2 and PA4 cells, but CD62L, alpha4beta7 and CD44 were not expressed on these cells. The relative distribution indexes (RDIs) of the cells in genital tract and other tissues were measured. The means of RDIs of SG2 and PA4 cells in female genital tissues were 6.5 and 4.5 times as many as the means in male genital tissues, respectively. The treatment of ovariectomized mice with beta-oestradiol significantly increased the RDIs of PA4 cells in cervix and vagina, but decreased the RDIs of SG2 cells in vagina, horn of uterus, uterus and rectum (P<0.05). Progesterone treatment increased the RDIs of PA4 cells in vagina and rectum (P<0.05). The treatment with testosterone significantly increased the RDIs of SG2 and PA4 cells in epididymis and accessory sex glands (P<0.05). These results demonstrate that the female genital tract is the preferable site for the migration of circulating hybridoma cells to the male genital tract, and sex hormones play an important role in regulation of the migration of circulating ISC to genital tracts.

[Progresses on macrophages of male reproductive tract].

The review summarized the recent progress on macrophages of male reproductive tract and the action of macrophages on male reproductive physiology and pathology. The close correlation and effect between testicular macrophages and Leydig cells, Sertoli cells, germ cells, hypothalamic-pituitary-gonadal axis were introduced, respectively. At the same time, it pointed out the changes of macrophages' morphology and function in immune orchitis, and their regulation on the development of orchitis. So the complex immune regulation network in testes and testicular macrophages playing an important role on spermatogenesis and the stableness of spermatogenetic microenvironment in testes were further illuminated, which can provide theoretical basis for clinic therapy.