Sexual maturation in female rats: hereditary, developmental and environmental aspects

Two physiological components of sexual maturation, vaginal opening and first estrus, apparently evolve similarly in Wistar and Sprague-Dawley rats. However, a bimodal distribution in the frequency of the days of vaginal opening is observed within a given strain, which is less related to heredity than to the timing and type of experiment. In addition, when the modulators of sexual maturation are reviewed, it can be observed that sensitivity to external stimuli can vary even within a strain. For a defined set of breeding conditions, one group of rats can be more susceptible to changes in the lighting regimen and not be affected by controlled stressors, while another group responds more to stress and less to light. The reason for susceptibility to one rather than another environmental factor under similar breeding conditions is not understood. In that context, it is difficult to evaluate the role of heredity when we cannot understand the full impact of the environment, not to mention maternal influence in fetal and early life. Using two lines of psychogenetically selected rats, it was possible to show that they had differences in sexual maturation, which strongly suggested a genetic predisposition. Nevertheless, the question arises as to whether the genetic locus directly affects organs implicated in sexual maturation or whether it acts on some unknown factor which only secondarily modifies sexual maturation. In summary, there is more need to understand the role of the environment, including that of the mother early in fetal and neonatal life. It is suggested that the mechanisms underlying organ growth are set for a given species, while developmental and environmental factors fix the timing of vaginal opening and first ovulation. In the rat, there appear to be two times which are preferred for vaginal opening, given the laboratory conditions that have been used in the last 20 or so years: an early period, at 31-35 days, and a late period, at 36-40 days. An explanation for this dichotomy would be that a combination of parameters (not necessarily always the same) is needed for vaginal opening. These parameters oscillate during sexual maturation with different frequencies, which can achieve resonance to lead to vaginal opening and ovulation only during given periods.     

Effect of an LH-RH antagonist on reproductive status of immature female rats.

Administration of the LH-RH antagonist, D-Phe2-D-Ala6-LH-RH (Wy-18, 185) to immature female rats from days 25--35 of age was without significant effect on day of vaginal opening (puberal onset), weights of the ovaries, uteri and anterior pituitary, and on ovarian histology on autopsy day 39.     

Effect of an LH-RH antagonist on reproductive status of immature female rats

Summary Administration of the LH-RH antagonist, D-Phe²-D-Ala⁶-LH-RH (Wy-18, 185) to immature female rats from days 25–35 of age was without significant effect on day of vaginal opening (puberal onset), weights of the ovaries, uteri and anterior pituitary, and on ovarian histology on autopsy day 39.The technical expertise of J. Tracy is gratefully acknowleged.     

Bromocryptine treatment and puberty attainment in the female rat

Summary The influence of bromocryptine treatment on the timing of vaginal patency and 1st oestrus in female rats was studied. No significant influence of bromocryptine on these parameters was noted, and it is concluded that suppression of prolactin secretion has no effect on puberty attainment.Acknowledgment. We thank Professor E. Flückiger and Dr H. Friedli, Pharmaceutical Division, Sandoz Ltd, Basle, Switzerland, for the donation of bromocryptine mesylate.     

The age-dependent difference in the response of the vagina to the neonatal administration of testosterone propionate in Long-Evans female rats

Summary The ability of the vaginal epithelium to respond to testosterone propionate by producing keratin was established when female rats were 3 days of age, whereas the vaginal stroma from rats 2 days old or less was capable of responding to the androgen and might destroy the vaginal epithelium.     

Deciduoma formation in rats with cornified vagina.

In female rats given a single injection of 1.25 mg 5 alpha-dihydrotestosterone during neonatal life, reactivity of the vaginal mucosa to hormones was permanently altered, so that the rats, when adult, could show vaginal cornification under the hormonic conditions supportive of development of deciduomata in the uterus.     

Beobachtungen zur Beschleunigung der Geschlechtsreife junger Mäuseweibchen durch die Gegenwart adulter Männchen und durch exogenes Oestrogen

Summary The influence of the presence of adult males on the acceleration of sexual maturation of female mice was examined under various experimental conditions and compared with the influence of exogenous oestrogen. The criteria of sexual maturation were not equally influenced. It is concluded that sexual maturation is a complex feature and that acceleration of single criteria does not signify sexual maturation.     

