In utero proximity of female mouse fetuses to males: effect on reproductive performance during later life.
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Biomedical subjects
Publications and source records attributed to F H Bronson.
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Serum levels of FSH in ovariectomized female mice are only partially suppressed by estradiol regardless of the dosage administered. Conversely, within the limits of detection, serum FSH in intact females is totally suppressed by estradiol. Thus, the present experiments used the maximally estrogenized, ovariectomized female as a test system for evaluating other nonestrogenic factors which could depress serum FSH. It was found that a transplanted ovary lowered serum FSH dramatically under such conditions. Of the large number of steroid and pituitary hormones tested, however, only large doses of testosterone propionate yielded any further suppression of serum FSH (24%). Charcoal-extracted follicular fluid (porcine) markedly lowered serum FSH concentrations (50% suppression), while a charcoal-extracted saline homogenate of PMS-treated mouse ovaries also was active in this regard (26% suppression). Finally, charcoal-extracted porcine follicular fluid was administered to nonestrogenized, ovariectomized females, where it both depressed serum FSH and markedly elevated serum LH concentrations. These studies, when viewed in toto, support a contention that follicular fluid contains a nonsteroidal factor which is capable of acting additively with estradiol to regulate FSH secretion. The question of whether this factor also regulates LH secretion in a reciprocal fashion in the mouse requires further work.
This study tested the hypothesis that subordination in male mice is directly related to reduced levels of circulating testosterone. Several measures of aggressiveness and submissiveness were quantified during or after daily encounters between pairs of intact males, castrated males, or castrated males bearing testosterone implants that were designed to maintain plasma testosterone titers at levels slightly above those of intact males. Behavioral measures included the total amount of fighting that resulted from daily pairing, the tendency for subordinates to fight back, and the relative frequency of urine marking. In all these regards, pairs of testosterone-implanted, castrated males formed dominant-subordinate relationships that involved apparently normal submissive behavior (compared to intact control pairs). Thus we found no evidence that submissive behavior was directly related to a reduction in circulating testosterone titers.
Circulating pituitary gonadotropins and testicular function were examined in aged CBF1 male mice using two experimental designs: a) a longitudinal analysis of 2 to 30-month-old males, and b) a direct comparison of weight-matched, sexually-active vs. sexually-inactive 24-month-old males, all of whom were relatively robust. Measurements included serum concentrations of testosterone, follicle stimulating hormone, and luteinizing hormone, gonadotropic responsiveness to castration, success in a 4-day mating test, testicular sperm content, and reproductive organ weights. The longitudinal analysis showed progressive losses in mating success and sperm production between 18 and 30 months, changes which were correlated with decreased levels of serum LH and testosterone but not with FSH. The direct comparison of robust, sexually-active vs.-inactive males provided a better design for identifying reproductive-specific effects of aging, as opposed to debilitative changes that are general to several supporting systems. Such comparisons in 24-month-old CBF1 males suggest the existence of a subpopulation of mice in which reproductive failure is specifically correlated with a loss in the episodic release of LH.
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Puberty may be induced rapidly in young female mice by exposing them to adult males. The relevant male stimuli include a urinary pheromone and tactile cues, the latter acting in a potentiating capacity. The specific action of the urinary pheromone on pituitary gonadotropins was the subject of the present research. Immature females of a standard size were either paired with adult males, isolated and their bedding sprayed with male urine, or maintained as isolated controls. Exposure to male urine resulted in a rapid and significant release of LH (30 min) which was maintained at an average of 50% higher than levels in isolated controls throughout the 48 h experiment; no immediate changes were observed in either serum FSH or prolactin, but FSH was depressed and prolactin rose progressively during later sampling periods. Cohabitation with an adult male yielded parallel but decidedly stronger reponses in the concentrations of all three hormones. Exogenous estrogen, administered in a second experiment at a dosage previously found to mimic the puberty-inducing action of a male, suppressed serum FSH and LH while elevating serum prolactin. Thus, the present results suggest a) that the male's urinary stimulus exerts its action on immature females via LH release with no immediate and/or direct effects on the other two tropic hormones, and b) that the delayed alterations in serum FSH and prolactin concentrations accompanying male- and/or urine-exposure are secondary consequences of an LH-induced release of estradiol. Attempts to induce the entire pubertal cycle in intact females with subovulating doses of LH, nevertheless, were unsuccessful.
Five experiments consistently demonstrated the existence of a factor(s) in the urine of female mice which stimulates gonadotropin secretion in male mice. The factor, presumably a priming pheromone, is not found in the urine of intact or castrated males nor is it in the urine of female hamsters. Furthermore, the potency of female mouse urine is apparently independent of ovarian state. In the response of the male, the release of LH is more dramatic than that of Fsh. as little as 10 min of exposure to female urine produced significantly elevated LH levels at 30 min. Finally, the male's responsiveness is largely, and possibly entirely, independent of his sexual experience. These results are discussed within the framework of a two-way pheromonal system by way of which urinary factors of both sexes modulate gonadotropin and gonadal hormone secretion in the opposite sex.
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Previous work has shown that exposure of prepubertal female mice to an adult male results in an immediate, sequential release of LH and estrogen. An ovulating release of LH follows in a predictable 3-day period, providing that male-exposure occurs at a particular body weight. Using this three day system, the present objective was to determine how effectively exogenous estrogen would substitute for the male's presence. Control experiments established that neither social isolation nor exposure to a castrated male would yield ovulatory puberty within the 3-day experimental period. Immature females were then subjected to a variety of sequences of three daily treatments including male-exposure and/or steroid injection. Two days of male exposure and no treatment on the third day was as effective in eliciting ovulation on the third night as 3 full days of cohabitation. Furthermore, either or both of the first two days of male-exposure could be mimicked by single injections of estrogen if followed by male-exposure for the remainder of the experimental period. A single injection of estrogen on the first day was ineffective in eliciting ovulation unless followed by male-exposure for 2 days, by a second injection of estrogen on day 2, or by an injection of progesterone on the third day. It was concluded that, as far as the induction of puberty is concerned, the important action of the male's presence is to elicit estrogen secretion (via a subovulating release of LH), and that this process must continue for 2 days, even in immediately prepubertal females, if the pubertal ovulation is to occur during the third night.
Urine marking was examined in house mice, deermice, gerbils and hamsters. The frequency of urine deposition varied with the species, and a correlation is suggested between the propensity of males to mark in this fashion and prepuce length and morphology. We postulate an adaptational advantage for a long penis sheath and for a particular configuration of the prepuce; i.e. to act as a wick for the deposition of urinary pheromones.
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