4-Nitrophenol induces Leydig cells hyperplasia, which may contribute to the differential modulation of the androgen receptor and estrogen receptor-α and -β expression in male rat testes.
4-Nitrophenol (PNP) is generally regarded as an environmental endocrine disruptor capable of estrogenic and anti-androgenic activities. To investigate PNP-induced reproductive effects, immature male rats were injected subcutaneously with PNP (0.1, 1, 10mg/kg body weight or vehicle) daily for 4 weeks. We assessed reproductive tract alterations, sex hormone balance in the serum and estrogen receptor (ER)-α, -β and androgen receptor (AR) expression in testes. Although no significant difference was observed in body weight or testes weights of PNP-treated rats compared with the controls, the serum concentrations of testosterone in the 10mg/kg PNP-treated group were significantly elevated. This effect was accompanied by Leydig cells hyperplasia in the testes. Conversely, there was a significant decrease in estradiol concentration and aromatase expression in the testes of the 10mg/kg PNP-treated group. Furthermore, we observed a significant increase in ERα expression in the testes of the 10mg/kg PNP-treated group compared with the control group. Conversely, ERβ expression displayed a significant reduction. Moreover, AR expression was significantly increased in the 10mg/kg PNP-treated group compared with the control group. The existence of AR, ER-α and -β in the testes suggests that estradiol and testosterone directly affect germ cells and that differential modulation of AR, ER-α and -β in the testis may be involved in the direct effects of PNP or either the indirect effects of PNP-induced disruption of the estradiol-to-testosterone balance or the Leydig cells hyperplasia. Thus, the measurement of many endpoints is necessary for good risk assessment.
College of Animal Science and Technology, Nanjing Agricultural University, No. 1 Weigang, Nanjing 210095, PR China.
Yonghui
Y
Zhang
Yuanguo
Y
Piao
Yansen
Y
Li
Meiyan
M
Song
Pingli
P
Tang
Chunmei
C
Li
D000726:Androgen Antagonists / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D012739:Gonadal Steroid Hormones / Q000097:blood; D006965:Hyperplasia; D007150:Immunohistochemistry; D007985:Leydig Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009596:Nitrophenols / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000187:drug effects* / Q000473:pathology
D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012739:Gonadal Steroid Hormones; D009596:Nitrophenols; D011944:Receptors, Androgen; D001141:Aromatase; C024836:4-nitrophenol
4-Nitrophenol; 4-nitrophenol; AR; Androgen receptor; BSA; DEP; EEDs; ER; Estrogen receptor; FSH; HE; Hormonal balance; LH; Leydig cells; PBS; PNP; SD; Sprague-Dawley; androgen receptor; bovine serum albumin.; diesel exhaust particles; environmental endocrine disruptors; estrogen receptor; follicle-stimulating hormone; hematoxylin and eosin; luteinizing hormone; phosphate-buffered saline