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Review
. 2025 Apr 17;35(1):14.
doi: 10.1186/s12610-025-00262-5.

Ureaplasma urealyticum upregulates seminal fluid leukocytes and lowers human semen quality: a systematic review and meta-analysis

Omotola SeunFunmi Kukoyi  1   2 , Victory Jesutoyosi Ashonibare  2   3 , Cecilia Adedeji Adegbola  2   4 , Tunmise Maryanne Akhigbe  2   5 , Roland Eghoghosoa Akhigbe  6   7
Affiliations
Review

Ureaplasma urealyticum upregulates seminal fluid leukocytes and lowers human semen quality: a systematic review and meta-analysis

Omotola SeunFunmi Kukoyi et al. Basic Clin Androl. .

Abstract
in English, French

Background: Ureaplasma urealyticum belongs to the class Mollicutes and causes non-gonococcal urethritis, an inflammation of the urethra that is linked with impaired semen quality. However, some reports are contradictory, and the reported effect of U. urealyticum on specific sperm variables is not consistent. Thus, this study synthesized findings from published primary data and provides a robust and reliable inference on the impact and associated mechanisms of U. urealyticum on sperm quality.

Methods: A systematic search was conducted until 31st May, 2024, on Cochrane, Google Scholar, and Pubmed. The Population, Exposure, Comparator/Comparison, Outcomes, and Study Design (PECOS) model was adopted. The populations were male in their reproductive ages who were infected with Ureaplasma urealyticum and confirmed positive versus the control who were age-matched non-infected or treated, while the outcomes included conventional semen parameters, seminal fluid leucocyte count, and sperm interleukin-6 (IL-6) concentrations, and the studies were either cross-sectional or longitudinal.

Results: When compared with the control, quantitative analysis demonstrated that U. urealyticum significantly reduced ejaculate volume (SMD 0.33 [95% CI: 0.15, 0.52] p = 0.0004), sperm concentration (SMD 0.47 [95% CI: 0.31, 0.64] p < 0.00001), total sperm motility (SMD 0.73 [95% CI: 0.43, 1.02] p < 0.00001), total motile sperm count (SMD 0.21 [95% CI: 0.17, 0.26] p < 0.00001), normal sperm morphology (SMD 0.88 [95% CI: 0.42, 1.35] p = 0.0002), but increased seminal fluid leukocyte count (SMD -0.82 [95% CI: -1.61, -0.02] p = 0.04). In addition, qualitative analysis revealed that U. urealyticum-positive subjects had significantly higher levels of IL-1β, IL-6, IL-8, TNF-α, peroxidase, leukocytes, neutrophils, CD4 + T cells, and CD8 + T cells in the seminal fluid when compared with the control. Furthermore, higher sperm DNA fragmentation and apoptotic sperm cells were observed in U. urealyticum-positive subjects when compared to the control.

Conclusions: These findings revealed that U. urealyticum lowers semen quality via the upregulation of seminal fluid leukocytes, elastase, pro-inflammatory cytokines, and DNA fragmentation. However, further studies are required to elucidate the mechanisms underlying the association between U. urealyticum and semen quality decline and to develop effective therapies for this condition.

RéSUMé: CONTEXTE: Ureaplasma urealyticum appartient à la classe des Mollicutes et provoque une urétrite non gonococcique, une inflammation de l’urètre, qui est liée à une altération de la qualité du sperme. Cependant, certains rapports sont contradictoires, et l’effet rapporté de U. urealyticum sur les paramètres spécifiques des spermatozoïdes n’est pas cohérent. La présente étude a synthétisé les résultats des données primaires publiées, et fournit une inférence robuste et fiable sur l’impact et les mécanismes associés d’U. urealyticum sur la qualité du sperme. Une recherche systématique a été menée jusqu’au 31 mai 2024 sur Cochrane, Google Scholar et PubMed. Le modèle PECOS (Population, Exposure, Comparator/Comparison, Outcomes, and Study Design) a été adopté. Les populations étaient des hommes en âge de procréer et infectés par U urealyticum, et dont les résultats positifs étaient confirmés par rapport aux témoins appariés selon l’âge, non infectés ou traités ; les résultats comprenaient les paramètres conventionnels du sperme, le nombre de leucocytes dans le liquide séminal et les concentrations d’interleukine-6 des spermatozoïdes (IL-6). RéSULTATS: Par rapport aux témoins, l’analyse quantitative a montré que U. urealyticum réduisait significativement le volume d’éjaculat (Différence de Moyenne Standardisée DMS 0,33 [IC à 95 % : 0,15, 0,52] p = 0,0004), la concentration de spermatozoïdes (DMS 0,47 [IC à 95 % : 0,31, 0,64] p< 0,00001), la motilité totale des spermatozoïdes (DMS 0,73 [IC à 95 % : 0,43, 1,02] p< 0,00001), le nombre total de spermatozoïdes mobiles (DMS 0,21 [IC à 95 % : 0,17, 0,26] p< 0,00001), les spermatozoïdes de morphologie normale (DMS 0,88 [IC à 95 % : 0,42, 1,35] p = 0,00002), mais augmentait la numération leucocytaire du liquide séminal (DMS -0,82 [IC à 95 % : -1,61, -0,02] p = 0,04). De plus, l’analyse qualitative a révélé que les sujets positifs à U. urealyticum présentaient des taux significativement plus élevés d’IL-1β, d’IL-6, d’IL-8, de TNF-α, de peroxydase, de leucocytes, de neutrophiles, de lymphocytes T CD4+ et de lymphocytes T CD8+ dans le liquide séminal par rapport aux témoins. De plus, des taux plus élevés de fragmentation de l’ADN des spermatozoïdes et de spermatozoïdes apoptotiques ont été observées chez les sujets positifs à U. urealyticum par rapport aux témoins. CONCLUSIONS: Ces résultats ont révélé que U. urealyticum abaisse la qualité du sperme via la régulation positive des leucocytes du liquide séminal, de l’élastase, des cytokines pro-inflammatoires et de la fragmentation de l’ADN. Cependant, d’autres études sont nécessaires pour élucider les mécanismes sous-jacents à l’association entre U. urealyticum et le déclin de la qualité du sperme, ainsi que pour développer des traitements efficaces pour cette maladie.

