Transforming growth factor β—a mediator of immune deviation in seminal plasma

Robertson, Sarah A.; Ingman, Wendy V.; O’Leary, Seán; Sharkey, David J.; Tremellen, Kelton

doi:10.1016/s0165-0378(02)00015-3

Cited by 242 publications

(199 citation statements)

References 46 publications

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“…In conclusion, the PSP-I/PSP-II at relatively low concentrations is a post-mating (or post-AI) inflammatory mediator in pigs. Since T cells generally take several days to generate a robust response after stimulation, longer periods are needed, but might be difficult to obtain using in vivo protocols.The SP of the boar contains immune-regulatory molecules, including high concentrations of the potent immunosuppressive transforming growth factor-β (TGF-β) multifunctional cytokine group (Robertson et al, 2002), which, mediated by Treg (in rodents), induce differentiation of suppressor T cell phenotypes, to reach a state of adaptative functional immune tolerance to male antigens by the female (O'Leary et al, 2004;Robertson et al, 2006Robertson et al, , 2009Robertson, 2007), most relevant to early pregnancy and, further, to fertility. The SP from different boars varies largely in its contents of cytokines, which in turn leads to differential expression of endogenous cytokines in the females (Robertson, 2007).…”

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confidence: 99%

Spermadhesin PSP-I/PSP-II heterodimer induces migration of polymorphonuclear neutrophils into the uterine cavity of the sow

Rodriguez‐Martinez

Saravia

Wallgren

et al. 2010

Journal of Reproductive Immunology

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This is an author produced version of a paper published in Journal of Reproductive Immunology. This paper has been peer-reviewed and is proof-corrected, but does not include the journal pagination.Citation for the published paper: Rodriguez-Martinez, H., et al. AbstractThe heterogeneous seminal plasma (SP) is involved in endometrial inflammation and following immune changes that occur post-mating in pigs. This study tested whether SP spermadhesins (binding heparin [HBPs] or not [PSP-I/PSP-II]) recruit different lymphocyte subsets (CD2 + , CD4 + and CD8 + ) and polymorphonuclear leukocytes (PMNs) to the superficial endometrium/lining epithelium and lumen, respectively, of oestrous sows, in vivo. In Experiment 1, endometrial biopsies were taken under narcosis from six sows whose uterine horns were separated and their lumen infused with 3 mg/mL spermadhesins (HBP resp PSP-I/PSP-II) in 100 mL saline (treatment horn) or 100 mL saline (control horn). Endometrial samples removed between 2 and 120 min post-infusion were studied by immunohistochemistry (IHC, using mABs) or histology, to assess the degree of T-cell respectively PMN entry over time. In Experiment 2, eight conscious oestrous sows were singly infused intra-utero with 3 mg/mL of PSP-I/PSP-II in 100 mL saline (n = 4) or 100 mL of saline (n = 4), to assess relative PMN numbers in the uterine lumen, 3 h post-infusion.Compared to controls, PSP-I/PSP-II infusion significantly recruited uterine lymphocytes from 10 min (CD2 + ) or from 60 min (CD8 + ) onwards, while HBPs had only increased CD4 + cells by 120 min. As well, PSP-I/PSP-II, but not HBPs, significantly (P < 0.05) induced an early (10 min) PMN migration to the surface epithelium, 5-fold by 30 min and 7-fold from 60 min onwards (P < 0.001), with PMNs visible in the lumen from 30 min of infusion. Six-fold more PMNs were collected from the uterine lumen of PSP-I/PSP-II-infused sows compared to controls, 3 h after infusion (P < 0.001). Seminal plasma PSP-I/PSP-II heterodimer triggers the entry of cleansing uterine PMNs, initiating a cascade of transient and long-lasting immunological events in oestrous sows. IntroductionIn the pig, as in many other species, mating causes a transient endometrial inflammation (reviewed by Robertson et al., 2006) which, at first sight, is a logical step by the female genital tract to combat the entry of foreign cells (e.g. the spermatozoa), foreign proteins (in the seminal plasma, SP) and, eventually, of pathogens. Some spermatozoa escape this inflammation by reaching the oviductal sperm reservoir (SR) and participating in fertilization.Spermatozoa, and later the early embryo, the foetus and the placenta, are immuno-tolerated by HRM et al-2009-BSP as uterine immunoattractants the female, despite all being allogeneic (they contain transcripts of paternal origin) and thus liable to immune rejection. How is this accomplished?The boar ejaculate is large and fractionated; most spermatozoa are delivered in a sperm-rich fraction (SRF) followed by a post-SRF containing increasing am...

