Influences of female partner preference on potential reproductive outcome in Japanese macaques.

The immediate effects of female partner preference on male mating behaviors and its potential influence on male reproductive success and conception in the Japanese macaque (Macaca fuscata) were analyzed. Although male dominance interactions probably led to low-ranking males having more single-day consortships and high-ranking males more multi-day consortships, dominant males were unable to prevent females from mating with preferred subordinate males. Ultimately, there was no marked difference in the number of estimated offspring sired. Females chose not to mate with certain males and actively mated with others, suggesting that female partner preferences do affect conception. Evidence for this was found in paternity estimates, which reflected observed preferences for particular middle-ranking young adult males.     

Effect of exogenous progesterone and estradiol on the process of embryonic implantation in lead intoxicated female mice]

Exposure of female mice to high doses of lead from the first day of pregnancy inhibits embryonic implantation. Animals exposed to 0.5% of lead in diet received injections of progesterone and estradiol, from day 4 to day 7 or from day 5 to day 8 of pregnancy. Such treatments induced implantation in respectively 50 and 80% of the mice. In controls, implantation was observed in 60% of the animals. In animals exposed to lead but not hormone-treated, no implantation was observed. The inhibition of implantation caused by lead seems thus to be due mainly to an action of this metal on the hormonal balance of the exposed mother, and this confirms our earlier results.     

Effect of selection for development rate on reproductive onset in female mice.

This research reports analyses of correlated response in reproductive onset in ICR mice after 23 generations of restricted index selection for divergent body weight gain, early (birth-10 days) or later (28-56 days) in life. Long-term selection altered growth trajectories and 56 day body weight of individuals under different selection regimes in this study. Mice in lines under early selection have the same percentage mature weight at vaginal opening as controls (63%). Vaginal opening is delayed in mice selected for slow early growth, which take longer to reach what appears to be a weight threshold. In contrast, individuals in lines selected for later slow growth undergo vaginal opening at the same age as controls, but at a lower weight and increased percentage mature weight. Pre-compensation or 'counter-balance growth' is observed in these lines, with mice selected for late enhanced growth reaching 52% of mature weight at vaginal opening while mice with late slow growth attain 71% of mature weight prior to vaginal opening. Only 42% of mice with late slow growth attain first oestrus by 56 days. We speculate this is a function of growth rate and fat/lean ratio. Mice with early slow growth show compensatory growth, reaching first oestrus at a similar time to controls. We conclude that selection for growth rate has asymmetrically affected reproductive onset, with lines selected for suppressed gains experiencing delays in the reproductive onset traits measured.     

Induction of male-typical aggression by androgens but not by estrogens in adult female mice

Ovariectomized adult CF-1 female mice were implanted with silastic capsules containing either testosterone (T), dihydrotestosterone (DHT), methyltrienolone (R1881), estradiol (E2), diethylstilbestrol (DES), or oil vehicle and were tested for aggressive behavior. The androgenic treatments (T, DHT, R1881) were highly effective in promoting male-like aggression while the estrogens (DES, E2) were completely ineffective. Subsequent receptor-binding studies confirmed assumptions about the specificity of DES, DHT, and R1881 binding to estrogen and androgen receptors in mouse hypothalamus.     

Influences of weather on reproductive function in female Song sparrows, Melospiza melodia

Prolonged and severe periods of inclement weather can retard gonadal development in early spring or disrupt the breeding cycle in summer. Previous investigations on the endocrine responses of free-living avian species to storms have been restricted almost entirely to males. This communication presents the endocrine responses of free-living female Song sparrows, Melospiza melodia, during gonadal recrudescence after a severe winter, and during storms in early spring and summer. As in males, gonadal recrudescence was delayed by the severe winter weather, and this effect was exacerbated by an aseasonal snow storm in early spring. Unlike males, female Song sparrows did appear to be stressed by this snow storm, since body mass and fat deposit decreased, and plasma levels of corticosterone increased. A second storm in early summer did not, however, prove to be stressful to females, although males were apparently stressed by the same storm. At the time the early summer storm occurred, young had been fledged and were being fed mostly by the male. Females begin preparing for a second clutch of eggs and do not feed fledglings to the same extent as males. Thus it is possible that males are stressed by storms at this time, because they are feeding several young as well as themselves during a period of reduced availability of food, whereas females are feeding themselves only. These data suggest that, not only do the endocrine responses to inclement weather vary in relation to stage in the reproductive cycle when storms strike, but also that there are sex differences in those responses.     