Keywords: Ureaplasma urealyticum; Immunology; Infection; Male infertility; Semen; Testosterone.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA flowchart for the strategic identification, screening, and inclusion of eligible studies
Fig. 2
Fig. 2
Effect of ureaplasma urealyticum on human ejaculate volume. UU: Ureaplasma urealyticum, SD: Standard deviation, CI: confidence interval. Meta-analysis was performed using a random-effect model. Data are shown as standardized mean difference and Confidence interval (CI)
Fig. 3
Fig. 3
Effect of ureaplasma urealyticum on seminal fluid pH. UU: Ureaplasma urealyticum, SD: Standard deviation, CI: confidence interval. Meta-analysis was performed using a random-effect model. Data are shown as standardized mean difference and Confidence interval (CI)
Fig. 4
Fig. 4
Effect of ureaplasma urealyticum on sperm concentration. UU: Ureaplasma urealyticum, SD: Standard deviation, CI: confidence interval. Meta-analysis was performed using a random-effect model when p-value < 0.1 or I.2 > 50%; otherwise, a fixed-model effect is used. Data are shown as standardized mean difference and Confidence interval (CI)
Fig. 5
Fig. 5
Effect of ureaplasma urealyticum on sperm total motility. UU: Ureaplasma urealyticum, SD: Standard deviation, CI: confidence interval. Meta-analysis was performed using a random-effect model. Data are shown as standardized mean difference and Confidence interval (CI)
Fig. 6
Fig. 6
Effect of ureaplasma urealyticum on sperm progressive motility. UU: Ureaplasma urealyticum, SD: Standard deviation, CI: confidence interval. Meta-analysis was performed using a random-effect model. Data are shown as standardized mean difference and Confidence interval (CI)
Fig. 7
Fig. 7
Effect of ureaplasma urealyticum on total motile sperm count. UU: Ureaplasma urealyticum, SD: Standard deviation, CI: confidence interval. Meta-analysis was performed using a random-effect model when p-value < 0.1 or I.2 > 50%; otherwise, a fixed-model effect is used. Data are shown as standardized mean difference and Confidence interval (CI)
Fig. 8
Fig. 8
Effect of ureaplasma urealyticum on sperm vitality. UU: Ureaplasma urealyticum, SD: Standard deviation, CI: confidence interval. Meta-analysis was performed using a random-effect model. Data are shown as standardized mean difference and Confidence interval (CI)
Fig. 9
Fig. 9
Effect of ureaplasma urealyticum on normal sperm morphology. UU: Ureaplasma urealyticum, SD: Standard deviation, CI: confidence interval. Meta-analysis was performed using a random-effect model when p-value < 0.1 or I.2 > 50%; otherwise, a fixed-model effect is used. Data are shown as standardized mean difference and Confidence interval (CI)
Fig. 10
Fig. 10
Effect of ureaplasma urealyticum on seminal fluid leukocyte count. UU: Ureaplasma urealyticum, SD: Standard deviation, CI: confidence interval. Meta-analysis was performed using a random-effect model. Data are shown as standardized mean difference and Confidence interval (CI)
Fig. 11
Fig. 11
Effect of ureaplasma urealyticum on seminal fluid IL- 6. UU: Ureaplasma urealyticum, SD: Standard deviation, CI: confidence interval. Meta-analysis was performed using a random-effect model. Data are shown as standardized mean difference and Confidence interval (CI)
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