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.

Conversion of androgen to estrogen by the rat fetal and neonatal female gonad: effects of dcAMP and FSH.

Female gonads of fetal (on days 14.5, 16.5, 18.5 and 20.5 postcoitum) and neonatal rats (on days 4.5 and 8.5 postpartum) were cultured in Medium 199 in the presence of [3H]testosterone and the conversion into [3H]estrone and [3H]estradiol was estimated. Formation of both estrogens was found in all fetal and neonatal ovaries explanted in control medium. Dibutyryl cAMP (1 mM) had a clear-cut stimulatory effect as early as 16.5 days postcoitum, but had little or no effect at 8.5 days postpartum. In contrast, ovine or rat FSH (0.3 or 1 microgram/ml, respectively) increased the aromatase activity only from 20.5 days postcoitum. The effects of FSH and dibutyryl cAMP were more obvious after preculture for 48 h in control medium. These results indicate that: a biochemical sex differentiation, revealed by the difference in aromatase activity levels between ovaries and testes or other tissues occurs in female gonads as early as 14.5 days postcoitum; aromatase activity in the ovaries increases markedly after birth; functional FSH receptors are absent before 20.5 days postcoitum in the ovaries.