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oocyte that showed gemlinal vesicle breakdown (i. e. resumption of meiosis) and<br />

cumulus dispersion, However, ovulation had not completed because no ova were<br />

found in the oviducts (Figure 3C). In two other animals, growing preantral and large<br />

antral follicles were present, in the absence of indications of previous ovulations<br />

(Figure 3D). These ovaries were similar in appearance to the ovaries of the first<br />

anovulatory group, but the follicles and interstitium in these animals were<br />

developed much further. The ovaries from wild type females showed a normal<br />

picture, i, e. preantral and large antral follicles with new corpora lutea and ova in the<br />

oviduct (Figure 3F).<br />

Overall, these observations indicate a broad range of ovarian dysfunction in TTD<br />

mice ranging from complete anovulation, via intact follicular growth to<br />

preovulatory stages to sporadic, normal ovulation. Because fertility could very well<br />

be a function of physical fitness of the individual, it is important to note that no<br />

strict correlation was found between severeness of cachexia (as apparant from<br />

bodyweight) and degree of anovulation. The heterogeneity in ovarian dysfunction as<br />

well as other TID features may be due to the mixed 129-C57BLl6 background of<br />

the mice. Whether acyclic TID females resemble reversible infertility as in anorecic<br />

females or irreversible infertility as in mammalian menopauze awaits further<br />

analysis.<br />

We also compared fertility of a group of six TID males to six wild-type littelmates<br />

by mating to wild-type females. At least up to seven months of age, TTD males<br />

displayed normal fertility.<br />

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