Reserpine: inhibition of olfactory blockage of pregnancy in mice.

Failure of pregnancy in newly mated female mice exposed to fresh urine from alien males is prevented by administration of reserpine, at 6.25 micrograms per day per female, on days 1 to 5 post coitum-that is, throughout the period of exposure to male urine and for 2 more days. Since reserpine is known to suppress the inhibitory center in the hypothalamus controlling the release of prolactin, inhibition by reserpine of the blockage of pregnancy provides a strong direct indication of hypothalamic mediation in the male-induced failure of pregnancy in mice.

Functional significance of the cells in the pars anterior of the pituitary gland of the musk shrew (Suncus murinus L.).

Seven morphologically and tinctorially distinct types of cells (types 1--7) have been distinguished in the pars anterior of the pituitary gland of the musk shrew (Suncus murinus L.). On the basis of their responses to various experimental stimuli, these cell types were correlated with the secretion of various trophic hormones. Type 1 cells exhibited conspicuous changes after thyroidectomy or inactivation of the thyroid gland and hence appeared to be the source of TSH. Types 2 and 3 cells responded to gonadectomy and administration of androgens, which suggests that they were associated with gonadotrophin secretion. The granules of the type 2, but not the type 3 cells could be extracted with 10% trichloroacetic acid, which may indicate that type 2 and 3 cells secrete FSH and LH respectively. After the administration of either reserpine or oestrogen, the type 4 cells underwent hypertrophy and hyperplasia, which suggests that they were the likely source of prolactin. Type 6 cells, which are distinguishable from type 4 cells by their thinly dispersed erythrosinophilic granulation, showed conspicuous changes after unilateral adrenalectomy, administration of metyrapone or exposure to stress and may therefore be responsible for secretion of ACTH. Type 5 cells tinctorially resembled the somatotrophic cells of other mammalian species and did not respond to any of the experimental treatments used in the present study. It is therefore possible that these cells have a somatotrophic function. The possible significance of type 7 cells has been discussed previously.

Male-induced implantation failure (the Bruce effect) in mice: protective effect of familiar males on implantation.

Housing newly inseminated female mice in contact with a familiar male (a male that had cohabited with the female for 24 h during the pericopulatory period, but not the coital partner) depressed the implantation failure (the Bruce effect) induced by exposure to alien males. This is comparable to the protective effect of stud males on implantation in alien male-exposed females. The findings imply that exposure to a male (stud or any other) during the pericopulatory period enables the female to memorize the male-originating olfactory cues, and that this memory formation is not contingent upon mating. Reexposure to the male-originating olfactory cues induces a luteotrophic effect in the newly inseminated female, which accounts for the protective effect of the stud/familiar male on implantation in the alien male-exposed female. The male-originating olfactory cues that provide the protective effect on implantation act through contact. The findings also lend support to the view that the female mouse is capable of identifying a male as an individual through olfactory cues perceived during the pericopulatory period.

Induction of pseudopregnancy in pregnancy-blocked mice by re-exposure to stud males.

Re-exposure to stud males beginning on day 4 post coitum induced pseudopregnancy in a large proportion of female mice whose pregnancies were terminated by a single injection of 0.5 mg of bromocriptine on day 1 post coitum. By contrast, exposure to alien or strange males was ineffective in inducing pseudopregnancy in pregnancy-blocked females. The results suggest that the newly inseminated female retains the memory of the stud male for some days after mating. Activation of the 'memory' by pheromones of the stud males exerts a luteotrophic effect in pregnancy-blocked females resulting in the incidence of pseudopregnancy. This may account for the inability of the stud male to block pregnancy in his coital partner and also for the inability of alien males to block implantation in newly inseminated females housed with stud males.

Effect of bilateral transection of the lateral olfactory tract on the male-induced implantation failure (the Bruce effect) in mice.

