Mechanisms of male reproductive tract development regulated by Cxxc5 in the female reproductive tract primordium

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07243
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Harada Masayo 東京医科歯科大学, 大学院医歯学総合研究科, 講師(キャリアアップ) (80555756)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 中腎管 / 中腎傍管 / 精管 / 精嚢 / Cxxc5

Outline of Final Research Achievements

The Wolffian duct (future epididymis, vas deference, seminal vesicle, and ampullary gland) and Mullerian duct (future oviduct, uterus, and vagina) form similarly in males and females during embryonic development. In male embryo, the Mullerian duct degenerates and the Wolffian duct differentiates. Whereas, in female embryo, the Wolffian duct degenerates and the Mullerian duct differentiates. We revealed that the loss of Cxxc5 in the Mullerian duct induced distal Mullerian duct elongation defects and the Mullerian ductal tip persistence at abnormally rostral position leading to morphological defects of distal reproductive tract organs such as distal vas deference, seminal vesicle, and ampullary gland in male mice. The sperm were ejaculated through a detour in seminal vesicle, and thus might lost their fertility in those infertile mutant mice.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

過去の研究では、雄性不妊の原因について雄性生殖管にのみ着目しているが、本研究は、雄性不妊が雌性生殖管（中腎傍管）の発生異常によりもたらされるという新機構を提唱するものである。中腎傍管特異的Cxxc5欠損雄マウスが示す中腎傍管の残存は、ヒトで、男性不妊をもたらす中腎傍管嚢胞の症例と類似している。しかしながら、なぜ男性で中腎傍管が残存するのか、女性生殖管原基である中腎傍管の残存がなぜ男性不妊をもたらすのか、その機序は分かっていない。よって、本研究が、ヒト男性不妊症である中腎傍管嚢胞の発症機序解明に貢献できる可能性がある。