Human First Trimester Fetal Ovaries Express Oncofetal Antigens and Steroid Receptors

Abstract

Objective: To document the expression of oncofetal antigens and steroid receptors in first trimester human fetal ovaries and to determine the effect of advancing gestation on expression patterns.

Methods: Fetal gonads were collected from surgical tenninations of pregnancy, and fetal sex was determined by fluorescence in situ hybridization. Immunocytochemical analysis was performed on paraffin sections of microdissected fetal ovaries using antibodies to carcinoembryonic antigen (CEA), placental alkaline phosphatase (PLAP), hCG, alpha fetoprotein (AFP), CA 125, estrogen receptor (ER) and progesterone receptor (PR) in 12 first trimester human fetal ovaries. Expression was quantified objectively by measuring percentage area of immunoreactivity (PAI) on whole sections of the ovary using an interactive image analysis system. Two pathologists, blinded to the antibodies used, independently viewed and scored all sections.

Results: PLAP, PR, ER and CEA were expressed in all 12 ovaries (31%, 28%, 21%, and 16% mean PAI, respectively). A diffuse staining pattern was observed at 8 weeks' gestation, which was more focal and confined to the cortical regions of the gonad by 12 weeks' gestation. Putative primordial germ cells were positive of PLAP, PR and ER but rarely for CEA. The expression (PAI) of PLAP and PR was unchanged during the first trimester, whereas that of ER decreased from 28% to 12%. The expression of CEA and hCG decreased from 8 to 11 weeks and then increased markedly by 13 weeks. AFP had a medullary distribution and was expressed in nine of 12 ovaries (mean PAI 18%). CA 125 expression was minimal or undetected.

Conclusion: PLAP, ER and PR were the most extensively expressed protein antigens, particularly in fetal ovarian cortex. These variable patterns of expression suggest levels of differentiation in the immature first trimester human fetal ovary.