help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

Molecular Endocrinology, doi:10.1210/me.2008-0142
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nagaraja, A. K.
Right arrow Articles by Matzuk, M. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nagaraja, A. K.
Right arrow Articles by Matzuk, M. M.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*ESTRADIOL
*MENOTROPINS
Medline Plus Health Information
*Infertility
Molecular Endocrinology 22 (10): 2336-2352
Copyright © 2008 by The Endocrine Society

Deletion of Dicer in Somatic Cells of the Female Reproductive Tract Causes Sterility

Ankur K. Nagaraja1, Claudia Andreu-Vieyra1, Heather L. Franco, Lang Ma, Ruihong Chen, Derek Y. Han, Huifeng Zhu, Julio E. Agno, Preethi H. Gunaratne, Francesco J. DeMayo and Martin M. Matzuk

Departments of Pathology (A.K.N., C.A.-V., L.M., R.C., D.Y.H., J.E.A., P.H.G., M.M.M.), Molecular and Human Genetics (A.K.N., M.M.M.), and Molecular and Cellular Biology (H.L.F., F.J.D., M.M.M.), Human Genome Sequencing Center (P.H.G.), and Program in Developmental Biology (F.J.D., M.M.M.), Baylor College of Medicine, Houston, Texas 77030; and Departments of Physics (H.Z.) and Biology and Biochemistry (P.H.G.), University of Houston, Houston, Texas 77004

Address all correspondence and requests for reprints to: Martin M. Matzuk, M.D., Ph.D., Stuart A. Wallace Chair and Professor, Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Room S217, Houston, Texas 77030. E-mail: mmatzuk{at}bcm.edu.

Dicer is an evolutionarily conserved ribonuclease III that is necessary for microRNA (miRNA) processing and the synthesis of small interfering RNAs from long double-stranded RNA. Although it has been shown that Dicer plays important roles in the mammalian germline and early embryogenesis, the functions of Dicer-dependent pathways in the somatic cells of the female reproductive tract are unknown. Using a transgenic line in which Cre recombinase is driven by the anti-Müllerian hormone receptor type 2 promoter, we conditionally inactivated Dicer1 in the mesenchyme of the developing Müllerian ducts and postnatally in ovarian granulosa cells and mesenchyme-derived cells of the oviducts and uterus. Deletion of Dicer in these cell types results in female sterility and multiple reproductive defects including decreased ovulation rates, compromised oocyte and embryo integrity, prominent bilateral paratubal (oviductal) cysts, and shorter uterine horns. The paratubal cysts act as a reservoir for spermatozoa and oocytes and prevent embryos from transiting the oviductal isthmus and passing the uterotubal junction to enter the uterus for implantation. Deep sequencing of small RNAs in oviduct revealed down-regulation of specific miRNAs in Dicer conditional knockout females compared with wild type. The majority of these differentially expressed miRNAs are predicted to regulate genes important for Müllerian duct differentiation and mesenchyme-derived structures, and several of these putative target genes were significantly up-regulated upon conditional deletion of Dicer1. Thus, our findings reveal diverse and critical roles for Dicer and its miRNA products in the development and function of the female reproductive tract.




This article has been cited by other articles:


Home page
Endocr. Rev.Home page
M. A. Edson, A. K. Nagaraja, and M. M. Matzuk
The Mammalian Ovary from Genesis to Revelation
Endocr. Rev., October 1, 2009; 30(6): 624 - 712.
[Abstract] [Full Text] [PDF]


Home page
Hum Reprod UpdateHome page
E. M. C. Ohlsson Teague, C. G. Print, and M. L. Hull
The role of microRNAs in endometriosis and associated reproductive conditions
Hum. Reprod. Update, September 22, 2009; (2009) dmp034v1.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
S. C. Bannister, M. L.V. Tizard, T. J. Doran, A. H. Sinclair, and C. A. Smith
Sexually Dimorphic MicroRNA Expression During Chicken Embryonic Gonadal Development
Biol Reprod, July 1, 2009; 81(1): 165 - 176.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2008 by The Endocrine Society