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M. S. SANKARAN and M. R. N. PRASAD

Summary.

The comparative effects of cis- and trans-clomiphene and oestradiol-17β on the sialic acid concentration in the uterus, cervix and vagina were studied in rats during experimentally induced delayed implantation. The cis- or trans-isomer of clomiphene caused a progressive dose-dependent increase in sialic acid in the uterus and cervix whereas vaginal sialic acid decreased with increase in the dose of the respective compounds.

Cis- and trans-clomiphene and oestradiol-17β all caused a sharp increase in the sialic acid content of the uterus, cervix and vagina 6 hr after the administration of the respective compounds. There was a decrease in sialic acid in all the three tissues at subsequent time intervals in cis-clomiphene or oestradiol-treated rats. The oestrogenic effects of trans-clomiphene lasted even up to 48 hr in all three reproductive tract tissues, indicating that trans-clomiphene is more oestrogenic than the cis-isomer. Differences in the response of the uterus, cervix and vagina to administration of the compounds are discussed in relation to their embryological origin.

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M. RAJALAKSHMI and M. R. N. PRASAD

Summary.

Changes in the secretory activity of the epididymis and accessory glands were studied in the rat during the transition from the prepuberal to the puberal state. Administration of ORF 1616 or cyproterone acetate, either alone or in combination, decreased the levels of sialic acid and protein in the caput and cauda epididymidis. The significance of these changes is discussed in relation to the physiology of the epididymis of the puberal rat.

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PUSHPA SETH and M. R. N. PRASAD

Summary.

The five-striped Indian palm squirrel, Funambulus pennanti, is a seasonal breeder from January to August. Mature females are sexually quiescent from September to December; recrudescence of the gonad starts in late December. The palm squirrel is a reflex ovulator. A mature female may produce two litters of approximately three young each in one breeding season. The period of suckling is 6 weeks. Mature females experience a short period of post-lactational anoestrus during the breeding season prior to the onset of second oestrus. The role of exteroceptive factors in regulating the reproductive cycle of the palm squirrel is discussed.

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M. R. N. PRASAD and S. P. KALRA

Summary.

Clomiphene causes failure in implantation of blastocysts when administered to rats before implantation. This may be due either to a direct blastotoxic effect of the chemical or to elimination of blastocysts from the uterus. Further studies were made to elucidate the anti-implantation effect of the chemical. Clomiphene (0·3 mg/kg/day) was administered orally to rats on Day 9, Days 9 and 10, or Days 9, 10 and 11 after mating during experimentally induced delayed implantation. Uterine horns were flushed 24 hr after the last treatment. While 100% of the rats showed an average of four blastocysts/rat in initial controls, there was a marked reduction in the percentage (37·5) of rats showing blastocysts and in the number of blastocysts recovered from uteri of treated rats, depending on the dose and the time interval allowed for action of the compound. Ligation of uterine horns at the cervical end before treatment resulted in recovery of normal numbers of blastocysts in 75% of rats. These results indicate that blastocysts are expelled from non-ligated uteri. Initiation of oestrogen treatment (1μg/day) 6, 24 and 48 hr after first administration of clomiphene failed to cause implantation of blastocysts in ligated uteri. However, normal numbers of implantation sites were seen in the ligated horns of controls. It is, therefore, conceivable that failure of implantation following clomiphene administration may be due : (a) to increased motility of the uterus resulting in expulsion of the blastocysts; (b) to its anti-oestrogenic and/or antihistaminic activity which prevents preimplantation changes in the uterus normally initiated by exogenously administered oestrogen. Our results show that clomiphene has no direct cytolytic effects on the blastocysts.

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A. H. REDDI and M. R. N. PRASAD

Summary.

The reproductive cycle of the male Indian palm squirrel was investigated from a collection of 365 animals during the period May 1963 to May 1965. It breeds from January to the end of July. This is followed by a period of regression (August-September) and the animals are quiescent during October and November. Redevelopment of the reproductive organs is initiated in December and results in the restoration of reproductive activity in late January. Sexual maturity in squirrels is attained by 8 to 9 months of age. The histological changes in the testis, epididymis and vas deferens with age and breeding season are described. The weights of the prostate gland and seminal vesicles show changes that parallel testicular weights and interstitial cell morphology. However, there is a time lag in the response of accessory glands both during the transition from puberal to the adult condition and in adults during the change from recrudescence to breeding condition. The role of exteroceptive factors in regulating the reproductive cycle of the palm squirrel is discussed.