Prenatal stress: effects on sexual receptivity in female rats

Pregnant primiparous rats were submitted to daily immobilization stress for 3 hour periods which were increased 15 minutes every third day. A considerable increase in the receptivity to the male was observed in the prenatally stressed females versus controls. Female offspring from both groups did not show any differences in body, adrenal, ovary and brain weights.     

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.     

Physiological doses of epinephrine in the human: chronotropic but not hyperglycemic or catecholaminotropic

Single physiological doses of epinephrine did not affect the blood sugar level of human volunteers though they caused a marked tachycardia that was accompanied by a strong transient sensation, typically described as fullness in the chest. Epinephrine did not cause the release of norepinephrine and/or dopamine in man, in contrast to three other vertebrates (lamprey, eel, and rat). In the human, as in the rat and cyclostomes, the glycemic effect of epinephrine occurs only during stress and/or unphysiological conditions, while the chronotropic effects are probably physiological from cyclostomes to man.     

Loss of gremlin delays primordial follicle assembly but does not affect female fertility in mice

The transforming growth factor beta (TGFB) protein family is renowned for its diverse roles in developmental biology including reproduction. Gremlin is a member of the differential screening-selected gene aberrative in neuroblastoma (DAN)/cerberus family of bone morphogenetic protein (BMP) antagonists. Recent studies on gremlin focus on its involvement in embryonic skeletal, lung, and kidney development. To define the role of gremlin (Grem1) in female reproduction, we analyzed postnatal folliculogenesis using global and conditional knockout (cKO) mice for gremlin. Grem1(-/-) mice die within 48 h after birth, and ovaries collected from neonatal Grem1(-/-) mice demonstrated reduced oocyte numbers and delayed primordial follicle development. Transplanting Grem1(-/-) neonatal ovaries showed that folliculogenesis proceeded to large antral follicle stage, but Grem1(-/-) ovaries contained corpora lutea-like structures not found in control-transplanted ovaries. However, Grem1 cKO mice had comparable fertility to control mice. These data suggest that gremlin plays a previously uncharacterized role in the regulation of oocyte numbers and the timing of primordial follicle development, but either it is not required for later folliculogenesis or its loss is possibly compensated by other BMP antagonists.     

Hypercalcemia produced by parathyroid hormone suppresses experimental autoimmune encephalomyelitis in female but not male mice

Besides its role in regulating serum levels of calcium and phosphorus, 1alpha, 25-dihydroxyvitamin D3 (1,25-(OH)2D3) has potent effects on the immune system and suppresses disease in several animal models of autoimmune disorders including experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. While the amount of 1,25-(OH)2D3 needed to prevent EAE is dependent on the gender of the mouse and amount of calcium available in the diet, the minimum levels of 1,25-(OH)2D3 sufficient to prevent disease cause hypercalcemia. To test if hypercalcemia independent of high levels of 1,25-(OH)2D3 can suppress EAE, we used a 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-hydroxylase) knockout mouse strain. Because these 1alpha-hydroxylase knockout mice lack the parathyroid hormone (PTH)-regulated enzyme that synthesizes 1,25-(OH)2D3, hypercalcemia from increased bone turnover was created by continuous administration of PTH without changing the circulating levels of 1,25-(OH)2D3. This PTH-mediated hypercalcemia generated after EAE induction prevented disease in female mice but not male mice. When hypercalcemia was prevented by diet manipulation, PTH administration no longer prevented EAE. We conclude that hypercalcemia is able to prevent EAE after disease induction in female mice.     

