Premium
Neonatal hypothyroidism affects testicular glucose homeostasis through increased oxidative stress in prepubertal mice: effects on GLUT 3, GLUT 8 and Cx43
Author(s) -
Sarkar D.,
Singh S. K.
Publication year - 2017
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12363
Subject(s) - glut3 , medicine , endocrinology , glucose transporter , oxidative stress , homeostasis , glucose homeostasis , biology , chemistry , glut1 , insulin resistance , insulin
Summary Thyroid hormones ( TH s) play an important role in maintaining the link between metabolism and reproduction and the altered TH s status is associated with induction of oxidative stress in various organs like brain, heart, liver and testis. Further, reactive oxygen species play a pivotal role in regulation of glucose homeostasis in several organs, and glucose utilization by Leydig cells is essential for testosterone biosynthesis and thus is largely dependent on glucose transporter 8 ( GLUT 8). Glucose uptake by Sertoli cells is mediated through glucose transporter 3 ( GLUT 3) under the influence of TH s to meet energy requirement of developing germ cells. TH s also modulate level of gap junctional protein such as connexin 43 (Cx43), a potential regulator of cell proliferation and apoptosis in the seminiferous epithelium. Although the role of transient neonatal hypothyroidism in adult testis in terms of testosterone production is well documented, the effect of TH s deficiency in early developmental period and its role in testicular glucose homeostasis and oxidative stress with reference to Cx43 in immature mice remain unknown. Therefore, the present study was conducted to evaluate the effect of neonatal hypothyroidism on testicular glucose homeostasis and oxidative stress at postnatal days ( PND ) 21 and 28 in relation to GLUT 3, GLUT 8 and Cx43. Hypothyroidism induced by 6‐propyl‐2‐thiouracil ( PTU ) markedly decreased testicular glucose level with considerable reduction in expression level of GLUT 3 and GLUT 8. Likewise, lactate dehydrogenase ( LDH ) activity and intratesticular concentration of lactate were also decreased in hypothyroid mice. There was also a rise in germ cell apoptosis with increased expression of caspase‐3 in PTU ‐treated mice. Further, neonatal hypothyroidism affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen ( PCNA ) and Cx43. In conclusion, our results suggest that neonatal hypothyroidism alters testicular glucose homeostasis via increased oxidative stress in prepubertal mice, thereby affecting germ cell survival and proliferation.