Cholesterol homeostasis is strictly maintained to prevent abnormal biological processes that arise from excessive accumulation of cholesterol in tissues. Although dyslipidemia causes reproductive dysfunction and endocrine disruption in male rats, regulatory factors and mechanisms have not been clearly demonstrated. Therefore, the present study investigated the histology of male reproductive organs and the expression of prostatic acid phosphatase (also known as Acpp) that is secreted by cuboidal epithelium of the prostate gland in response to a normal diet and a high-cholesterol diet. The high cholesterol diet increased total cholesterol and low density lipoprotein (LDL) levels and decreased high density lipoprotein (HDL) levels. Histological analyses showed considerable alterations in the prostate indicating excessive papillary projections within the acinar lumen in response to the high cholesterol diet. In addition, Acpp expression was decreased in the penis of rats fed the high cholesterol diet and it was predominantly localized in the urethral epithelium and penile follicle that is precursor of penile spines. Moreover, Acpp was reduced slightly in the testes, but differential expression of Acpp in the prostate in response to dietary cholesterol was not detected. Furthermore, target microRNAs (miRs) of Acpp such as miR-192 and miR-215 regulated Acpp gene expression at the post-transcriptional levels by binding to specific sites within its 3'-UTR. These results indicate that Acpp plays an important role in growth and development of the penis of rats, and its expression is modulated at epigenomic levels via specific miRs. (C) 2014 Elsevier Inc. All rights reserved.