Premature ovarian aging in mice deficient for Gpr3.
After becoming competent for resuming meiosis, fully developed mammalian oocytes are maintained arrested in prophase I until ovulation is triggered by the luteotropin surge. Meiotic pause has been shown to depend critically on maintenance of cAMP level in the oocyte and was recently attributed to the constitutive Gs (the heterotrimeric GTP-binding protein that activates adenylyl cyclase) signaling activity of the G protein-coupled receptor GPR3. Here we show that mice deficient for Gpr3 are unexpectedly fertile but display progressive reduction in litter size despite stable age-independent alteration of meiotic pause. Detailed analysis of the phenotype confirms premature resumption of meiosis, in vivo, in about one-third of antral follicles from Gpr3-/- females, independently of their age. In contrast, in aging mice, absence of GPR3 leads to severe reduction of fertility, which manifests by production of an increasing number of nondeveloping early embryos upon spontaneous ovulation and massive amounts of fragmented oocytes after superovulation. Severe worsening of the phenotype in older animals points to an additional role of GPR3 related to protection (or rescue) of oocytes from aging. Gpr3-defective mice may constitute a relevant model of premature ovarian failure due to early oocyte aging.
Ledent
Catherine
C
Institut de Recherches en Biologie Humaine et Moléculaire, University of Brussels, Campus Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium. cledent@ulb.ac.be
Demeestere
Isabelle
I
Blum
David
D
Petermans
Julien
J
Hämäläinen
Tuula
T
Smits
Guillaume
G
Vassart
Gilbert
G
D000818:Animals; D047108:Embryonic Development; D004971:Estrus / Q000502:physiology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005822:Genetic Vectors; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D010053:Ovary / Q000254:growth & development* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013480:Superovulation / Q000235:genetics*
C494613:GPR3 protein, mouse; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D005640:Follicle Stimulating Hormone