TY - JOUR
T1 - Disruption of NHE8 expression impairs Leydig cell function in the testes
AU - Xu, Hua
AU - Chen, Huacong
AU - Li, Jing
AU - Zhao, Yang
AU - Ghishan, Fayez K.
N1 - Publisher Copyright:
© 2015 the American Physiological Society.
PY - 2015
Y1 - 2015
N2 - Multiple sodium/hydrogen exchanger (NHE) isoforms are expressed in the testes, and they play various roles in cell volume regulation, intracellular pH regulation, and fluid absorption. NHE8, the most recently characterized NHE family member, is detected in the Leydig cells in humans and mice in great abundance by immunohistochemistry in the current study. Male mice lacking NHE8 expression were infertile. Despite having intact male reproductive organs, male NHE8-/- mice have smaller testes and lacked spermatozoon in the seminiferous tubules and the epididymis. At the age of 39 wk, few spermogonia were seen in the testis in NHE8-/- mice. Although male NHE8-/- mice have normal serum levels of luteinizing hormone and follicle-stimulating hormone, serum testosterone level was significantly reduced. These mice have decreased expression of luteinizing hormone receptor in the testes. In NHE8 small-interfering RNA-transfected mouse Leydig cells (MLTC-1), silencing of NHE8 decreased the expression of luteinizing hormone receptor by ~70%. Moreover, loss of NHE8 function in Leydig cells resulted in disorganized luteinizing hormone receptor membrane distribution. Therefore, male infertility in NHE8-/- mice is at least partially due to the disruption of luteinizing hormone receptor distribution and consequent low testosterone production, which leads to Sertoli cell dysfunction. Our work identified a novel role of NHE8 in male fertility through its effect on modifying luteinizing hormone receptor function.
AB - Multiple sodium/hydrogen exchanger (NHE) isoforms are expressed in the testes, and they play various roles in cell volume regulation, intracellular pH regulation, and fluid absorption. NHE8, the most recently characterized NHE family member, is detected in the Leydig cells in humans and mice in great abundance by immunohistochemistry in the current study. Male mice lacking NHE8 expression were infertile. Despite having intact male reproductive organs, male NHE8-/- mice have smaller testes and lacked spermatozoon in the seminiferous tubules and the epididymis. At the age of 39 wk, few spermogonia were seen in the testis in NHE8-/- mice. Although male NHE8-/- mice have normal serum levels of luteinizing hormone and follicle-stimulating hormone, serum testosterone level was significantly reduced. These mice have decreased expression of luteinizing hormone receptor in the testes. In NHE8 small-interfering RNA-transfected mouse Leydig cells (MLTC-1), silencing of NHE8 decreased the expression of luteinizing hormone receptor by ~70%. Moreover, loss of NHE8 function in Leydig cells resulted in disorganized luteinizing hormone receptor membrane distribution. Therefore, male infertility in NHE8-/- mice is at least partially due to the disruption of luteinizing hormone receptor distribution and consequent low testosterone production, which leads to Sertoli cell dysfunction. Our work identified a novel role of NHE8 in male fertility through its effect on modifying luteinizing hormone receptor function.
KW - Luteinizing hormone receptor
KW - Sodium/proton exchanger 8
KW - Testis
KW - Testosterone
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U2 - 10.1152/ajpcell.00289.2014
DO - 10.1152/ajpcell.00289.2014
M3 - Article
C2 - 25472965
AN - SCOPUS:84922879138
SN - 0363-6143
VL - 308
SP - C330-C338
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 4
ER -