Fibrillins in adult human ovary and polycystic ovary syndrome: is fibrillin-3 affected in PCOS?
Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive age. Although genetic linkage analyses have demonstrated a susceptibility locus for PCOS mapping to the fibrillin-3 gene, the presence of fibrillin proteins in normal and polycystic ovaries has not been characterized. This study compared and contrasted fibrillin-1, -2, and -3 localization in normal and polycystic ovaries. Immunohistochemical stainings of ovaries from 21 controls and 9 patients with PCOS were performed. Fibrillin-1 was ubiquitous in ovarian connective tissue. Fibrillin-2 localized around antral follicles and in areas of folliculolysis. Fibrillin-3 was present in a restricted distribution within the specialized perifollicular stroma of follicles in morphological transition from primordial to primary type [transitional follicles (TFs)]. Fibrillin-1 and -2 stainings of PCOS ovaries were similar to those of the controls. However, in eight of the nine PCOS ovaries, there was a decrease in the number of TFs associated with fibrillin-3, including no staining in five PCOS samples; decreased number of fibrillin-3-associated TFs/mm(2) was confirmed by quantitative analysis. Our findings support a role for fibrillin-3 in the pathogenesis of PCOS and suggest fibrillin-3 may function in primordial to primary follicle transition. We propose that loss of fibrillin-3 during folliculogenesis may be an important factor in PCOS pathogenesis.
Jordan
C Diana
CD
Department of Pathology, University of Washington Medical Center, Seattle, WA 98195, USA. cdjordan@u.washington.edu
Bohling
Sandra D
SD
Charbonneau
Noe L
NL
Sakai
Lynn Y
LY
D000293:Adolescent; D000328:Adult; D005260:Female; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D006080:Ovarian Follicle / Q000378:metabolism; D010053:Ovary / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism; D055815:Young Adult; D054392:Adipokines
D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human; C493782:FBN3 protein, human