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Effect of maternal folic acid supplementation on prostatitis risk in the rat offspring

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Folic acid (FA) intake has increased to high levels in many countries for the prevention of neural tube defects. However, the impact of excess FA intake, particularly before and during pregnancy, requires further investigation. Our aim was to investigate the effect of maternal folic acid supplementation on prostatitis risk in the rat offspring.


Female SD rats were administrated with different doses of FA by oral gavage from 2 weeks prior to mating to GD14: 0 mg/kg (distilled water), 0.2 mg/kg FA and 2.0 mg/kg FA respectively. The male rat offspring from each maternal FA group were castrated on PND56 and injected different doses of 17β-estradiol (E2) subcutaneously for 30 days to induce prostatitis: 0 mg/kg (corn oil) and 1.25 mg/kg E2 respectively. At necropsy, the prostates were collected for histopathological analysis. Fasting blood was collected for the determination of serum E2, T, DHT, and folic acid levels. The expression of TNF-α, COX-2, and ER-α was determined by immunohistochemistry.


High-dose (2.0 mg/kg) maternal folic acid supplementation significantly increased the proportion of prostatitis in FA(2.0) + E2(1.25) group (87.5%) compared with FA(0) + E2(1.25) group (25%). The inflammation was focal and severe, and large amounts of inflammatory cells appeared in different regions of the prostate in FA(2.0) + E2(1.25) group. The serum T, DHT, and FA levels in FA(2.0) + E2(1.25) group were significantly higher than those in FA(0) + E2(1.25) group. The expression of TNF-α, COX-2, and ER-α in three 1.25 mg/kg E2 groups presented positive, and the number and distribution of positive cells increased as FA dosage increased.


Our findings suggest that high-dose (2.0 mg/kg) maternal folic acid supplementation significantly increases the proportion of prostatitis and the prostatic inflammation is more obvious and severe in the rat offspring.

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This study was funded by Shanghai Research and Development Platform (Grant Number 17DZ2293600) and Shanghai Experimental Animal Scientific and Technological Innovative Action Plan (Grant Number 17140900801).

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Correspondence to Li Zhou or Zu-yue Sun.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Informed consent was obtained from all individual participants included in the study.

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Zhu, J., Jia, Yl., Luo, Yw. et al. Effect of maternal folic acid supplementation on prostatitis risk in the rat offspring. Int Urol Nephrol 50, 1963–1973 (2018).

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