Effect of folate deficiency on promoter methylation and gene expression of Esr1, Cav1, and Elavl1, and its influence on spermatogenesis

// Hong-Fang Yuan 1,* , Kai Zhao 1,2,* , Yu Zang 3 , Chun-Yan Liu 1 , Zhi-Yong Hu 1 , Jia-Jing Wei 1 , Ting Zhou 1 , Ying Li 1 and Hui-Ping Zhang 1,2 1 Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 2 Center of Human Reproduction, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 3 Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China * Co-first authors Correspondence to: Hui-Ping Zhang, email: // Keywords : folate deficiency; spermatogenesis; methylation; male infertility; gene expression; Pathology Section Received : December 21, 2016 Accepted : February 08, 2017 Published : February 25, 2017 Abstract This study aims to investigate the effect of folate deficiency on the male reproductive function and the underlying mechanism. A total of 269 screened participants from 421 recruitments were enrolled in this study. An animal model of folate deficiency was constructed. Folate concentration was measured in the ejaculate, and its association with semen parameters was then determined. The expression and promoter methylation status of ESR1 , CAV1 , and ELAVL1 were also evaluated. Results showed that seminal plasma folate level was significantly lower among subjects with azoospermia than those with normozoospermia. Low folate level was significantly correlated with low sperm concentration in men with normozoospermia. Folate deficiency significantly reduced the expression of ESR1 , CAV1 , and ELAVL1 , which are critical to spermatogenesis. However, low folate levels did not increase the methylation levels of the promoter regions of ESR1 , CAV1 , and ELAVL1 in human sperm DNA. Thus, folate deficiency impairs spermatogenesis may partly due to inhibiting the expression of these genes. Thus future research should determine the significance of sufficient folate status in male fertilization and subsequent pregnancy outcomes.