title: The role of bone morphogenetic protein 6 in accumulation and regulation of neutrophils in the human ovary.
abstract: Bone morphogenetic protein (BMP) cytokine is known to regulate ovulation, as BMP-6 null mice exhibit a decrease in the number of ovulatory follicles without effect on either the morphology or the dynamics of follicular development. In the present study, the role of BMP-6 in ovulatory process was investigated using human granulosa-lutein cells (GCs). Granulosa-lutein cells, obtained from in vitro fertilization patients, were cultured with BMP-6 followed by RNA extraction. The neutrophil-chemotactic activity of the supernatant of cultured GC was investigated. Bone morphogenetic protein 6 significantly increased growth-regulated oncogene α (GRO-α) messenger RNA (mRNA) and protein expression in GC. In the neutrophil-chemotaxis assay, the GC supernatant cultured with BMP-6 attracted more neutrophils than control samples, which was negated with anti-GRO-α neutralizing antibody. Bone morphogenetic protein 6 also suppressed the relative expression of the protease inhibitors, secretory leukocyte peptidase inhibitor, and whey acid protein 14 mRNA in GC. Bone morphogenetic protein 6 might play a role in ovulation by increasing the accumulation of neutrophils in the ovulatory follicle and suppressing the effect of protease inhibitors.
authors.affiliation: 1Department of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Akiyama
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshino
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Osuga
authors.forename: Jia
authors.initials: J
authors.lastname: Shi
authors.forename: Masashi
authors.initials: M
authors.lastname: Takamura
authors.forename: Miyuki
authors.initials: M
authors.lastname: Harada
authors.forename: Kaori
authors.initials: K
authors.lastname: Koga
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hirota
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hirata
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujii
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.forename: Shiro
authors.initials: S
authors.lastname: Kozuma
mesh_terms: D055418:Bone Morphogenetic Protein 6 / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D010053:Ovary / Q000166:cytology* / Q000502:physiology*; D017697:Premenopause / Q000502:physiology
chemical_list: C525816:BMP6 protein, human; D055418:Bone Morphogenetic Protein 6
keywords: BMP; neutrophil; ovulation