Induction of proliferation in the primate ovarian surface epithelium in vivo.
BACKGROUND
Epithelial ovarian cancer (EOC) is the primary ovarian malignancy affecting women. Proposed etiologies of EOC resist direct testing due to the absence of a suitable animal model, as EOC affects only primates, not other mammals. The role of proliferation in ovarian surface epithelium (OSE) transformation has been suggested but not demonstrated, nor has OSE proliferation been widely reported. We selected the rhesus macaque as a model to evaluate the unique primate OSE in vivo, and to determine whether it can undergo proliferative repair, which may relate to EOC etiology.


METHODS
Macaque ovaries were collected at three stages of the cycle. Very late luteal phase ovaries were gently brushed during laparoscopy to remove a portion of the OSE, and ovaries (< or =3 per group) were collected 1-4 days later. Ovary samples were also collected from 10 women aged 33-74 years. Ovarian tissue sections were probed with OSE markers (keratin, beta-catenin, E- and N-cadherin), proliferation markers [proliferating cell nuclear antigen (PCNA), phosphorylated histone H3 (phospho-H3), and phosphorylated Retinoblastoma (pRb)], or labels of collagen and basement membrane.


RESULTS
Brushing partially removed the OSE; did not cause tissue damage/adhesions; elevated the frequency of PCNA, phospho-H3 and pRb in the residual OSE, marking as many as 10-50% of cells in brushed regions (unbrushed areas contained <0.1% positive cells), and; did not induce proliferation in underlying stromal cells.


CONCLUSIONS
The OSE can undergo proliferative repair, and thus its normal regulation could contribute to EOC etiology.
Wright
Jay W
JW
Division of Reproductive Sciences, Oregon National Primate Research Center, Beaverton, OR 97006, USA. wrightj@ohsu.edu
Pejovic
Tanja
T
Fanton
John
J
Stouffer
Richard L
RL
D000328:Adult; D000368:Aged; D000818:Animals; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta; D008875:Middle Aged; D010053:Ovary / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D017154:Stromal Cells / Q000473:pathology; D014945:Wound Healing
D006657:Histones; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein