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

  • Chapter
The Male Role in Pregnancy Loss and Embryo Implantation Failure

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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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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Authors and Affiliations

  1. Robinson Research Institute, University of Adelaide, Adelaide, SA, 5005, Australia

    John E. Schjenken & Sarah A. Robertson

  2. School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, 5005, Australia

    John E. Schjenken & Sarah A. Robertson

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  1. John E. Schjenken
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  1. Obstetrics, Gynecology, & Repro Medicine, Stony Brook University Medical Center T9-080, Stony Brook, New York, USA

    Richard Bronson

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Schjenken, J.E., Robertson, S.A. (2015). Seminal Fluid Signalling in the Female Reproductive Tract: Implications for Reproductive Success and Offspring Health. In: Bronson, R. (eds) The Male Role in Pregnancy Loss and Embryo Implantation Failure. Advances in Experimental Medicine and Biology, vol 868. Springer, Cham. https://doi.org/10.1007/978-3-319-18881-2_6

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