Centchroman was administered to rats in relation to luteal phase nidatory estrogen secreted between 21.00 on day 4 and 10.00 on day 5 of pregnancy. A single oral dose of 1.25 mg/kg before the secretion of nidatory estrogen, i.e. until 21.00 on day 4, prevented implantation in 100% of the rats without altering plasma estradiol or progesterone concentration. Administration of a dose of up to 62.5 mg/kg at 10.00 on day 5 even failed to inhibit implantation, but caused dose-dependent resorption of implantations. Resorption of all implantations at a dose of 62.5 mg/kg was associated with a decrease in circulating progesterone levels, but was only partially reversed by progesterone or progesterone + estrone supplementation. Apparently normal morulae and blastocysts recovered between days 4 and 10 from rats treated with anti-implantation doses before release of nidatory estrogen, when transferred to the uteri of control rats exhibited lower pregnancy, implantation and development rates with increasing confinement in the genital tract of treated donors. None of the embryos recovered from control or centchroman treated females implanted in the uteri of treated rats. Centchroman administration on day 1, but not on day 5, abolished endometrial receptivity to an artificial stimulus for decidualization. All term fetuses were apparently normal and their weight comparable to that of control fetuses. The study provides evidence of post-implantation fetal resorption, occurring primarily between days 10 and 19 post-coitum, in rats treated with a potent antiestrogen before or immediately after the prenidatory estrogen secretion. This was not related to altered ovarian function and the decreased plasma progesterone concentration on day 19 after a higher dose of the compound was secondary to resorption of all implantations.

Of the 7 carotane sesquiterpenes of Ferula jaeschkeana Vatke evaluated, three jaeschkeanadiol esters (compounds 3, 5, and 6) showed contraceptive efficacy when administered orally on days 1-7 post coitum in rats. In ovarieetomized immature female rats, however, the active compounds exhibited estrogenie activity and were devoid of antiestrogenie activity. Using a competitive protein binding assay, the compounds 3, 5, and 6 showed relative binding affinity of 0.01%, 5.75%, and 0.75% of 173-estradiol, respectively, for rat uterine cytosol estrogen receptors.

Centchroman [dl-3,4-trans-2,2-dimethyl-3-phenyl-4-[p-(beta-pyrrolidinoethoxy)phenyl] - 7-methoxychroman hydrochloride], an antifertility agent under clinical evaluation, has been resolved into its optical enantiomers. The cytosol estrogen receptor binding affinity and estrogenic, antiestrogenic and antiimplantation activities of the two enantiomers have been determined. The enantiomers display a 7-fold difference in receptor affinity, and a corresponding difference in stimulation of the uterine growth and antiimplantation activity was observed in rats.

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. It has been reported that iron salts cause damage to the gonads of rats and guinea-pigs (Telkka, Kuusisto & Antila, 1956;Kamboj & Kar, 1964). The present report is concerned with the effect of these salts on the testis of rhesus monkeys.Adult male rhesus monkeys {Macaca mulatta) of the Institute's primate colony (8-5 to 9-5 kg) were used in this study. The iron salts (ferrous sulphate and ferric chloride 0-08 m-mole/kg body weight/testis, in 3 ml sterile distilled water; a single injection) were injected directly into the testes under aseptic conditions. The control animal received sterile distilled water alone in a similar manner. For histochemical demonstration of iron (Fe++ and Fe+++) paraffin sections of the testis fixed in 10% neutral formalin were processed according to the procedure given by Pearse (1954). The total cholesterol concentration of the testis was determined by a method employed in a previous study (Kar, Harishchandra & Das, 1963). For subcellular fractionation, the testis samples were homogenized in 0-15 m sucrose and the fractions were isolated by the procedure of Jones & Gutfruend ( 1961 ) using a Servali superspeed refrigerated centrifuge. Iron (as Fe+++) was then estimated from the subcellular fractions by polarographic method using an American Optical 103000 Electropolarizer.It will be evident from the results presented in Table 1 that 7 days after the administration of the salts only the absolute weight of the testis was reduced. However, after 210 days the testicular weight diminished both on absolute and relative basis. Macroscopically, the organ showed necrotic patches at 7 days but at the chronic stage it was only a small mass of yellow coloured tissue. The cholesterol concentration of the testis increased considerably at 7 days but declined relatively at 210 days. The percentage of water showed a substantial decrease only at the chronic stage (Table 1). 115

No abstract