Bilateral transection of the lateral olfactory tract (LOT) at the rostral level induced anosmia in female mice; by contrast, sectioning of the LOT at more caudal levels failed to induce anosmia in females. Transection of the LOT at all the levels inhibited the alien male-induced implantation failure in newly inseminated mice (the Bruce effect). Sham-operated as well as intact females exhibited a high rate of implantation failure following alien male exposure. The results suggest that the inhibition of the Bruce effect in LOT-transected females is not due to anosmia induced by the operation procedure, but due to interruption of the primary olfactory bulb projections to the posterior parts of the olfactory cortex. Our results rule out the involvement of the nervus terminalis in the Bruce effect. The present report lends support to the involvement of the accessory olfactory system in the transmission of the pheromonal stimulus involved in the male-induced implantation failure.

Testicular toxicity of WIN 18446 in the laboratory mouse.

The effect of oral administration of N,N'=bis (dichloroacetyl)-1, 8-octamethylenediamine (WIN 18446) (200 mg/kg body weight/day, up to 30 days) on the testis of the Parkes (P) strain laboratory mouse was studied. The drug caused reduction in testicular weight and severe atrophic changes in the seminiferous tubules. A duration-dependent effect of the drug was observed on the germ cells. The drug had its initial impact on spermatids followed by spermatocytes, ultimately culminating in the Sertoli cell-spermatogonia syndrome. The drug-induced changes included exfoliation of germ cells, formation of multinucleated giant cells, and vacuolization of cytoplasm and displacement (towards the lumina of the tubules) of Sertoli cell nuclei. Even 75 days after drug withdrawal, testicular weight remained depressed and in 15 to 20% of the tubules there was incomplete recovery of spermatogenesis. Our data indicate that WIN 18446 induces sustained impairment of spermatogenesis by a direct action on spermatogonia or indirectly by affecting the integrity of the Sertoli cells. The Leydig cells remained unaffected in WIN 18446-treated mice.

Protective effect of ectopic pituitary graft on nutritional stress-induced implantation failure in mice.

Implantation failure in newly inseminated mice induced by food deprivation was prevented by the presence of an ectopic pituitary graft. Since a pituitary graft in an ectopic site is known to secrete prolactin continuously, it is suggested that suppression of implantation failure in pituitary-grafted females is due to the luteotrophic support provided by the graft. The results provide supportive evidence for the view that depression of hypophysial prolactin is the primary endocrine cause of the nutritional stress-induced implantation failure in mice.

Stud male-induced protection of implantation in food-deprived mice: masking effect of an artificial scent on pheromonal odour.

In contrast to unscented stud males, stud males anointed with a commercial perfume failed to protect implantation in food-deprived females. It is suggested that the failure of perfumed stud males to protect pregnancy in their coital partners is due to the masking effect of the perfume on the stud male-originating olfactory cue which stimulates luteotrophic activity in females. The results are also consistent with the view that the newly inseminated female mouse identifies the stud male as an individual through a pheromonal cue and this is involved in the protective effect on implantation in the food-deprived female.

Failure of familiar males to prevent alien male-induced implantation block (the Bruce effect) in laboratory mice.

Implantation failure in newly inseminated females induced by exposure to alien males (the Bruce effect) was significantly reduced when the females were housed with the stud male. By contrast, newly inseminated females housed with a familiar male during exposure to alien males exhibited a high rate of implantation failure. The results suggest that the protective effect of the stud male on implantation is not because of the familiarity of the female with his odour cues. The results are consistent with the view that the newly inseminated female mouse identifies her coital partner as an individual because she becomes 'imprinted' with his odour during the pericopulatory period.

Bromocriptine-induced implantation failure in mice: failure of the stud male to protect pregnancy.

The presence of the stud male failed to prevent implantation failure in newly inseminated females induced by administration of bromocriptine. This is in contrast with the ability of the stud male to prevent implantation failure in females induced by alien male exposure, and nutritional stress. Since bromocriptine is a potent inhibitor of hypophysial prolactin release by virtue of its stimulatory effect on hypothalamic dopaminergic activity, the results suggest that the stud male-originating luteotrophic stimulus is incapable of overriding the dopaminergic activity in bromocriptine-treated females.

Rat-induced disruption of early pregnancy in mice and its prevention by the stud male.

