The antiestrogen ICI 182,780 induces early effects on the adult male mouse reproductive tract and long-term decreased fertility without testicular atrophy.
BACKGROUND
Estrogen receptors (ER) have important physiological roles in both the female and male reproductive systems. Previous studies using the estrogen receptor-alpha knockout mouse (alphaERKO) or antiestrogen treatment in adult rodents have shown that ERalpha is essential for normal function of the male reproductive tract. In the present study, time-response effects of the antiestrogen ICI 182,780 were determined to better understand ERalpha function in the adult male.


METHODS
Adult male mice, 30 days old, were injected subcutaneously with ICI 182,780 (5 mg) once per week for 17 weeks. Tissues were fixed by vascular perfusion to study the time responses from day 2 to 125 post treatment.


RESULTS
No difference was seen in body weight due to treatment. Testis weight was decreased 18% on day 59 and 21.4% on day 125. Other significant treatment-related effects included the following: 1) dilation of rete testis and efferent ductule lumen; 2) decreased height of the rete testis and efferent ductule epithelium; 3) decreased height of the supranuclear epithelial cytoplasm in efferent ductules; 4) decreased height of the efferent ductule epithelial microvilli, particularly in the proximal ductules; 5) decrease in the PAS-positive granules and endocytotic vesicles in nonciliated epithelial cells of efferent ductules; 6) capping and vesiculation of narrow cells in the initial segment of the epididymis; 7) accumulation of PAS-positive granules in apical cells of the caput epididymis; 8) increase in lysosomal granules in clear cells of the corpus and cauda epididymis; 9) limited induction of atrophic seminiferous tubules and abnormal spermatogenesis; and 10) decreases in the concentration of cauda sperm, progressive sperm motility and decreased fertility.


CONCLUSIONS
Antiestrogen treatment of the pubertal male mouse resulted in reproductive effects similar to those observed in the alphaERKO mouse as early as day 4; however, testis weight did not increase substantially and total atrophy was not observed with extended treatment.
Cho
Hyun Wook
HW
Reproductive Biology & Toxiology, Veterinary Biosciences, University of Illinois, 2001 S, Lincoln, Urbana, IL 61802, USA. hwcho@sunchon.ac.kr
Nie
Rong
R
Carnes
Kay
K
Zhou
Qing
Q
Sharief
Noaman A Q
NA
Hess
Rex A
RA
D000818:Animals; D003594:Cytoplasmic Granules / Q000187:drug effects; D004822:Epididymis / Q000187:drug effects / Q000648:ultrastructure; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D020847:Estrogen Receptor Modulators / Q000494:pharmacology* / Q000633:toxicity; D047628:Estrogen Receptor alpha; D005260:Female; D005313:Fetal Death / Q000209:etiology; D005327:Fetal Resorption / Q000209:etiology; D000077267:Fulvestrant; D007248:Infertility, Male / Q000139:chemically induced* / Q000473:pathology; D007279:Injections, Subcutaneous; D008247:Lysosomes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008871:Microvilli / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D018812:Paternal Exposure; D011897:Random Allocation; D011960:Receptors, Estrogen / Q000187:drug effects / Q000502:physiology*; D012152:Rete Testis / Q000187:drug effects / Q000648:ultrastructure; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000648:ultrastructure; D012741:Sexual Maturation; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol