Novel male mice disrupt pregnancy despite removal of vesicular-coagulating and preputial glands.

Exposure to novel males can disrupt intrauterine implantation of fertilized ova in inseminated female mice, an effect established to involve androgen-dependent male excretions. These experiments were designed to examine potential roles of vesicular and coagulating glands, independently or in conjunction with preputial glands. Inseminated females were randomly assigned to conditions of housing below (1) no males; (2) males with vesicular-coagulating gland removal; (3) males with preputial, vesicular, and coagulating gland removal; or (4) males subjected to sham surgery. Males with accessory glands removed disrupted pregnancy to the same extent as did sham-operated males. Long-term testosterone replacement permitted pregnancy disruption in castrated males with vesicular-coagulating and preputial glands removed. Fertility was not disrupted by preputialectomy, but half of the males without vesicular-coagulating glands could not inseminate females. We suggest that males' capacity to disrupt pregnancy could derive from androgen metabolism that is independent of actions on major accessory glands.

Pheromones and novel male-induced pregnancy disruptions in mice: exposure to conspecifics is necessary for urine alone to induce an effect.

Previous research indicates a role of pheromones in novel male-induced early pregnancy disruptions. Although some reports suggest that urine alone is sufficient to produce this effect, others raise procedural concerns and fail to replicate such effects. On Days 1 to 5 after insemination, female CF-1 mice had their nasal regions repeatedly painted with water, urine from males housed in isolation, or urine from males housed in proximity to females. Almost all (87.5%) of the control females delivered litters. There was a small nonsignificant reduction in proportion parturient (78.5%) among females exposed to urine of males housed without social contact. The proportion of females parturient (57.1%) after treatment with urine from males housed in proximity to females was significantly different from controls. The magnitude of the effect of socially stimulated male urine is substantially less than that recorded when males are housed directly above inseminated females separated by a wire-mesh grid. These data suggest that production of pregnancy-disrupting male pheromones is stimulated by contact with conspecifics.

Disruption of early pregnancy by direct and indirect exposure to novel males in mice: comparison of influences of preputialectomized and intact males.

Inseminated female CF-1 mice (Mus musculus) were exposed on days 1 to 5 of pregnancy to unfamiliar outbred males. In the first experiment, inseminated females were each housed directly with the sire, a preputialectomized male, or an intact male. Both types of novel male attempted to mate with the female during this period, unlike the sire. Reinsemination occurred in a significant proportion of the females that were exposed to novel males; this effect was equivalent for preputialectomized and intact males. In two subsequent experiments, we refined a paradigm of indirect exposure to novel males through a wire-mesh grid, which prevents mating and reinsemination. Two or three males housed directly above each female through a grid disrupt pregnancy in most cases, but housing the males below the females is much less likely to do so. In a final experiment, each inseminated female was housed below two males that were either preputialectomized or sham-preputialectomized. Whereas 29 of 33 undisturbed controls were parturient, only eight of 32 females exposed to sham-preputialectomized males and six of 32 exposed to preputialectomized males were parturient. These results suggest that nonvolatile pheromones are involved in novel-male-induced pregnancy disruptions, but that preputial gland emissions are not necessary for such disruptions.

Strange-male-induced pregnancy disruption in mice: reduction of vulnerability by 17 beta-estradiol antibodies.

It is well-established that novel males can disrupt early pregnancy in house mice. Inseminated female C57BL mice were either left undisturbed or each exposed indirectly to a novel HS male through a wire-mesh grid during days 1-6 of pregnancy. Varied dosages of antibodies to 17 beta-estradiol were administered to females exposed to males. Vehicle-treated females exposed to novel males showed fewer litters than did nonexposed controls. Male-exposed females given 1 ml daily of the antibody showed rates of pregnancy comparable to those observed in controls. These data suggest that estrogen levels might play a role in strange-male-induced pregnancy disruptions, converging with evidence implicating estrogens in stress-induced pregnancy blocks.

Strange-male-induced pregnancy disruption in mice: potentiation by administration of 17 beta-estradiol to castrated males.

Previous evidence suggests that androgen activity is necessary for strange males to disrupt early pregnancy in mice. Inseminated females were housed below castrated males, separated by a wire-mesh grid. Castrated males did not disrupt pregnancy, whereas those given daily injections of 27 or 81 micrograms of 17 beta-estradiol did so. In conjunction with previous evidence, these data suggest a similarity between the hormones involved in the capacity of males to disrupt pregnancy and the hormones directly implicated in the females' vulnerability to pregnancy disruption.

Comparison of the adverse effects of adrenal and ovarian steroids on early pregnancy in mice.