Recently inseminated mice exhibited a high rate of pregnancy failure following exposure to male rats irrespective of whether they were housed in direct physical contact with the rat or not. Pregnancy disruption was also seen in mice which were housed on male rat-soiled bedding. By contrast, inseminated mice housed with female rats or on bedding soiled by female rats showed a significantly lower rate of pregnancy failure. The presence of the stud male prevented the pregnancy failure in mice induced by exposure to male rats or male rat-soiled bedding. This protective effect of the stud male on pregnancy in rat-exposed mice is analogous to the protective effect of the stud male on pregnancy in conspecific novel male-exposed mice and in mice subjected to nutritional stress. Hence the possibility that the protective effect of the stud male on pregnancy in male rat-exposed mice is due to the stimulation of luteotrophic activity by the stud male-originating olfactory cues cannot be ruled out. However, it is not clear whether the pregnancy failure in newly inseminated mice induced by exposure to rats is the result of a general stress or is mediated through rat-originating chemosignals acting interspecifically.

Nutritional stress-induced implantation failure in laboratory mice: inhibition by continuous illumination.

The implantation failure in newly inseminated mice induced by food deprivation for 48 hr, beginning at 0900 hrs on day 4 post coitum, was prevented by simultaneous exposure to light continuously for 48 or 36 hr. Food-deprived females that were exposed to continuous light for 36 hr showed a significant increase in fetal resorption as compared with food-deprived females exposed to continuous light for 48 hr. Since failure of hypophysial prolactin release appears to be the primary endocrine cause of the inanition-induced implantation failure, the results suggest that exposure to continuous light protects implantation in food-deprived females by stimulating luteotrophic activity.

Failure of deodorized males to induce oestrus in the wild mouse.

The ability of female mice to return to oestrus following exposure to males perfumed either with oil of wintergreen or with the commercial perfume, "Kanta" was evaluated. Unisexual grouping of female mice induced anoestrus in all individuals. Oestrus was, however, promptly induced in the majority of unisexually grouped females by exposure to normal males. By contrast, exposure to perfumed males failed to induce oestrus in unisexually grouped females. The results suggest that male urine which is the source of the primer pheromone involved in the induction of oestrus was ineffective because of the masking effect of artificial scents. Hence the unisexually grouped females were unable to perceive the pheromone from males and continued to remain in anoestrus following exposure to perfumed males. The results provide additional evidence in support of the view that the urinary pheromone produced by males induces oestrus in females by acting through olfactory pathways.

Changes induced by morphine administration in the hypothalmic neurosecretory system of the spotted owlet, Athene brama Temminick.

The effect of chronic administration of morphine, in gradually increasing doses, on the histology of the HNS of the spotted owlet was investigated. Administration of morphine in low doses (0.25-0.75 mg/day), for 9 days, induced marked depletion of NSM from all regions of the HNS, except the zona externa of the AME. Maximum depletion of NSM was noticed in the HNS of birds treated with morphine for 9 days. Beyond the 9th day, the HNS did not exhibit further depletion of its NSM. Administration of morphine in high doses (1.5-4 mg/day), for 18 days, did not cause depletion of NSM from the HNS. On the other hand there was noticeable increase of the NSM in the HNS over that of the controls. The histological changes in the HNS induced by low doses of morphine are comparable to the changes induced by hypertonic saline administration and are presumably indicative of augmented secretion of the ADH. The accumulation of NSM in the HNS of birds receiving high doses of morphine suggests a decrease in neurohypophysial activity. The results therefore indicate that the effect of morphine on the HNS of the spotted owlet is dose-dependent. The mechanism of action of morphine on the neurohypophysis is briefly discussed.

Evidence for the involvement of serotoninergic system in the male-induced ovo-implantation failure (Bruce effect) in mice.

Failure of ovo-implantation in newly mated female mice induced by exposure to alien males (Bruce effect) was prevented by administration of 2-(1-piperazinyl) quinoline maleate (quipazine). Since quipazine has serotonin receptor agonistic effect resulting in the elevation of prolactin secretion, it is suggested that the increased secretion of prolactin induced by the drug prevented the Bruce effect. The results suggest the involvement of the serotoninergic system in the sequence of events that leads to the Bruce effect.