Seminal Plasma Regulates Female Reproductive Function: A Narrative Review

Objectives: This review aimed to elucidate the physiological roles of seminal plasma (SP) in modulating female reproductive function, with an emphasis on the mechanisms that optimize the conception microenvironment. Moreover, this review further evaluated the translational potential of SP as an adjunct to assisted reproductive technologies (ARTs). Mechanisms: 1. Molecular signaling: SP acted as both a transport medium for spermatozoa and a carrier of male-derived bioactive molecules (e.g., transforming growth factor-β (TGF-β), prostaglandins) that activated Toll-like receptor (TLR)-mediated signaling pathways in female reproductive tissues; 2. Immune modulation: SP triggered a transient inflammatory response in the cervicovaginal mucosa, enhancing pathogen clearance capacity by upregulating neutrophil recruitment and antimicrobial peptide secretion; 3. Receptivity regulation: SP components (particularly extracellular vesicles) modified endometrial epithelial-stromal crosstalk via paracrine interactions, extending the implantation window by modulating Homeobox A10 (HOXA10) expression. 4. Maternal-fetal tolerance: SP-induced regulatory T cell expansion promoted immune acceptance of semi-allogeneic embryos by suppressing Th1/Th17 responses at the decidual interface. Findings in Brief: Exposure to SP induced a self-limiting inflammatory cascade that optimized sperm survival and endometrial preparedness in murine and human studies. ART cycles incorporating SP perfusion demonstrated a 14.4% increase in clinical pregnancy rates (pooled odds ratio [OR] = 1.32, 95% confidence interval [CI]: 1.08–1.61) across eight randomized trials. Proteomic analyses identified SP exosomes as critical mediators of endometrial receptivity, though batch variability remained a translational challenge. Conclusions: SP emerged as a master regulator of peri-conception events through multimodal mechanisms. While preclinical data supported its therapeutic utility in recurrent implantation failure (RIF), standardized protocols for clinical deployment required further validation. Future research should prioritize the mechanistic dissection of exosome-carried microRNAs and large-scale studies of ART outcomes.