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Summary.
The effect on the testis of some forty-two water-soluble salts of metals and rare earths was investigated in rats and mice. In general, a single intratesticular injection caused varying degrees of degeneration of the seminiferous epithelium and the interstitium. Thirty-five of the salts tested exerted some degree of antitesticular effect. A single subcutaneous injection was ineffective but continuous administration by the same route caused selective spermatogenic arrest with nine salts. Some of the salts caused aspermia of the recipient animals; others disintegrated the residual spermatozoa in the ductus deferens by separation of the head and tail. The possible mechanism of action of the salts is discussed.
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Summary. A single oral administration of centchroman (1·25 mg/kg) to adult female rats within 24 h of mating induced slight acceleration in the rate of transport of embryos through the oviducts. The compound did not seem to produce any deleterious effect on preimplantation embryonic development since well organized and apparently normal embryos were collected from the genital tract up to Day 12 of pregnancy. The recovery rate of embryos from centchroman-treated rats was, however, significantly reduced after Day 4 of pregnancy. There was some stimulation in the rate of cleavage of embryos and morula to blastocyst transformation, but retardation in the shedding of the zona pellucida. The rate of blastocyst formation was not altered when 6–8-cell embryos collected from the oviducts of control rats were transferred to the uteri of control or centchroman-treated females. A delay in zona shedding was observed in the centchroman-treated recipients.
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Summary. 'Tube-locked' morulae and blastocysts were recovered from the ampulla of the oviduct of centchroman-treated mice between Days 4 and 12 post coitum and transferred to the uteri of pseudopregnant female mice. Pregnancy and implantation rates were lower and the post-implantation resorption rate was higher in the treated than in the control group. There was little difference in the pregnancy or implantation rates between embryos recovered on Days 4 or 12 post coitum, but the resorption rate increased with increasing duration of embryos in the oviducts and was 100% for the Day-12 embryos. The resorption rate was similar even when these embryos were transferred to the sterile uterine horn of unilaterally pregnant mice. Centchroman did not produce any deleterious effect on embryos which survived until Day 19 of pregnancy in foster mothers. The average fetal weight was also comparable to those of control fetuses.
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The duration of the anti-implantation action of a single oral post-coital dose (1.25 mg kg−1) of a triphenylethylene anti-oestrogen, centchroman, was determined in adult rats. The effects of centchroman were compared with those of tamoxifen. In rats undergoing delay, centchroman administered orally on day 7 post-coitum prevented the induction of implantation of delayed blastocysts by an implantation inducing dose (1 μg per rat, s.c.) of oestrone which was administered earlier than 120 h after centchroman treatment. In tamoxifen (0.2 mg kg−1, orally) pretreated rats, oestrone administered at 144 h or later induced implantation. In cyclic rats treated with centchroman at intervals of 168 h and mated with males of proven fertility, implantation was prevented only when the interval between centchroman treatment and nidatory oestrogen secretion was less than 120 h. None of the females conceived when treated regularly at intervals of 120 h during exposure to fertile males. Discontinuation of treatment resulted in the occurrence of normal implantations in rats that mated 48 h or later after the last dose of centchroman, since in these animals the interval between anti-oestrogen treatment and nidatory oestrogen secretion was greater than 120 h. These findings suggest that the duration of the anti-implantation action of a single oral antifertility dose of centchroman in rats is about 120 h. Recovery of normal blastocysts from rats treated continuously with this dose of centchroman at these intervals suggests lack of significant effect on follicular maturation, ovulation, fertilization, preimplantation development or mating behaviour. Tamoxifen appears to be slightly longer acting and the duration of its action was about 144 h.
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Summary.
The presence of a foreign body in the uterine horn prevented implantation in rats when the process was delayed experimentally for 6 days. The contralateral horn, however, showed normal implantations.
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Summary.
A single local injection of ferrous sulphate or ferric chloride causes total destruction of the testis of adult rhesus monkeys. Histochemically, the injected iron is found to be localized in the tunica propria of the tubules and in the interstitium; it accumulates in the mitochondrial and the supernatant fractions almost in equal amounts. It seems that iron causes a generalized damage to the testis through properties common to other heavy metallic ions.
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Summary.
Antispermatogenic effect of Methallibure (ICI 33828), Tretamine (triethylenemelamine) and Busulphan (1,4-dimethanesulphonoxybutane) was investigated in rhesus monkeys. Methallibure (16 mg/kg for 15 days, orally) had no effect on spermatogenesis, Leydig cells or pituitary gonadotrophic activity. Tretamine (0·05 mg/kg for 30 days, intravenous injection) selectively arrested spermatogenesis at the spermatogonial stage and caused a slight reduction in serum gonadotrophin level. Busulphan (10 mg/kg, single intraperitoneal injection) also suppressed spermatogenesis at the spermatogonial stage but not selectively, since an adverse effect on the interstitium and the accessory genital organs was noted; some reduction in serum gonadotrophin content was also observed. These effects appeared to be reversible. The possible significance of these findings in relation to the modus operandi of these compounds is discussed.
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Summary.
An intra-uterine suture did not evoke any acute changes in the rat uterus. However, prolonged presence of the suture provoked keratinized metaplasia of the epithelium in 20% of the animals and cystic glandular hyperplasia in 10%. The O2 uptake rate was doubled in the treated horn but other biochemical constituents did not undergo any noteworthy change. Pregnancy was invariably prevented in the treated horn. However, this effect was reversed by removal of the suture provided there were no gross abnormalities in the uterus. Animals fitted with the suture before puberty also conceived only in the control horn when their fertility was tested during adult life. The removal of the suture led to pregnancy in both horns. This indicated that the reproductive potential of these animals was not disturbed due to the insertion of the suture during prepuberal life.
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Summary. RU-38486 or ZK-98734 treatment (3 mg/day, s.c.) to intact or hysterectomized adult female rats on Days 5–7 post coitum induced changes characteristic of luteolysis. Ultrastructurally, the luteal cells exhibited an extensive vacuolization of the cytoplasm and perinuclear areas, degeneration of mitochondrial cristae, massive accumulation of lipid droplets, increase in number of lysosome like granules and heterochromatinization of the nucleus. In general, RU-38486 induced more marked degeneration of the luteal cells than did ZK-98734. There was also a significant decrease in peripheral plasma progesterone concentrations in treated rats. We suggest that these antiprogestagens act via inhibition of luteal function in addition to their antagonism at the uterine progesterone receptor level.
Keywords: antiprogestagens; ultrastructure; corpora lutea; progesterone; rat
