Jonathan Van Blerkom1,2,3 and Patrick Davis1,2
1Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309 and 2Colorado Reproductive Endocrinology, Rose Medical Center, Denver, CO 80220, USA
3To whom correspondence should be addressed at: Department of Molecular, Cellular and Developmental Biology University of Colorado, Boulder, CO 80309, USA. E-mail:
The effects of four rounds of ovarian stimulation spaced 1-6 weeks apart on the normality of methaphase II (MII) spindle formation, chromosomal allignment and cytoplasmic organization were examined in intact ovulated mouse oocytes and at MII for oocytes obtained at the germinal vesicle stage from the same ovaries and matured in vitro.
The terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling assay was used to identify DNA strand breaks in chromosomes, and histological studies of ovaries between and at each round of ovarian stimulation were performed.
The results demonstrate a progressive and significant increase in the frequency of spindle defects with each round of ovarian stimulation, including those spaced weeks apart.
Oocytes with spindle defects were also characterized by the occurrence of detached chromosomes and cytoplasmic asters.
In contrast, in-vitro matured oocytes derived from the same ovaries were normal.
No evidence of DNA strand breaks with repeated rounds of ovarian stimulation was detected in ovulated or in-vitro matured oocytes.
The development and persistence of nodules of hypertrophied granulosa in regions where follicular growth occurs suggest that a progressively increasing proportion of oocytes in the ovulatory pathway may expericne an intrafollicular millieu that has negative consequences for competence.
The results are discussed with respect to ovarian and oocyte biological ageing and possible adverse implications for human oocyte competence with repeated hyperstimulation.
Abstract, Human Reproduction Vol.16, No.4 pp. 757-764, 2001
