2006 Fiscal Year Final Research Report Summary
Analysis of the mechanism causing female infertility in mice deficient midkine and pleiotrophin.
| Project/Area Number |
17590245
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
MURAMATSU Hisako Nagoya University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (50182134)
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| Co-Investigator(Kenkyū-buntansha) |
KADOMATSU Kenji Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (80204519)
SATO Masahiro Kagoshima University, Center For Frontier Science, Professor, フロンティアサイエンス研究推進センター, 教授 (30287099)
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| Project Period (FY) |
2005 – 2006
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| Keywords | midkine / pleiotrophin / gene-deficient mouse / female fertility |
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| Research Abstract |
Midkine and pleiotrophin form a family of growth factors, and display diverse physiological activities, such as promotion of growth, survival and migration of various cells. Mice deficient in one of the genes show few abnormalities upon reproduction and development. To understand their roles in these processes, we produced mice deficient in both genes; the double deficient (DKO) mice were born in only 1/3 the number expected by Mendelian segregation, and 4 weeks after birth weighed about half as much as wild-type (WT) 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 WT 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 DKO mice, indicating the role of the factors in the estrous cycle. Furthermore, vaginal abnormality was found in about half of DKO mice. All DKO mice with an abnormal vagina were sterile, without any sign of a plug. Furthermore, we found that DKO mice had a thin vaginal epithelium as compared to age-matched WT mice. These abnormalities in combination resulted in female infertility. Therefore, midkine and pleiotrophin as well as their signaling receptors play important roles in the female reproductive system.
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