In utero methoxychlor exposure increases rat fetal Leydig cell number but inhibits its function.
The objective of the present study is to determine whether in utero exposure to methoxychlor (MXC) affects rat fetal Leydig cell number, cell size, or functions. Pregnant Sprague Dawley dams were gavaged with corn oil (control, 0mg/kg/day MXC) or MXC at doses of 10, 50, or 100mg/kg/day from gestational day (GD) 12 to 21. The results show that MXC increased fetal Leydig cell numbers dose-dependently from 95±8×103cells/testis (control, mean±SEM) to 101±6, 148±22, and 168±21×103cells/testis, at the doses of 10, 50, and 100mg/kg, respectively. The increase of Leydig cell number by MXC was contributed by the increase of single cell population of Leydig cells, which increased from 21±2% of the control to 31±4%, 39±3%, or 40±4% at the doses of 10, 50 or 100mg/kg, respectively. Quantitative PCR results show that MXC increased Lhcgr expression at dose of 10mg/kg and Scarb1 and Cyp11a1 mRNA levels at doses of 50 and 100mg/kg. Immunohistochemical staining demonstrated the increase of CYP11A1 protein level from the dose of 10mg/kg. However, at the highest dose (100mg/kg) MXC reduced the testicular testosterone level and MXC (1μM) in vitro treatment also inhibited androgen production from isolated fetal Leydig cells. In conclusion, our findings indicate that at low dose MXC may increase fetal Leydig cell numbers and the expressions of some steroidogenic enzymes, but at high dose it reduces the testicular testosterone level leading to reproductive tract malformations in the male offspring.
Department of Anesthesiology, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Shiwen
S
Liu
Center for Scientific Research, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Chao
C
Li
Department of Anesthesiology, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Yiyan
Y
Wang
Center for Scientific Research, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Tingting
T
Hong
Department of Anesthesiology, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Tiantian
T
Song
Center for Scientific Research, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Linxi
L
Li
Department of Pediatrics, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Leping
L
Ye
Department of Anesthesiology, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Qingquan
Q
Lian
Department of Anesthesiology, The 2nd Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: r_ge@yahoo.com.
Ren-Shan
RS
Ge
D000728:Androgens / Q000378:metabolism; D000818:Animals; D002452:Cell Count; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008731:Methoxychlor / Q000633:toxicity*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D012333:RNA, Messenger; D013739:Testosterone; D002786:Cholesterol Side-Chain Cleavage Enzyme; D008731:Methoxychlor
Cell number; Fetal Leydig cells; Methoxychlor; Steroidogenesis