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Updated: Aug 6, 2026
Collection of Human Follicular Fluid, Follicle Somatic Cells, and Immature Oocytes from Individuals Undergoing In Vitro Fertilization
Published on: October 24, 2025
Association between heavy metals, essential trace elements in follicular fluid and diminished ovarian reserve: a
Xin-Chen Huang1, Ming-Li Sun2, Yi-Qin Chen3
1School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.
Objective:
To investigate the distribution of heavy metals and essential trace elements in follicular fluid (FF) and their association with diminished ovarian reserve (DOR) using a clinical epidemiological approach.
Methods:
A hospital-based case-control study was conducted. Following propensity score matching (PSM) to control for demographic confounders (age and BMI), baseline clinical data and FF samples were analyzed. Inductively coupled plasma mass spectrometry was used to quantify metal elements in FF. Associations were evaluated using Spearman correlation analysis, weighted quantile sum (WQS) regression, Bayesian kernel machine regression (BKMR), and least absolute shrinkage and selection operator (LASSO) regression.
Results:
FF concentrations of arsenic (As), strontium (Sr), and calcium (Ca) were significantly higher in the DOR group than in the control group (P (As) = 0.001, P (Sr) < 0.001, P (Ca) = 0.002). Spearman correlation analysis revealed significant positive correlations between As and selenium, Sr, and vanadium (V). Logistic regression demonstrated that As (odds ratio [OR] = 4.727, 95% confidence interval [CI]: 2.456-9.611) and Sr (OR = 1.984, 95% CI: 1.350-2.985) were associated with higher odds of DOR, whereas copper (OR = 0.552, 95% CI: 0.359-0.831), V (OR = 0.366, 95% CI: 0.183-0.716), and zinc (Zn) (OR = 0.497, 95% CI: 0.308-0.789) were associated with lower odds of DOR. The WQS regression identified Sr, As, and Ca as the primary contributors to the mixture (weights: 0.398, 0.302, and 0.277, respectively). The BKMR model suggested a positive but relatively weak overall mixture effect of metal exposure on the likelihood of DOR. In the advanced mixture model, As, Ca, and iron (Fe) were positively associated with DOR, whereas Zn was negatively associated with DOR, with V and Sr no longer retained as independent factors.
Conclusion:
Heavy metals and essential trace elements in FF exhibit joint mixture effects in the pathogenesis of DOR. While Sr serves as a surrogate marker for cumulative exposure, As, Ca, and Fe are independently and positively associated with the likelihood of DOR, whereas Zn exhibits a protective association. Maintaining local trace element homeostasis may be critical for preserving ovarian reserve.
