Related Experiment Videos
Effects of antiestrogens on adult and neonatal mouse reproductive organs
Abstract:
Estrogenic potencies of various antiestrogens, including keoxifene (Kx) and trifluoperazine (Tfp), on reproductive tracts of ovariectomized adult mice, and effects of neonatal Kx and Tfp on reproductive organs were studied in C57BL/Tw mice. In adult ovariectomized mice, weight, DNA, and protein of the uterus and vagina were increased by 3 daily injections of 100 micrograms clomiphene, tamoxifen (Tx), and nafoxidine, and of 1 microgram estradiol-17 beta (E), but not by Kx. Antiestrogenic potency of Kx was studied in adult mice given injections of E. Kx significantly suppressed the E-induced increase in weight, DNA, and protein in the uterus and vagina. Tfp (20 micrograms), known as a tranquilizer and an antiestrogen, had no estrogenic effect on either organ. Male and female mice given 5 daily injections of Kx or Tfp from the day of birth were examined at 30, 40, and 60 days of age. Weights of testis, epididymis, and seminal vesicle in neonatally Kx-treated mice were significantly lower than in controls at 30 and 40 days. Spermatozoa were not formed in the seminiferous tubules of Kx-treated mice, although spermatogenesis occurred at 60 days. In neonatally Kx-treated females, weight of the uterus at 60 days and of the vagina at 40 and 60 days was significantly lower than in controls. Corpora lutea were absent from the ovaries of Kx-treated females. In neonatally Tfp-treated mice of both sexes at all ages examined, no differences were found in organ weights or histology, other than lower spermatogenic indices at 40 and 60 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Keoxifene (Kx) acts as an antiestrogen in adult mice, suppressing estrogen effects on reproductive organs. Neonatal Kx exposure significantly impaired reproductive development in both male and female mice.
Area of Science:
- Endocrinology
- Reproductive Biology
- Pharmacology
Background:
- Estrogenic and antiestrogenic compounds are crucial in reproductive health research.
- Understanding the long-term effects of developmental exposure to these agents is vital.
Purpose of the Study:
- To evaluate the estrogenic and antiestrogenic potencies of keoxifene (Kx) and trifluoperazine (Tfp) on adult mouse reproductive tracts.
- To investigate the effects of neonatal exposure to Kx and Tfp on reproductive organ development.
Main Methods:
- Adult ovariectomized mice received daily injections of antiestrogens or estradiol-17 beta (E).
- Neonatal mice (male and female) were administered daily injections of Kx or Tfp from birth.
- Reproductive organ weights, DNA, protein content, and histology were assessed at various ages.
Main Results:
- In adult mice, Kx demonstrated antiestrogenic activity by suppressing E-induced uterine and vaginal growth.
- Neonatal Kx exposure led to significantly reduced weights of testes, epididymis, and seminal vesicles in males, with impaired spermatogenesis.
- Neonatal Kx exposure in females resulted in lower uterine and vaginal weights and absent corpora lutea.
Conclusions:
- Keoxifene exhibits significant antiestrogenic effects in adult mice and causes developmental reproductive toxicity upon neonatal exposure.
- Trifluoperazine showed minimal estrogenic or antiestrogenic effects and no significant developmental toxicity in this study.
- These findings highlight the differential impact of Kx based on exposure timing, with critical implications for reproductive development.