Seminal Plasma Influence on Female Reproductive Immunity

Seminal plasma, the fluid component of semen rich in proteins, lipids and signalling molecules, plays a pivotal role in shaping the female reproductive immune landscape. Immediately after insemination, seminal plasma initiates a controlled inflammatory response characterised by transient cytokine release and neutrophil recruitment. This early reaction serves to clear pathogens and cellular debris without compromising tissue integrity. Subsequently, immunoregulatory factors within seminal plasma promote tolerance by expanding regulatory T cells and modulating dendritic cell function, thereby facilitating endometrial decidualisation and embryo implantation. Beyond its physiological impact, seminal plasma can influence susceptibility to sexually transmitted infections through direct antimicrobial effects or by altering mucosal barrier function. Conversely, aberrant seminal plasma composition—whether due to advanced paternal age, infection or metabolic disorders—can disrupt these finely tuned immune adaptations, contributing to implantation failure, pregnancy complications and suboptimal assisted reproduction outcomes. Understanding these mechanisms has global implications for fertility therapies, vaccine design against sexually transmitted pathogens and the improvement of assisted conception protocols.

Research from Nature Portfolio

Seminal plasma has been shown to inhibit infection by Chlamydia trachomatis in vitro, with dose-dependent suppression of epithelial cytokine production and alteration of neutrophil activation, reactive oxygen species generation and phagocytic capacity. This work highlights the importance of including seminal plasma factors when modelling mucosal immunity and pathogen transmission in the female reproductive tract. In murine models, mating with intact males induces uterine expression of pro-inflammatory and regulatory cytokines via Toll-like receptor-4-dependent signalling. Sperm-derived signals recruit neutrophils and expand peripheral regulatory T cells, demonstrating a synergistic role for sperm and seminal plasma in promoting immune tolerance essential for embryo implantation and reproductive success.

Seminal Plasma Influence on Female Reproductive Immunity publication trend

The graph below shows the total number of articles in seminal plasma influence on female reproductive immunity across all publications each year (not limited to Nature Index journals).

Technical terms

Seminal plasma: Fluid fraction of semen containing nutrients, cytokines and immunomodulatory factors.

Cytokine: Small protein secreted by cells that mediates and regulates immunity, inflammation and haemopoiesis.

Toll-like receptor (TLR): Pattern-recognition receptor on immune and epithelial cells that detects pathogen-associated molecular patterns and triggers inflammatory signalling.

Regulatory T cell (Treg): Subset of T lymphocytes that suppress immune activation and maintain tolerance to self and alloantigens.

Decidualisation: Process by which endometrial stromal cells transform into specialised secretory cells to support embryo implantation.

References

1. Sperm activate TLR2/TLR1 heterodimerization to induce a weak proinflammatory response in the bovine uterus. Frontiers in Immunology (2023).
2. Intravaginal exposure to seminal plasma after ovum pick-up does not increase live birth rates after in vitro fertilization or intracytoplasmic sperm injection treatment: a double-blind, placebo-controlled randomized trial. Fertility and Sterility (2024).
3. Immune Regulation of Seminal Plasma on the Endometrial Microenvironment: Physiological and Pathological Conditions. International Journal of Molecular Sciences (2023).
4. Seminal plasma inhibits Chlamydia trachomatis infection in vitro, and may have consequences on mucosal immunity. Scientific Reports (2024).
5. Sperm modulate uterine immune parameters relevant to embryo implantation and reproductive success in mice. Communications Biology (2021).