title: Gap junctions are essential for murine primordial follicle assembly immediately before birth.
abstract: The reserve of primordial follicles determines the reproductive ability of the female mammal over its reproductive life. The primordial follicle is composed of two types of cells: oocytes and surrounding pre-granulosa cells. However, the underlying mechanism regulating primordial follicle assembly is largely undefined. In this study, we found that gap junction communication (GJC) established between the ovarian cells in the perinatal mouse ovary may be involved in the process. First, gap junction structures between the oocyte and surrounding pre-granulosa cells appear at about 19.0 dpc (days post coitum). As many as 12 gap junction-related genes are upregulated at birth, implying that a complex communication may exist between ovarian cells, because specifically silencing the genes of individual gap junction proteins, such as Gja1, Gja4 or both, has no influence on primordial follicle assembly. On the other hand, non-specific blockers of GJC, such as carbenoxolone (CBX) and 18α-glycyrrhetinic acid (AGA), significantly inhibit mouse primordial follicle assembly. We proved that the temporal window for establishment of GJC in the fetal ovary is from 19.5 dpc to 1 dpp (days postpartum). In addition, the expression of ovarian somatic cell (OSC)-specific genes, such as Notch2, Foxl2 and Irx3, was negatively affected by GJC blockers, whereas oocyte-related genes, such as Ybx2, Nobox and Sohlh1, were hardly affected, implying that the establishment of GJC during this period may be more important to OSCs than to oocytes. In summary, our results indicated that GJC involves in the mouse primordial follicle assembly process at a specific temporal window that needs Notch signaling cross-talking.
authors.affiliation: State Key Laboratory of Agro-BiotechnologyCollege of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Teng
authors.affiliation: State Key Laboratory of Agro-BiotechnologyCollege of Biological Science, China Agricultural University, Beijing 100193, China wangcam@cau.edu.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agro-BiotechnologyCollege of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agro-BiotechnologyCollege of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Agro-BiotechnologyCollege of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Agro-BiotechnologyCollege of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Wanbao
authors.initials: W
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Agro-BiotechnologyCollege of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Lizhao
authors.initials: L
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Agro-BiotechnologyCollege of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Agro-BiotechnologyCollege of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Agro-BiotechnologyCollege of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000187:drug effects / Q000235:genetics; D018031:Connexin 43 / Q000037:antagonists & inhibitors / Q000235:genetics; D017630:Connexins / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D036801:Parturition / Q000502:physiology*; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000494:pharmacology; D000097006:Gap Junction alpha-4 Protein
chemical_list: D018031:Connexin 43; D017630:Connexins; D034741:RNA, Small Interfering; D000097006:Gap Junction alpha-4 Protein; C543076:GJA1 protein, mouse