title: microRNA 376a regulates follicle assembly by targeting Pcna in fetal and neonatal mouse ovaries.
abstract: In mammals, the primordial follicle pool, providing all oocytes available to a female throughout her reproductive life, is established perinatally. Dysregulation of primordial follicle assembly results in female reproductive diseases, such as premature ovarian insufficiency and infertility. Female mice lacking Dicer1 (Dicer), a gene required for biogenesis of microRNAs, show abnormal morphology of follicles and infertility. However, the contribution of individual microRNAs to primordial follicle assembly remains largely unknown. Here, we report that microRNA 376a (miR-376a) regulates primordial follicle assembly by modulating the expression of proliferating cell nuclear antigen (Pcna), a gene we previously reported to regulate primordial follicle assembly by regulating oocyte apoptosis in mouse ovaries. miR-376a was shown to be negatively correlated with Pcna mRNA expression in fetal and neonatal mouse ovaries and to directly bind to Pcna mRNA 3' untranslated region. Cultured 18.5 days postcoitum mouse ovaries transfected with miR-376a exhibited decreased Pcna expression both in protein and mRNA levels. Moreover, miR-376a overexpression significantly increased primordial follicles and reduced apoptosis of oocytes, which was very similar to those in ovaries co-transfected with miR-376a and siRNAs targeting Pcna. Taken together, our results demonstrate that miR-376a regulates primordial follicle assembly by modulating the expression of Pcna. To our knowledge, this is the first microRNA-target mRNA pair that has been reported to regulate mammalian primordial follicle assembly and further our understanding of the regulation of primordial follicle assembly.
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Hua
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China.
authors.forename: Tieliang
authors.initials: T
authors.lastname: Ma
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, ChinaHefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Cooke
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China.
authors.forename: Qiaomei
authors.initials: Q
authors.lastname: Hao
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of ChinaLaboratory of Germ Cell BiologyKey Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University, Qingdao, Shandong, ChinaMRC Human Genetics UnitInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UKDepartment of Obstetrics and GynecologyReproductive Medical Centre, Peking University Third Hospital, Beijing, China qshi@ustc.edu.cn.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Shi
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001665:Binding Sites; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005865:Gestational Age; D057809:HEK293 Cells; D006801:Humans; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D006080:Ovarian Follicle / Q000196:embryology / Q000378:metabolism*; D010053:Ovary / Q000196:embryology / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C000594936:MIRN376 microRNA, mouse; D035683:MicroRNAs; D018809:Proliferating Cell Nuclear Antigen