Molecular Human Reproduction, Vol 4, 483-489, Copyright © 1998 by Oxford University Press
A Tsafriri, M Popliker, R Nahum and Y Beyth
In-vitro studies on mouse oocytes have shown that human follicular fluid
and bull testes contain an activity which partially overrides the
inhibitory action of hypoxanthine on meiosis. This activity was ascribed to
two closely related sterols, subsequently named meiosis- activating sterols
(MAS). We have used a potent inhibitor of sterol synthesis, ketoconazole,
in order to test in vivo and in vitro whether MAS play a necessary
physiological role in the resumption of meiosis in the rat. When
administered systemically, ketoconazole (8.3-16.6 mg/rat) suppressed
ovulation by 40%. Local unilateral administration of the drug into the
ovarian bursa (1.25 mg/bursa) resulted in 75% inhibition of ovulation in
comparison with the contralateral ovary. All the ovulated ova in the
oviduct were mature. Histological examination of the ketoconazole-treated
ovaries revealed mature oocytes trapped in follicles which failed to
ovulate. Furthermore, extraction of oocytes from the large follicles of
such ovaries revealed that 79% of them were mature. Addition of
ketoconazole (0.0001-0.01 mM) to the culture medium did not affect
significantly the spontaneous maturation of rat oocytes. However,
ketoconazole at a higher concentration (0.1 mM) caused the degeneration of
oocytes. Ketoconazole (0.01 mM) did not affect luteinizing hormone
(LH)-stimulated oocyte maturation in explanted preovulatory follicles, even
though it inhibited follicular progesterone production to levels below the
hormone-free control follicles. At higher levels, ketoconazole caused the
degeneration of follicles and the enclosed oocytes. In conclusion, using a
potent inhibitor of MAS we have failed to confirm the suggested obligatory
role of MAS in the resumption of meiosis in the rat both in vivo and in
vitro.
JOURNAL ARTICLE
Effects of ketoconazole on ovulatory changes in the rat: implications on the role of a meiosis-activating sterol
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
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