In one experiment, female C57- and HS-stain mice were inseminated according to standard procedures and randomly assigned to conditions involving administration of various adrenal and ovarian steroids in the first trimester of pregnancy. The pattern of effects was similar in the two strains, although generally C57 females produced fewer and smaller litters than did HS females. Oestradiol benzoate injections completely blocked pregnancy at doses far less than those effective for other steroids. Corticosterone injections did not produce any significant pregnancy block. Androstenedione injections produced a pregnancy block at 500 micrograms per day. Dehydroepiandrosterone produced a mild pregnancy block at both 500 micrograms and 100 micrograms per day. In a second experiment, the dose-response curve for oestradiol was examined. Daily doses of 0.333 microgram and greater completely blocked pregnancy, a dose of 0.111 microgram did so in the majority of females, and smaller doses had little effect. These results, taken together with other data, suggest that oestrogenic action may mediate the stress-induced block of pregnancy.

Reversal of stress-induced pregnancy blocks in mice by progesterone and metyrapone.

It is established that diverse psychological stressors administered in the first trimester of pregnancy can cause the pregnancy to fail. The physiological mediators of this phenomenon are unknown. In Experiment 1, two strains of female mice were inseminated and randomly assigned to either first trimester physical restraint, restraint plus progesterone, or control conditions. Restrained females produced fewer pregnancies than did controls, and a reversal of this block through the daily administration of 500 micrograms progesterone was seen in HS but not C57 mice. Experiment 2 demonstrated that exposure to a predator will also block pregnancy in the first trimester in C57 mice, and that this can also be counteracted with progesterone administration. Experiment 3 showed that metyrapone, a drug which blocks the conversion of progesterone to corticosterone, also partially reverses a restraint-induced pregnancy block. These results suggest that lowered progesterone levels may be involved in pregnancy blocks induced by psychological stress.

Partial mediation of strange-male-induced pregnancy blocks by sexual activity in mice (Mus musculus).

Novel male house mice (Mus musculus) can disrupt early pregnancy in females. Previous research focused on pheromonal rather than behavioral mediation of this phenomenon. In Experiment 1, novel males were housed with females shortly after insemination. Litter production was negatively correlated with the males' sexual activity. Experiment 2 replicated this finding with a larger sample. In Experiment 3, females were exposed to castrated males. Testosterone-treated males completely blocked pregnancy, whereas untreated males did not. In Experiment 4, castrated testosterone-treated males were presented at intervals after insemination. Pregnancy was totally blocked at Days 3 and 4 and mostly blocked at Days 1 and 2 but was less affected at Days 5 and 6. In Experiment 5, females were exposed through a wire-mesh grid to castrated males. Pregnancies occurred in all conditions, even with testosterone-treated males. These data suggest a role for sexual activity in male-induced pregnancy blocks.

Effect of predator exposure upon early pregnancy in mice.

Female CD-1 and C57 mice were inseminated according to standard procedures and randomly assigned to varied treatments in the first trimester of pregnancy. In the first experiment, mice housed for one week with preselected nonassaultive rats produced very few litters in contrast to controls. In the second experiment, this same effect was observed when inseminated mice were separated from the rat by a wire grid. In the third experiment, inseminated mice were exposed daily to saline or the urine of male or female rats in their home cage bedding. Fewer females exposed to rat urine of either sex produced litters.

Alteration of estrogen-induced lordosis through central administration of corticosterone in adrenalectomized-ovariectomized rats.

Corticosterone was administered through various modes into several brain regions of estrogen-treated adrenalectomized-ovariectomized female rats. Daily administration of 20 micrograms corticosterone dissolved in propylene glycol through intracerebral cannulae effectively inhibited female sexual receptivity at each of four sites: third ventricle, ventro-medial hypothalamus, preoptic area, and septum. Similar administration of lesser daily doses failed to inhibit receptivity. Implantation of pure crystalline corticosterone also had no effect on receptivity at any site. Beeswax pellets chronically releasing low doses of corticosterone significantly inhibited receptivity when implanted in the medial hypothalamus and preoptic area, with similar nonsignificant trends in the lateral septum and medial forebrain bundle, but had no effect in the dorsal hippocampus or the amygdala. The effective sites are similar to those in which estrogen activity is known to induce receptivity and those in which serotonergic activity is believed to inhibit receptivity, but do not entirely correspond to sites in the brain showing the greatest uptake of corticosterone.

Differential sexual activity of isolated and grouped male mice despite testosterone administration.

In Experiment 1, adult male C57 mice were castrated, housed individually or in groups of four, and repeatedly injected with either of two doses of testosterone. Control mice were sham-castrated, individually or group housed, and injected with oil vehicle. In repeated tests of sexual behavior with receptive females, isolated males in all surgery-dose combinations showed significantly more mounts and intromissions than did their group-housed counterparts. Ejaculations were fully restored by testosterone in castrated grouped males but not in castrated isolated males. In Experiment 2, administration of either of two doses of testosterone failed to elevate the sexual behavior of intact group-housed males. These experiments show that housing with other males depresses all major measures of sexual behavior, and suggest that this is probably independent of testicular hormones.

