TY - JOUR
T1 - Leptin monotherapy rescues spermatogenesis in male akita type 1 diabetic mice
AU - Schoeller, Erica L.
AU - Chi, Maggie
AU - Drury, Andrea
AU - Bertschinger, Ashley
AU - Esakky, Prabagaran
AU - Moley, Kelle H.
PY - 2014/8
Y1 - 2014/8
N2 - Type 1 diabetes is associated with subfertility in humans. The current treatment for type 1 diabetes, insulin monotherapy, is suboptimal to fully stabilize glycemia, potentially leading to this subfer-tility. Recent work has demonstrated that treatment with the energy-regulating hormone leptin, alone or in combination with insulin, can more effectively control glycemia in mouse models of type 1 diabetes. Here, we sought to determine whether the fertility defects in a type 1 diabetic mouse model, the Akita mouse, can be rescued with leptin monotherapy in the absence of any exogenous insulin. Akita homozygous mice treated with leptin alone had a larger total body size, testes, and seminal vesicles than their untreated siblings. Leptin treatment prevented testicular degeneration and rescued sperm motility to wild-type levels. Furthermore, sperm obtained from leptin-treated mice could successfully fertilize ooctyes in vitro. Despite completely rescuing spermatogenesis, the critical reproductive hormones LH and testosterone were only modestly higher than in untreated mice, indicatingthat a minimum threshold of these hormones must be metto maintain spermatogenesis. Cumulatively, these findings implicate the importance of leptin in maintaining fertility and support the use of leptin therapy in the treatment of type 1 diabetes.
AB - Type 1 diabetes is associated with subfertility in humans. The current treatment for type 1 diabetes, insulin monotherapy, is suboptimal to fully stabilize glycemia, potentially leading to this subfer-tility. Recent work has demonstrated that treatment with the energy-regulating hormone leptin, alone or in combination with insulin, can more effectively control glycemia in mouse models of type 1 diabetes. Here, we sought to determine whether the fertility defects in a type 1 diabetic mouse model, the Akita mouse, can be rescued with leptin monotherapy in the absence of any exogenous insulin. Akita homozygous mice treated with leptin alone had a larger total body size, testes, and seminal vesicles than their untreated siblings. Leptin treatment prevented testicular degeneration and rescued sperm motility to wild-type levels. Furthermore, sperm obtained from leptin-treated mice could successfully fertilize ooctyes in vitro. Despite completely rescuing spermatogenesis, the critical reproductive hormones LH and testosterone were only modestly higher than in untreated mice, indicatingthat a minimum threshold of these hormones must be metto maintain spermatogenesis. Cumulatively, these findings implicate the importance of leptin in maintaining fertility and support the use of leptin therapy in the treatment of type 1 diabetes.
UR - http://www.scopus.com/inward/record.url?scp=84904962599&partnerID=8YFLogxK
U2 - 10.1210/en.2014-1119
DO - 10.1210/en.2014-1119
M3 - Review article
C2 - 24840347
AN - SCOPUS:84904962599
VL - 155
SP - 2781
EP - 2786
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 8
ER -