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confidence: 99%

Spermadhesin PSP-I/PSP-II heterodimer induces migration of polymorphonuclear neutrophils into the uterine cavity of the sow

Rodriguez‐Martinez

Saravia

Wallgren

et al. 2010

Journal of Reproductive Immunology

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“…The SP also contains prostaglandin E and TGF-β, capable of initiating tolerance towards foreign antigens [12]. These cytokines are likely to be important in skewing the T-cells towards the Treg cell subpopulation [16]. Exposure to SP on the day of the OPU may trigger the immune tolerance to the paternal antigens and thus improve the embryo implantation.…”

Section: Discussionmentioning

confidence: 99%

Seminal plasma insemination during ovum-pickup—a method to increase pregnancy rate in IVF/ICSI procedure. A pilot randomized trial

Chicea¹,

Ispasoiu²,

Focşa

2013

J Assist Reprod Genet

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Purpose In IVF procedures, endometrial function is a limiting factor of the pregnancy rate and the aims of this study is to determine whether seminal plasma insemination at ovum pick-up in IVF has any effect on pregnancy rate. Methods We designed a single center, 2 parallel groups, randomized pilot study. All couples undergoing an IVF procedure in our clinic between January 2010 and December 2011 were considered for enrollment in the study. The patients who met the inclusion criteria were randomized into two groups by simple randomization: the seminal plasma group (SP group) and the reference group (noSP group). We applied seminal plasma into the cervix and vaginal vault at the time of the OPU in the patients of the SP group. The primary outcome was the clinical pregnancy rate in the SP group compared with the noSP group and the secondary outcome measure was the implantation rate. Results 400 patients met the inclusion criteria and were randomized. 54 patients were excluded from the study mainly because they didn't undergo the embryo transfer. Finally, 164 patients were included in the SP group and 182 patients in the noSP group and analyzed. We found a statistically non-significant increase in the pregnancy rate in the SP group (55.5 % versus 44 %, p=0.09) and a statistically significant increase in the implantation rate (34.7 % versus 27.5 %, p=0.026). Conclusions Our results support the idea that SP insemination may have the potential to increase pregnancy rate in IVF procedures but further studies must be carried out.

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“…As a result, an inflammatory reaction is incited, characterized by a massive infiltration of neutrophils that are likely recruited by the high concentrations of IL-8 ( Table 1 and Supplementary Table S4) and GM-CSF ( Table 1 and Supplementary Table S5) found in seminal fluid [11]. The initial phase of inflammation is important to clear excess and abnormal sperm as well as various waste products found within semen [11,12]. It is vital, however, that the inflammatory phase be quickly resolved, as uncontrolled inflammation could lead to the clearance of the healthy sperm cells by neutrophils and result in a reduced capacity for fertilization.…”

Section: Factors In Semen Modulate Immunity Essential To Establishingmentioning

confidence: 99%

“…Another important suppressive component found in high concentrations is prostaglandin E 2 (PGE 2 ), which also originates in the seminal vesicles ( Table 1 and Supplementary Table S1). Prostaglandins are key in dampening the immune response through inhibition of macrophage cytokine production and T cell proliferation [11][12][13]17,18]. Like IL-15, PGE 2 also works in combination with TGF-β to promote tolerance of paternal and fetal antigens, contributing to the differentiation and expansion of T reg cells in the FRT [4,13].…”

Section: Factors In Semen Modulate Immunity Essential To Establishingmentioning

confidence: 99%

Variability in human semen content and its potential effects in the female reproductive tract

Keogan¹,

Siegert²,

Wigdahl³

et al. 2016

J Reprod Biol Health

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Human semen is a complex medium containing high concentrations of cytokines, chemokines, and growth factors that play key roles in orchestrating immune responses during reproduction. These factors are essential to establishing conditions that facilitate fertilization and embryogenesis through modulation of local immune responses in the female reproductive tract. Typically, semen initiates a biphasic process of inflammation that is gradually resolved, leading to immune cell recruitment pivotal to clearing excess sperm and establishing tolerance of the fetal allograft. However, the identity and concentration of factors found in semenmay be altered in the male reproductive tract as a consequence of sexually transmitted infections and infertility conditions. As a result, imbalances in semen content can skew the secretory response of the cervicovaginal epithelium after deposition during heterosexual intercourse, which may distort local immune activity and lead to embryo rejection or enhanced pathogen transmission. Recognizing the array of factors contained in semen and the degree to which they vary is an essential part of understanding the impact of variations in semen content on reproductive biology and the transmission of sexually transmitted disease pathogens.

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Transforming growth factor β—a mediator of immune deviation in seminal plasma

Cited by 242 publications

References 46 publications

Spermadhesin PSP-I/PSP-II heterodimer induces migration of polymorphonuclear neutrophils into the uterine cavity of the sow

Spermadhesin PSP-I/PSP-II heterodimer induces migration of polymorphonuclear neutrophils into the uterine cavity of the sow

Seminal plasma insemination during ovum-pickup—a method to increase pregnancy rate in IVF/ICSI procedure. A pilot randomized trial

Variability in human semen content and its potential effects in the female reproductive tract

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