Controlled Neonatal Exposure to Estrogens: A Suitable Tool for Reproductive Aging Studies in the Female Rat1

Abstract

The present study was designed to determine whether the modification of exposure time to large doses of estrogens provided a reliable model for early changes in reproductive aging. Silastic implants containing estradiol benzoate (EB) in solution were placed into 5-day-old female Wistar rats and removed 1 day (Ei1 group) or 5 days (Ei5) later. In addition, 100 micrograms [corrected] EB dissolved in 100 microliters corn oil was administered s.c. to another group (EI). Control rats received either vehicle implants or 100 microliters corn oil. Premature occurrence of vaginal opening was observed in all three estrogenized groups independently of EB exposure. However, females bearing implants for 24 h had first estrus at the same age as their controls and cycled regularly, and neither histological nor gonadal alterations could be observed at 75 days. Interestingly, they failed to cycle regularly at 5 mo whereas controls continued to cycle. On the other hand, the increase of EB exposure (Ei5, EI) resulted in a gradual and significant delay in the onset of first estrus and in a high number of estrous phases, as frequently observed during reproductive decline. At 75 days, the ovaries of these last two groups showed a reduced number of corpora lutea and an increased number of large follicles. According to this histological pattern, ovarian weight and progesterone (P) content gradually decreased whereas both groups showed higher estradiol (E2) content than controls. This resulted in a higher E2:P ratio, comparable to that observed in normal aging rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal exposure to estradiol in rats influences neuroactive steroid concentrations, GABAA receptor expression, and behavioral sensitivity to anxiolytic drugs

“…In addition to its previously demonstrated effect on peripheral steroidogenic tissue (Rodriguez et al. 1993), we have now shown that the administration of β‐estradiol 3‐benzoate to female neonates induced pronounced decreases in the concentrations of progesterone and its metabolite allopregnanolone in the cerebral cortex that were apparent in both juvenile (3 weeks) and adult (2–6 months) animals.…”

“…1993), we have now shown that the administration of β‐estradiol 3‐benzoate to female neonates induced pronounced decreases in the concentrations of progesterone and its metabolite allopregnanolone in the cerebral cortex that were apparent in both juvenile (3 weeks) and adult (2–6 months) animals. In contrast, the brain and plasma levels of 17β‐estradiol measured in adult rats were not affected by the neonatal administration of β‐estradiol 3‐benzoate, although a marked increase in estradiol plasma levels 24 h after injection of estradiol benzoate, that remained higher 10 days after injection has been previously observed (Rodriguez et al. 1993; Amateau et al.…”

“…1975) and consequently results in reduced ovarian and plasma concentrations of progesterone (Handa et al. 1985; Rodriguez et al. 1993).…”

“…Females were mated with males at regular intervals. On the day of birth (day 0), the male pups were removed from the litter and the female offspring were injected s.c. with 50 μL of sesame oil (controls) or with 10 μg of β‐estradiol 3‐benzoate in 50 μL of sesame oil (Rodriguez et al. 1993; Solum and Handa 2002).…”

Chronic treatment with the nitric oxide synthase inhibitor, L-NAME, attenuates estradiol-mediated improvement of learning and memory in ovariectomized rats

“…The average lifetime of Wistar rats is about 30-31 months,52,53 and their puberty begins at 37-45 postnatal days 54-56. Therefore, the 8-week-old rats that were used in the present study were young animals.…”