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

  • John E. Schjenken
  • Sarah A. RobertsonEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 868)


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.


Seminal fluid Prostaglandin E Transforming growth factor-beta Natural killer cells Toll-like receptors Regulatory T cells Cytokines Maternal immune tolerance 



Artificial Insemination


Antimicrobial peptide


Antigen-presenting cells


Assisted reproductive technologies


Accessory sex glands


Bovine seminal plasma protein


C-C motif chemokine ligand


Cyclooxygenase 2


Cysteine-rich secretory protein-3


Colony-stimulating factor


C-X-C motif chemokine ligand


Danger-associated molecular patterns


Forkhead box P3


Granulocyte colony-stimulating factor


Granulocyte-macrophage colony-stimulating factor


Growth regulated alpha


Interferon gamma




In vitro fertilisation


Janus kinase/Signal transducer and activator of transcription


Leukaemia inhibitory factor


Mitogen-activated protein kinase


Monocyte chemotactic protein 1


Major histocompatibility complex


Macrophage inflammatory protein


Matrix metalloproteinase

NK cells

Natural killer cells


Ovulation-inducing factor


Phosphatidylinositol-3 kinase-protein kinase B


Prostaglandin E


Porcine sperm adhesion proteins


Soluble fms-like tyrosine kinase-1


Seminal vesicle deficient


Transforming growth factor beta


Tissue inhibitor of matrix metalloproteinase


Toll-like receptor


Tumor Necrosis Factor

Treg cells

Regulatory T cells


Vascular endothelial growth factor


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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Robinson Research InstituteUniversity of AdelaideAdelaideAustralia
  2. 2.School of Paediatrics and Reproductive HealthUniversity of AdelaideAdelaideAustralia

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