Effects of Busulfan on Ovarian Folliculogenesis, Steroidogenesis and Anti-müllerian Activity of Rat Neonates

Pregnant rats were injected with busulfan on day 12 or 18 of gestation and the ovaries of 5- and 10-day-old neonates were compared with control ones in terms of 1) folliculogenesis, 2) production of estradiol-17 beta and estrone in vitro, 3) aromatase and 3 beta-hydroxysteroid dehydrogenase/isomerase (3 beta-HSD) activities, and 4) anti-müllerian hormone. Injection of busulfan on day 12 led to a reduction in the number of germ cells and follicles, delayed the maturation of antral follicles and lowered estrogen production and aromatase and 3 beta-HSD activities. Anti-müllerian activity, present in ovaries from 10-day-old controls, was also depressed in busulfan-treated rats. No obvious effects were observed when busulfan was injected on day 18. Estrogen biosynthesis could be stimulated by gonadotropins at day 10 post-partum, indicating the presence of functional receptors to LH and/or FSH. These relationships are interpreted as indicating that ovarian cells retain their capacity to respond to hormonal challenge despite the morphological impairment induced by busulfan. Other factors which possibly interfere with ovarian activity in busulfan-treated rats are discussed.