Effect of glucocorticoids injected into pregnant female mice and rats on weight of male sexual glands in adult offspring and testosterone level in fetus in genotype-dependent

Injection of corticosterone into CBA/Lac, C57BL/6J and BALB/c mice, or hydrocortisone into aggressive and domesticated rats, on days 16 and 18 of pregnancy decreased the weight of sexual glands in adult male offspring of the C57BL/6J and domesticated mothers but increased these values in male offspring of the CBA/Lac and aggressive mothers. When injected into pregnant aggressive and domesticated rats, corticosterone affected testosterone levels in 21-day-old male fetuses. The changes were also genotype-dependent and followed the course of changes in the weight of the accessory sex glands in adults. It is suggested that glucocorticoids given during the prenatal period can effect plasma testosterone levels of male fetuses and the development of the sexual glands in a genotype-dependent manner.     

Pineal melatonin rhythms and the timing of puberty in mammals

The direction of change in daylength provides the seasonal time cue for the timing of puberty in many mammalian species. The pattern of melatonin secretion from the pineal gland transduces the environmental light-dark cycle into a signal influencing the neuroendocrine control of sexual maturation. The change in duration of nocturnal melatonin secretion is probably the key feature of the melatonin signal which conveys daylength information. This information may also be used by neuroendocrine axes controlling seasonal changes in pelage colour, growth and metabolism. The mechanism of action of melatonin on neuroendocrine pathways is unknown. Although the ability to synthesize and secrete melatonin in a pattern that reflects the duration of the night may not occur until the postnatal period, the rodent and ovine foetus has the ability to respond in utero to photoperiodic cues to which its mother is exposed in late gestation. Transplacental passage of maternal melatonin is likely to be the mechanism by which photoperiodic cues reach the foetus. Species which do not exhibit seasonal patterns of puberty, such as the human, also secrete melatonin in a pattern which reflects the environmental light-dark cycle, but they do not respond reproductively to the seasonal melatonin information.     

Pineal melatonin rhythms and the timing of puberty in mammals

Summary The direction of change in daylength provides the seasonal time cue for the timing of puberty in many mammalian species. The pattern of melatonin secretion from the pineal gland transduces the environmental light-dark cycle into a signal influencing the neuroendocrine control of sexual maturation. The change in duration of nocturnal melatonin secretion is probably the key feature of the melatonin signal which conveys daylength information. This information may also be used by neuroendocrine axes controlling seasonal changes in pelage colour, growth and metabolism. The mechanism of action of melatonin on neuroendocrine pathways is unknow. Although the ability to synthesize and secrete melatonin in a pattern that reflects the duration of the night may not occur until the postnatal period, the rodent and ovine foetus has the ability to respond in utero to photoperiodic cues to which its mother is exposed in late gestation. Transplacental passage of maternal melatonin is likely to be the mechanism by which photoperiodic cues reach the foetus. Species which do not exhibit seasonal patterns of puberty, such as the human, also secrete melatonin in a pattern which reflects the environmental light-dark cycle, but they do not respond reproductively to the seasonal melatonin information.     

Placental and fetal contraindications of dexamethasone administration to pregnant rats

Summary Dexamethasone (DEXA) given to pregnant rats for either the last 3 or 6 days of gestation lowered placental, fetal body and adrenal weights. Histologically, DEXA-treated placentas appeared smaller than controls and showed signs of necrosis and pyknosis. Treated animals that were permitted to carry their litters to term did not deliver naturally, and most of their fetuses were dead when excised 1 day postmaturely.     

Treatment of pregnant rats with haloperidol delays the onset of sexual maturation in female offspring

Summary Treatment of pregnant rats with haloperidol (1 mg/kg/day) during the last week of gestation induces a significant delay in sexual maturation of female offspring.This study was supported by a Canadian MRC grant, No. MA-7131.     

