242. LIF expression is induced in the mouse oviduct following activation by seminal factors

Advances in Experimental Medicine and Biology

2015

Carriage of sperm is not the only function of seminal fluid in mammals. Studies in mice show that at conception, seminal fluid interacts with the female reproductive tract to induce responses which influence whether or not pregnancy will occur, and to set in train effects that help shape subsequent fetal development. In particular, seminal fluid initiates female immune adaptation processes required to tolerate male transplantation antigens present in seminal fluid and inherited by the conceptus. A tolerogenic immune environment to facilitate pregnancy depends on regulatory T cells (Treg cells), which recognise male antigens and function to suppress inflammation and immune rejection responses. The female response to seminal fluid stimulates the generation of Treg cells that protect the conceptus from inflammatory damage, to support implantation and placental development. Seminal fluid also elicits molecular and cellular changes in the oviduct and endometrium that directly promote embryo development and implantation competence. The plasma fraction of seminal fluid plays a key role in this process with soluble factors, including TGFB, prostaglandin-E, and TLR4 ligands, demonstrated to contribute to the peri-conception immune environment. Recent studies show that conception in the absence of seminal plasma in mice impairs embryo development and alters fetal development to impact the phenotype of offspring, with adverse effects on adult metabolic function particularly in males. This review summarises our current understanding of the molecular responses to seminal fluid and how this contributes to the establishment of pregnancy, generation of an immune-regulatory environment and programming long-term offspring health.

Section: Seminal Fluid and The Peri-conception Infl Ammatory Responsementioning

confidence: 98%

Seminal Fluid Signalling in the Female Reproductive Tract: Implications for Reproductive Success and Offspring Health

Schjenken

Advances in Experimental Medicine and Biology

2015

“…[47][48][49] Other embryotrophic cytokines follow the same pattern of synthesis, including LIF, IL6 and several chemokines. 50,51 The importance of seminal fluid signalling as a regulator of female tract cytokines is indicated by experiments in mice, other rodents and pigs. 52,53 When pregnancy is initiated by mating with males from which the seminal vesicles are surgically removed to ablate the seminal stimulus, the proportion of mated females achieving pregnancy is reduced substantially.…”

Section: Regulation Of Cytokines In the Oviduct And Uterusmentioning

confidence: 99%

Peri‐Conceptual Cytokines – Setting the Trajectory for Embryo Implantation, Pregnancy and Beyond

Chin

Glynn

et al. 2011

American J Rep Immunol

Citation Robertson SA, Chin PY, Glynn DJ, Thompson JG. Peri‐Conceptual Cytokines – Setting the Trajectory for Embryo Implantation, Pregnancy and Beyond. Am J Reprod Immunol 2011; 66 (Suppl. 1): 2–10Problem The peri‐conceptual environment influences the early embryo to impart long‐term consequences for the fetus and neonate; however, the underlying mechanisms are not well defined.Method of Study We argue that the cytokine network acting in the female reproductive tract during the pre‐ and peri‐implantation period integrates environmental information to program the embryo and fine‐tune the maternal immune response and endometrial remodelling to determine implantation success.Results As well as sex steroid hormones and male seminal fluid factors, female tract cytokines are influenced by agents signalling via the Toll‐like receptors including the microbiome and a plethora of metabolic, chemical and other stressors. In mouse models, an altered peri‐conceptual cytokine environment induced by cytokine deficiency, inflammatory insults or dysregulated seminal fluid signalling is associated with adverse effects on embryo development, pregnancy viability and reproductive outcome.Conclusion The cytokine network provides a pivotal mechanism through which environmental factors influence both embryo development and receptivity of the uterus.

“…The extent to which this influences the events of implantation is likely to vary between species and the extent to which different components of seminal fluid access different regions of the tract. In mice, seminal fluid introduction into the uterus after mating induces production of a range of cytokines including LIF, IL6 and GM-CSF (Jasper et al, 2005, Tremellen et al, 1998) from estrogen-primed epithelial cells of the female reproductive tract. This results in the recruitment and activation of both innate and adaptive leukocytes, in an immune event that resembles a typical inflammatory cascade (Robertson, 2005.…”

Section: Cytokine and Leukocyte Regulation By Seminal Fluidmentioning

confidence: 99%

Immunological determinants of implantation success

Moldenhauer²

2014

Int. J. Dev. Biol.

108

The capacity of the immune system to maintain the integrity of the individual requires recognition and control of entities identified as genetically distinct, or 'non-self' . In mammalian reproduction, the embryo and subsequent fetus and placenta are all recognized as non-self by the maternal immune system, and are vulnerable to immunological attack. An active system to prevent rejection must exist from when conceptus and maternal tissues first come into contact at implantation.