title: Robo1/2 regulate follicle atresia through manipulating granulosa cell apoptosis in mice.
abstract: Secreted Slit proteins and their Roundabout (Robo) receptors act as a repulsive cue to prevent axons from migrating to inappropriate locations during the development of the nervous system. Slit/Robo has also been implicated in reproductive system development, but the molecular mechanism of the Slit/Robo pathway in the reproductive system remains poorly understood. Using a transgenic mouse model, we investigated the function of the Slit/Robo pathway on ovarian follicle development and atresia. We first demonstrated that more offspring were born to mice with a partial knockout of the Robo1/2 genes in mice. We next showed that Robo1 and Robo2 are strongly expressed in ovarian granulosa cells. Apoptosis in granulosa cells was reduced when Robo1/2 were partially knocked out, and this observation was further verified by in vitro Robo1/2 knockout experiments in mouse and human granulosa cells. We also found that ovarian angiogenesis was enhanced by a partial lack of Robo1/2 genes. In summary, our data suggest that the Slit/Robo pathway can impact follicle development and atresia by influencing granulosa cell apoptosis.
authors.affiliation: Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Jiangchao
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Reproductive Medicine Center, Guangdong General Hospital, Guangzhou 515006, China.
authors.forename: Renli
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Reproductive Medicine Center, Guangdong General Hospital, Guangzhou 515006, China.|Southern Medical University, Guangzhou 510515, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiwen
authors.initials: X
authors.lastname: Hu
authors.affiliation: Reproductive Medicine Center, Guangdong General Hospital, Guangzhou 515006, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Jiayuan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: He
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology &Embryology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, Division of Histology &Embryology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Vascular Biological Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D005260:Female; D005298:Fertility / Q000235:genetics; D015870:Gene Expression; D006107:Granulosa Cells / Q000378:metabolism*; D006728:Hormones / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D006080:Ovarian Follicle / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D006728:Hormones; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C498888:Robo2 protein, mouse