Genetic determinants of individual differences in avoidance learning: Behavioral and endocrine characteristics

Bidirectional genetic selection for good and poor active avoidance learning in a shuttle box has been carried out in three independent laboratories using remarkably similar discrete-trial training procedures. The resulting strains are known as the Roman High and Low Avoidance (RHA and RLA), the Syracuse High and Low Avoidance (SHA and SLA) and the Australian High and Low Avoidance (AHA and ALA) strains, respectively. An additional unidirectionally selected strain, known as the Tokai High Avoider (THA) strain was developed in Japan using a free-operant Sidman avoidance procedure in a Skinner box. This paper reviews the selection of the Syracuse strains, enumerates the various behavioral and endocrine characteristics of the strains, and compares them to the other similarly selected strains. The behavioral work suggests that genetic selection from diverse breeding stocks has resulted in common characteristics that differentiate the strains in the emotional, not learning, domain. The endocrine data, however, are somewhat at odds. The Syracuse strains differentiate one way with respect to endocrine function, and the Roman strains differentiate in the opposite way. We suggest, therefore, that the endocrine correlates are not tightly linked to the avoidance genotype. Genetic analysis of all of the selected strains for both the avoidance phenotype and the endocrine correlates will be needed to test this hypothesis.Preparation of this paper was supported by research grant MH-39230-3 from the National Institute of Mental Health.     

Inhibition of ovulation in rats by antagonists to serotonin and by a new tricyclic compound.

The ovulation inhibiting activity in adult rats of the 5HT-antagonists cyproheptadine, mianserin and methysergide is shown. Furthermore the activity of a newly synthetized Cycloheptathiophenederivative, compound 26-921, which inhibits LH-secretion and consequently ovulation, is described.     

Inhibition of ovulation in rats by antagonists to serotonin and by a new tricyclic compound

Summary The ovulation inhibiting activity in adult rats of the 5HT-antagonists cyproheptadine, mianserin and methysergide is shown. Furthermore the activity of a newly synthetized Cycloheptathiophenederivative, compound 26–921, which inhibits LH-secretion and consequently ovulation, is described.     

Dexamethasone suppression of ovulation in PMS-treated immature rats.

A single injection of 2.0 mg/kg dexamethasone (DXM) administered at 51 h after pregnant mare serum gonadatropin (PMS) treatment inhibited both ovulation and luteinization. S.c. injection of human chorionic gonadotropin (HGG) caused ovulation and luteinization in DXM-PMS-treated rats, whereas treatment with ACTH failed to overcome the DXM inhibitory effect. These findings are interpreted to indicate that DXM inhibits ovulation through a mechanism which might involve the central nervous system.     

Dexamethasone suppression of ovulation in PMS-treated immature rats

Summary A single injection of 2.0 mg/kg dexamethasone (DXM) administered at 51 h after pregnant mare serum gonadatropin (PMS) treatment inhibited both ovulation and luteinization. S.c. injection of human chorionic gonadotropin (HGG) caused ovulation ond luteinization in DXM-PMS-treated rats, whereas treatment with ACTH failed to overcome the DXM inhibitory effect. These findings are interpreted to indicate that DXM inhibits ovulation through a mechanism which might involve the central nervous system.     

Deciduoma formation in rats with cornified vagina

Summary In female rats given a single injection of 1.25 mg 5-dihydrotestosterone during neonatal life, reactivity of the vaginal mucosa to hormones was permanently altered, so that the rats, when adult, could show vaginal cornification under the hormonic conditions supportive of development of deciduomata in the uterus.We wish to thank Prof.T. Kimoto of Kawasaki Medical College for valuable advice and information.     

Embryonic death in mouse due to lead exposure.

Female mice which displayed a vaginal plug after mating were given a diet containing 0, 0.125, 0.250, 0.500% of lead as lead acetate and were dissected 16 to 18 days later. Lead treatment was found to reduce significantly the incidence of pregnancies and to increase the postimplantation loss in the pregnant females.     

Embryonic death in mouse due to lead exposure

Summary Female mice which displayed a vaginal plug after mating were given a diet containing 0, 0.125, 0.250, 0.500% of lead as lead acetate and were dissected 16 to 18 days later. Lead treatment was found to reduce significantly the incidence of pregnancies and to increase the postimplantation loss in the pregnant females.