Insulin receptor and IGF1R are not required for oocyte growth, differentiation, and maturation in mice.
In mammals, insulin and insulin-like growth factors (IGFs: IGF1 and IGF2) act through 2 structurally related receptors, the insulin receptor (INSR) and the type 1 IGF receptor (IGF1R), both of which are expressed in developing oocytes. IGF1 plays an important role in female reproduction, and female Igf1 knockout mice fail to ovulate and are infertile. On the other hand, little is known about the in vivo role of the insulin signaling pathway in oocytes during follicular development, although exposure to insulin or IGF1 in vitro improves oocyte maturation. To further address the significance of insulin/IGF signaling, we used conditional mutant mice and ablated the function of the genes encoding INSR, IGF1R, or both receptors specifically in developing mouse oocytes. Our genetic evidence showed unexpectedly that the female reproductive functions are not affected when Insr, Igf1r or both Insr;Igf1r are ablated in oocytes, as the female mice are fertile and exhibit normal estrous cyclicity, oocyte development and maturation, parturition frequency, and litter size. In view of these novel observations indicating that the insulin/IGF signaling is not essential in oocytes, the IGF1-dependent female fertility is re-evaluated and discussed.
Pitetti
J L
JL
Department of Genetic Medicine and Development, University of Geneva Medical School, University of Geneva, CH-1211 Geneva 4, Switzerland.
Torre
D
D
Conne
B
B
Papaioannou
M D
MD
Cederroth
C R
CR
Xuan
S
S
Kahn
R
R
Parada
L F
LF
Vassalli
J D
JD
Efstratiadis
A
A
Nef
S
S
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology*; D009866:Oogenesis / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin