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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)

Abstract

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.

Keywords

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

Abbreviations

AI

Artificial Insemination

AMP

Antimicrobial peptide

APC

Antigen-presenting cells

ART

Assisted reproductive technologies

ASG

Accessory sex glands

BSP

Bovine seminal plasma protein

CCL

C-C motif chemokine ligand

COX2

Cyclooxygenase 2

CRISP3

Cysteine-rich secretory protein-3

CSF

Colony-stimulating factor

CXCL

C-X-C motif chemokine ligand

DAMP

Danger-associated molecular patterns

FOXP3

Forkhead box P3

GCSF

Granulocyte colony-stimulating factor

GMCSF

Granulocyte-macrophage colony-stimulating factor

GRO/KC

Growth regulated alpha

IFNG

Interferon gamma

IL

Interleukin

IVF

In vitro fertilisation

JAK/STAT

Janus kinase/Signal transducer and activator of transcription

LIF

Leukaemia inhibitory factor

MAPK

Mitogen-activated protein kinase

MCP1

Monocyte chemotactic protein 1

MHC

Major histocompatibility complex

MIP

Macrophage inflammatory protein

MMP

Matrix metalloproteinase

NK cells

Natural killer cells

OIF

Ovulation-inducing factor

P13K-AKT

Phosphatidylinositol-3 kinase-protein kinase B

PGE

Prostaglandin E

PSP

Porcine sperm adhesion proteins

sFlt1

Soluble fms-like tyrosine kinase-1

SVX

Seminal vesicle deficient

TGFB

Transforming growth factor beta

TIMP

Tissue inhibitor of matrix metalloproteinase

TLR

Toll-like receptor

TNF

Tumor Necrosis Factor

Treg cells

Regulatory T cells

VEGF

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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