[Combined use of steroid hormone and low dose gossypol for antifertility and its mechanism in rats].
OBJECTIVE
To study the feasibility and the morphological mechanism of combined use of steroid hormone (methyltestosterone and ethinyl estradiol) and low dose gossypol for antifertility in adult Wistar rats.


METHODS
We used methyltestosterone 20 mg/(kg.d), ethinyl estradiol 100 micrograms/(kg.d), and gossypol 12 mg/(kg.d) to feed male rats for 6 weeks via gastric intubation to induce infertility, then used gossypol 12 mg/(kg.d) alone for another 12 weeks to maintain infertility. Testicular sperm counts, cauda epididymal sperm motility, and sperm silver staining were used to determine infertility and morphology of sperm at the end of the two phases. Testicular morphology of the rats was observed from HE and PAS staining of paraffin sections. F1 generation of the rats would be examined in a series of behavioral tests after their 6-week recovery periods.


RESULTS
There was no substantial change in testicular sperm counts of drugs-treated rats both for 6 weeks and 6 plus 12 weeks compared with that of control. But cauda epididymal sperm motility of drugs-treated rats went down to zero at the end of two phrases. The result of sperm silver staining showed that epididymal sperm were all deleterious of either segregation of sperm nucha from sperm head, or separation in annular granule of sperm tail. The observation of testicular morphology suggested that spermatogenesis is only partially affected. The ratios of stages II-III (9.3 +/- 3.4)% and stages IX-X (3.6 +/- 0.6)% were remarkably dropped, but that of stages IV-VI (36.7 +/- 5.0)% obviously ascended comparing with (26.8 +/- 1.7)%, (6.0 +/- 0.4)%, (24.5 +/- 2.7)% of control at the end of 6 plus 12 weeks. Moreover, no adverse effect was found in viscera tissue sections.


CONCLUSIONS
Steroid hormone made the procedure of spermatogenesis slower and low dose gossypol caused all sperm lose their activity in epididymis. Both affect the process of spermatogenesis from different endpoints and successfully induce infertility in short term. Low dose gossypol not only executes its antifertility function in epididymis, but also affects the quality of spermatozoal production in testis by impacting the procedures of both acrosomal formation and spermatozoal elongation, so it can completely maintain infertility in long term. The infertility was reversible that the infertile rats can be recovery in about 6 weeks. Their F1 generation were proved to be normal through a set of behavioral tests.
Wang
L
L
Department of Histology and Embryology, Institute of Basic Medical Sciences, CAMS, PUMC, Beijing 100005, China.
Ye
W
W
Liu
X
X
Guo
Y
Y
D000284:Administration, Oral; D000818:Animals; D003272:Contraceptive Agents, Male / Q000008:administration & dosage* / Q000494:pharmacology; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D006072:Gossypol / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013091:Spermatogenesis / Q000187:drug effects*; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology
D003272:Contraceptive Agents, Male; D013739:Testosterone; D004997:Ethinyl Estradiol; D006072:Gossypol