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SURESH MOHLA and M. R. N. PRASAD

In earlier studies which showed that oestrogen activates the synthesis of RNA, DNA and protein in the blastocyst and uterus during delayed implantation, it was postulated that activation of the delayed blastocyst might be due to the direct action of oestrogen (Mohla, 1968; Prasad, Dass & Mohla, 1968; Dass, Mohla & Prasad, 1969).

One of the earliest effects of oestrogen on the rat uterus is the release of adenosine 3′5′-monophosphate (cyclic ApMP), the levels of which are enhanced within 15 sec after the intravenous administration of oestrogen (Szego & Davis, 1967). Griffin & Szego (1968) showed that cyclic ApMP, like oestrogen, enhanced within 5 min the incorporation of labelled amino acids into the protein of uterine segments of untreated ovariectomized rats. They postulated that the cyclic ApMP released as a result of oestrogen treatment also participates in the early effects of oestrogen on the uterus. A further effect,

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S. P. KALRA and M. R. N. PRASAD

Summary.

The effects of long-term administration of clomiphene on immature, intact male rats and their reproductive performance following cessation of treatment are reported. Clomiphene, at a dose of 250 μg/day or higher, inhibited spermatogenesis at the primary spermatocyte stage, the Leydig cells were atrophic and consequently the accessory glands were non-secretory. The testis resumed normal spermatogenesis immediately following withdrawal of treatment and spermatozoa appeared in the seminiferous tubules within 30 days of the period of recovery. The recovered males sired normal young when caged with virgin cycling females. It is suggested that the inhibitory effects on the testes and accessory glands following long-term administration of clomiphene are due to the oestrogenicity of the compound which may modify the synthesis and/or release of the gonadotrophins mediated through the hypothalamo-hypophysial axis.

The results are discussed in relation to the sequence of recovery of the gonads and accessory glands.

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M. R. N. PRASAD, M. SAR and W. E. STUMPF

Summary.

The present studies were undertaken to obtain information about the localization of oestradiol in rat blastocysts and to elucidate the interrelationship between hormone localization and function. Tritiumlabelled oestradiol was administered intraluminally into the uterus or subcutaneously in rats in which implantation was delayed by ovariectomy on Day 3 post coitum followed by treatment with progesterone. Rats were killed 5, 15 and 30 min after intraluminal instillation or 5, 15 and 60 min after subcutaneous injection of [3H]oestradiol. Autoradiograms of flushed-out blastocysts as well as a blastocyst in situ showed no retention and subcellular concentration of radioactivity while, in uterine stromal, glandular and muscle cells, characteristic nuclear concentration and retention of the steroid were observed. Since blastocysts are metabolically activated by treatment with oestradiol, several possible mechanisms are discussed to explain the activation of blastocysts in the apparent absence of oestradiol-binding proteins in cells of the blastocysts.

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M. R. N. PRASAD, C. M. S. DASS and SURESH MOHLA

Summary.

The metabolic changes in the pre-implantation blastocyst have been studied by instillation of 3H-cytidine, 3H-phenyl alanine and 3H-thymidine into the uterine lumen in experimentally induced delayed implantation and at specific time intervals after the administration of oestrogen.

Minimal RNA synthesis occurs in the blastocyst and uterus during delayed implantation. Minimal protein synthesis is seen only in the uterine epithelium during this period. Oestrogen enhances the synthesis of RNA, DNA and protein in the blastocyst while only RNA and protein synthesis are activated in the uterus. The significance of these oestrogeninduced changes in the blastocyst and uterus is discussed in relation to implantation.

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MUHAMMAD ARSLAN, RICHARD C. WOLF, ROLAND K. MEYER and M. R. N. PRASAD

Summary.

Twelve immature female monkeys were treated with varying amounts of pregnant mare's serum gonadotrophin (pmsg). Seven of these monkeys responded to pmsg treatment as shown by sex skin development, ovarian enlargement and withdrawal bleeding. These animals reached menarche between 23 and 26 months of age, almost 1 year earlier than untreated control monkeys. Five other animals did not show an initial response to pmsg treatment and attained puberty simultaneously with the untreated animals. It is suggested that increased production of oestrogen by the pmsg-stimulated ovaries may affect the hypothalamo-hypophysial axis in such a way that puberty is accelerated.