Maturation and apoptosis of human oocytes in vitro are age-related.

OBJECTIVE To study the morphological changes of apoptotic oocytes, and rates of in vitro maturation and apoptosis of human oocytes in relation to age. DESIGN Prospective comparative study. SETTING Reproductive medicine center. PATIENT(S) Women undergoing surgery for ovarian cysts. INTERVENTION(S) Oocytes were incubated in Ham's F-10 medium with 15% fetal cord serum (FCS) for 32 to 120 hours and were examined under inverted microscope every 6 to 8 hours. MAIN OUTCOME MEASURE(S) Oocyte maturation and apoptosis, Fas antigen. RESULT(S) The morphologic changes characteristic of apoptosis oocytes were shrinkage, or the occurrence of cytoplasmic condensation, membrane blebbing, fragmentation of the oocyte into "apoptotic" bodies of unequal size, or internucleosomal DNA cleavage as shown by TUNEL. The maturation rates of oocytes were highest in those from women aged 21 to 30 years, and lowest in those aged 41 to 50 years. Apoptosis occurred in 17.1% (age group 21 to 30 years), 37. 7% (31 to 40 years), and 52.3% (41 to 50 years). The rate of apoptosis of human immature oocytes cultured in vitro was significantly higher in those from older women who were 41 to 50 years old than in those women 21 to 40 years old. Fas antigen was found to be present on apoptotic oocyte membranes. CONCLUSION(S) The developmental potential of oocytes from older women decreased in vitro in a manner similar to that seen in vivo. DNA fragmentation in oocytes associated with apoptotic death might be one of the reasons for poor oocyte quality and lower fertility in older women. Fas antigen in the oocyte presumably mediates apoptosis.

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