Repeated failure of prenatal ACTH administration to alter masculine behavior in mice.

In four experiments, different preparations and modes of prenatal administration of ACTH all failed to produce any substantial effects upon male sexual behavior in mice. In Experiment 1, CD-1 females implanted during the third trimester of pregnancy with osmotic pumps releasing varied dosages of ACTH1-24 produced male offspring with essentially normal copulatory behavior. In Experiment 2, prenatal injections of high doses of ACTH1-24 had no effect upon male sexual activity. In Experiment 3, osmotic pumps releasing ACTH1-39 during the third trimester of pregnancy had no effect upon sexual behavior of offspring. However, aggressive behavior was significantly reduced, relative to untreated controls, in offspring of all females implanted with pumps, including those releasing only saline. In Experiment 4, third-trimester injections of ACTH1-39 in long-acting gel form had no effect on the sexual behavior or aggression of offspring of C57 strain females. In most of these experiments, ACTH treatment significantly reduced body weight. These results do not confirm previous suggestions that pituitary-adrenal hormones influence the perinatal differentiation of sexually dimorphic behavior.

Facilitation of sexual receptivity in female mice through blockade of adrenal 11 beta-hydroxylase.

Ovariectomized mice were given replacement estrogen and progesterone, and tested for sexual receptivity in the presence of mounting males after various pharmacological manipulations of adrenocortical hormone activity. In Experiment I, females received a chronic regimen of varied dosages of metyrapone, which blocks adrenal conversion of desoxycorticosterone to corticosterone. In each of three repeated measures, females given an intermediate dosage (800 micrograms/animal/injection) showed substantially higher levels of receptivity than those given vehicle injections or other dosages. In Experiment 2, corticosterone administration reversed the facilitatory action of metyrapone on receptivity. In Experiment 3, chronic administration of either desoxycorticosterone or progesterone failed to elevate receptivity. These findings suggest that corticosterone titer may play a role in modulating female receptivity in sexually inexperienced mice.

Suppression of the lordosis reflex in female rats by chronic central melatonin implants.

Pellets with beeswax:melatonin concentrations of 1:0, 5:1, and 2:1 were implanted near the suprachiasmatic nucleus of ovariectomized female rats. In repeated standard measures of the lordosis reflex after estrogen replacement, females with pellets containing either melatonin concentration were consistently less sexually receptive than were females with pure beeswax implants. Suppression of behavioral receptivity by melatonin is consistent with other antireproductive effects of the hormone. Melatonergic action could account for certain pharmacological findings previously attributed to serotonergic action.

Suicidal ideation and the residual capacity to promote inclusive fitness: a survey.

It has been argued that suicide relates to a diminished residual capacity to promote inclusive fitness, defined as the welfare and reproduction of self and kin. The present study examined whether this relationship is reflected in suicidal and subsuicidal ideation in the general population. A questionnaire concerning parameters of inclusive fitness, suicidal ideation and experience, and attitudes toward the value of life was distributed to samples of the general public and university undergraduates. Analyses indicated significant moderate relationships between inclusive fitness and suicidal ideation in both samples. Among items most strongly related to reported suicidal ideation were expectations of poor future health, perceptions of being burdensome, and unstable heterosexual relationships, with importance of other factors depending on age.

Dominance in intermale encounters and subsequent sexual success in mice.

In Experiment 1, when previously isolated male mice were paired and given a female, they fought before beginning to mount, and the more aggressive male ejaculated somewhat more frequently. Males housed together for several days showed little aggression when jointly given a female, but those that were more aggressive in the home cage clearly ejaculated more frequently. In Experiment 2, males were paired for 4 days after a period of isolation. More aggressive males showed more ejaculations when subsequently tested individually with females, but not when pair members conjointly encountered females. In Experiment 3, males were paired for several weeks before encountering females. In cases in which home cage dominance was constant, the more aggressive males ejaculated more frequently both when tested individually and when tested as pairs.

Facilitation of estrogen-induced receptivity through metyrapone administration in ovariectomized rats.

Previously it has been established that adrenalectomy facilitates lordosis in estrogen-primed ovariectomized female rats and that corticosterone administration restores lordosis to preadrenalectomy levels. The present study examined the effects of an inhibitor of the synthesis of corticosterone, metyrapone, upon lordosis in ovariectomized females. In Experiment 1, chronic administration of moderate doses of metyrapone was found to facilitate lordosis. In Experiment 2, a single metyrapone administration at various doses and time intervals before testing had a mild facilitatory effect on lordosis. Experiment 3 compared the effects of metyrapone on ovariectomized and adrenalectomized-ovariectomized females. The absence of a facilitatory effect in adrenalectomized females suggests that the drug's effect on lordosis is mediated by its established inhibitory effects on 11 beta-hydroxylation in the adrenal. These data are consistent with indications that corticosterone titer modulates female receptivity.