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Irreversible effects of neonatal exposure to p-tert-octylphenol on the reproductive tract in female rats.

Abstract：

:It has been known for many years that administration of androgens or estrogens at critical periods of development in mammals causes severe long-term effects on the endocrine/genital systems. The environmental pollutant p-tert-octylphenol (OP) possesses a weak but clear estrogen agonist activity in in vitro and in vivo studies. In the present study, effects of neonatal exposure to OP on the reproductive tract of female rats were investigated. Newborn female pups were injected with 100 mg/kg OP subcutaneously within 24 h after birth. Administration was repeated every other day until postnatal day 15 (total of eight doses). Before weaning, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) remained at low levels during OP exposure, although the serum FSH peak and the high LH level were obvious in the controls. Histologically, inhibition of uterine gland genesis was apparent. The day of vaginal opening was about 4 days earlier in OP-treated animals than in controls. Persistent estrus was consistently observed in OP-treated animals. Atrophic and polycystic ovaries without corpora lutea showed anovulation. In the endometrium, cell-proliferative activity and cell-death were increased and decreased, respectively, and expression of estrogen receptor alpha mRNA was apparent by in situ hybridization. Unexpectedly, endometrial hyperplasias appeared at 8 weeks of age. After ovariectomy, vaginal smears immediately became of castration type and the uterus was atrophied. These results suggested that neonatal exposure to a high dose of OP alters developmental hormonal secretion presumably due to a hypothalamo-pituitary-ovarian disorder, with accelerated vaginal opening, subsequent persistent estrus, and uterine endometrial hyperplasia. The changes in the uterus and vagina are ovary-dependent.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Katsuda S,Yoshida M,Watanabe G,Taya K,Maekawa A

doi

10.1006/taap.2000.8940

subject

Has Abstract

pub_date

2000-06-15 00:00:00

pages

217-26

issue

3

eissn

0041-008X

issn

1096-0333

pii

S0041008X00989403

journal_volume

165

pub_type

杂志文章

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