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Meta-Analysis
. 2025 Jan-Feb;19(1):15579883251319134.
doi: 10.1177/15579883251319134.

Association of ESR1 Xba1 (rs9340799) With Male Infertility: A Systematic Review and Meta-Analysis

Hania Qamar  1 , Sadia Bibi  1 , Zeeshan Qadeer  2 , Faiza Muzammil  1 , Masooma Batool  1 , Shaista Aslam  3 , Ayesha Akram  1 , Adina Arshad  1 , Muhammad Irfan  1
Affiliations
Meta-Analysis

Association of ESR1 Xba1 (rs9340799) With Male Infertility: A Systematic Review and Meta-Analysis

Hania Qamar et al. Am J Mens Health. 2025 Jan-Feb.

Abstract

Variations in the estrogen receptor genes, particularly the Xba1 (rs9340799) SNP in the ESR1 gene, may influence the effects of estrogen on male fertility. Results from previous studies on this SNP for male infertility have been inconclusive. This review aimed to determine the association of ESR1 Xba1 (rs9340799) with male infertility. Relevant case-control studies published in English were searched from Google Scholar, Embase, Scopus, Web of Science, Cochrane Library, and PubMed using keywords of ESR, polymorphism, and male infertility. Studies on animals, reviews, and abstracts were excluded. Pooled odds ratios (ORs) were calculated for four genetic models, with heterogeneity assessed by I2. A fixed or random effect model was applied based on I2, and trial sequential analysis (TSA) was conducted with 5% significance for type I error and 95% power. ESR1 expression levels were examined in testes, hypothalamus, prostate, and pituitary using GTEx Analysis. Nine studies (four Asian, four Caucasian, one African) met the criteria. The G allele was protective against infertility overall (OR: 0.80; 95% confidence interval [CI] = [0.70, 0.92]) and in Caucasian men (OR: 0.71; 95% CI = [0.54, 0.92]). Lower infertility risk was observed in Asian (AA vs. GG OR: 0.65; 95% CI = [0.43, 0.98]) and Caucasian men (OR: 0.49; 95% CI = [0.28, 0.83]). TSA indicated no further studies are likely to change these results. No significant change in expression of ESR1 was observed due to this SNP. The present meta-analysis suggests that the SNP Xba1 (rs9340799) in ESR1 is protective against male infertility, with current data sufficient to confirm these findings.

Keywords: estrogen receptor alpha; infertility; oligospermia; polymorphism.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Flowchart Showing the Selected Studies
Figure 2.
Figure 2.
Funnel Plot Assessing Publication Bias for the Association Between ESR1 Xbal Polymorphism and Male Infertility Note. Each dot represents an individual study included in the meta-analysis, plotted according to its effect size (log odds ratio) on the x-axis and standard error on the y-axis.
Figure 3.
Figure 3.
Trial Sequential Analysis for A to G
Figure 4.
Figure 4.
Graphs Showing Influence of the Polymorphisms (rs9340799) on the Expression of ESR1 Gene in the Testicular, Hypothalamus, Pituitary, and Prostate Tissue
See this image and copyright information in PMC

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