Female infertility in mice deficient in midkine and pleiotrophin, which form a distinct family of growth factors.
Midkine and pleiotrophin form a family of growth factors. Mice deficient in one of the genes show few abnormalities on reproduction and development. To understand their roles in these processes, we produced mice deficient in both genes; the double deficient mice were born in only one third the number expected by Mendelian segregation and 4 weeks after birth weighed about half as much as wild-type mice. Most of the female double deficient mice were infertile. In these mice, the numbers of mature follicles and of ova at ovulation were reduced compared to numbers in wild-type mice. Both midkine and pleiotrophin were expressed in the follicular epithelium and granulosa cells of the ovary. The expression of these factors in the uterus was dramatically altered during the estrous cycle. The diestrus and proestrus periods were long and the estrus period was short in the double deficient mice, indicating the role of the factors in the estrous cycle. Furthermore, vaginal abnormality was found in about half of the double deficient mice. These abnormalities in combination resulted in female infertility. Therefore, midkine and pleiotrophin, together with their signaling receptors, play important roles in the female reproductive system.
Muramatsu
Hisako
H
Department of Biochemistry, Center for Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Zou
Peng
P
Kurosawa
Nobuyuki
N
Ichihara-Tanaka
Keiko
K
Maruyama
Kiyoko
K
Inoh
Kazuhiko
K
Sakai
Takayuki
T
Chen
Lan
L
Sato
Masahiro
M
Muramatsu
Takashi
T
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003433:Crosses, Genetic; D016207:Cytokines / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism; D007247:Infertility, Female / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D000078792:Midkine; D006080:Ovarian Follicle / Q000378:metabolism; D014621:Vagina / Q000002:abnormalities
D002352:Carrier Proteins; D016207:Cytokines; C066845:pleiotrophin; D000078792:Midkine