Human Reproduction, Vol. 17, No. 10, 2678-2685,
October 2002
© 2002 European Society of Human Reproduction and Embryology
Ageing-associated aberration in meiosis of oocytes from senescence-accelerated mice
1 Department of Obstetrics and Gynecology, Brown University, Women and Infants Hospital, Providence, RI 02905 and 2 Laboratory for Reproductive Medicine, Marine Biological Laboratory, 7 MBL St, Woods Hole, MA 02543, USA
BACKGROUND: The senescence-accelerated mouse (SAM) has been shown to exhibit ageing-associated mitochondrial dysfunction and oxidative stress, and early decline in fertility. METHODS: We compared meiotic progression of germinal vesicle oocytes between young (2–3 months) and old (10–14 months) SAM mice using triple immunostaining and fluorescence microscopy as well as Pol-Scope imaging. RESULTS: At 8–9 h of in-vitro maturation (IVM), most young SAM oocytes (86%, 32/37) were at meiosis I (MI) stage, with chromosomes aligned in the mid-region of MI spindles, whereas disrupted MI spindles and/or chromosome misalignments (45%, 18/40) and a few oocytes (20%, 8/40) with abnormal MII spindles were found in old SAM oocytes. At 15–17 h of IVM, old SAM oocytes, despite errors at MI stage, extruded a first polar body at an incidence of 88% (n = 85), which did not differ from that (92%, n = 106) of young SAM oocytes. However, oocytes from old SAM (64%, 32/50) showed aberrant MII, with chromosome misalignment and dispersal, in contrast to normal MII in most young SAM oocytes (87%, 65/75), showing chromosome alignment at the metaphase plate of MII spindles. Moreover, Pol-Scope imaging non-invasively detected disrupted or absent visible spindles and possibly aberrant chromosome alignment. CONCLUSIONS: Spindle disruption and/or chromosome misalignments at both MI and MII are associated with maternal ageing in the SAM mouse. Our findings also suggest that meiotic division lacks a competent checkpoint for spindle integrity and chromosome alignment during reproductive ageing-associated oocyte senescence.
Key words: ageing/meiosis/oocyte/Pol-Scope/senescence-accelerated mouse
3 To whom correspondence should be addressed. E-mail: dkeefe{at}wihri.org
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