Downregulation of glutaredoxin but not glutathione loss leads to mitochondrial dysfunction in female mice CNS: implications in excitotoxicity

Oxidative stress, excitotoxicity and mitochondrial dysfunction play synergistic roles in neurodegeneration. Maintenance of thiol homeostasis is important for normal mitochondrial function and dysregulation of protein thiol homeostasis by oxidative stress leads to mitochondrial dysfunction and neurodegeneration. We examined the critical roles played by the antioxidant, non-protein thiol, glutathione and related enzyme, glutaredoxin in maintaining mitochondrial function during excitotoxicity caused by beta-N-oxalyl amino-L-alanine (L-BOAA), the causative factor of neurolathyrism, a motor neuron disease involving the pyramidal system. L-BOAA causes loss of GSH and inhibition of mitochondrial complex I in lumbosacral cord of male mice through oxidation of thiol groups, while female mice are resistant. Reducing GSH levels in female mice CNS by pretreatment with diethyl maleate or L-propargyl glycine did not result in inhibition of complex I activity, unlike male mice. Further, treatment of female mice depleted of GSH with L-BOAA did not induce inhibition of complex I indicating that GSH levels were not critical for maintaining complex I activity in female mice unlike their male counterpart. Glutaredoxin, a thiol disulfide oxidoreductase helps maintain redox status of proteins and downregulation of glutaredoxin results in loss of mitochondrial complex I activity. Female mice express higher levels of glutaredoxin in certain CNS regions and downregulation of glutaredoxin using antisense oligonucleotides sensitizes them to L-BOAA toxicity seen as mitochondrial complex I loss. Ovariectomy downregulates glutaredoxin and renders female mice vulnerable to L-BOAA toxicity as evidenced by activation of AP1, loss of GSH and complex I activity indicating the important role of glutaredoxin in neuroprotection. Estrogen protects against mitochondrial dysfunction caused by excitotoxicity by maintaining cellular redox status through higher constitutive expression of glutaredoxin in the CNS. Therapeutic interventions designed to upregulate glutaredoxin may offer neuroprotection against excitotoxicity in motor neurons.     

Enhanced muscle fatigue occurs in male but not female ASIC3-/- mice

Muscle fatigue is associated with a number of clinical diseases, including chronic pain conditions. Decreases in extracellular pH activates acid-sensing ion channel 3 (ASIC3), depolarizes muscle, protects against fatigue, and produces pain. We examined whether ASIC3-/- mice were more fatigable than ASIC3+/+ mice in a task-dependent manner. We developed two exercise protocols to measure exercise-induced muscle fatigue: (fatigue task 1, three 1-h runs; fatigue task 2, three 30-min runs). In fatigue task 1, male ASIC3+/+ mice muscle showed less fatigue than male ASIC3-/- mice and female ASIC3+/+ mice. No differences in fatigue were observed in fatigue task 2. We then tested whether the development of muscle fatigue was dependent on sex and modulated by testosterone. Female ASIC3+/+ mice that were ovariectomized and administered testosterone developed less muscle fatigue than female ASIC3+/+ mice and behaved similarly to male ASIC3+/+ mice. However, testosterone was unable to rescue the muscle fatigue responses in ovariectomized ASIC3-/- mice. Plasma levels of testosterone from male ASIC3-/- mice were significantly lower than in male ASIC3+/+ mice and were similar to female ASIC3+/+ mice. Muscle fiber types, measured by counting ATPase-stained whole muscle sections, were similar in calf muscles from male and female ASIC3+/+ mice. These data suggest that both ASIC3 and testosterone are necessary to protect against muscle fatigue in a task-dependent manner. Also, differences in expression of ASIC3 and the development of exercise-induced fatigue could explain the female predominance in clinical syndromes of pain that include muscle fatigue.     

Uncoupling protein 2, but not uncoupling protein 1, is expressed in the female mouse reproductive tract

Uncoupling proteins (UCPs) are transporters of the inner mitochondrial membrane. Whereas UCP1 is uniquely present in brown adipose tissue where it uncouples respiration from ATP synthesis and activates respiration and heat production, UCP2 is present in numerous tissues, and its exact function remains to be clarified. Two sets of data provided the rationale for this study: (i) the intriguing report that UCP1 is present in uterus of mice (Nibbelink, M., Moulin, K., Arnaud, E., Duval, C., Penicaud, L., and Casteilla, L. (2001) J. Biol. Chem. 276, 47291-47295); and (ii) an observation that Ucp2(-/-) female mice (homozygous matings) have smaller litters compared with Ucp2(+/+) animals (S. Rousset and A.-M. Cassard-Doulcier, unpublished observations). These data prompted us to examine the expression of UCP1 and UCP2 in the reproductive tract of female mice. Using wild type, Ucp1(-/-) mice, and Ucp2(-/-) mice, we were unable to detect UCP1 in uterus of mice with appropriate antibodies, and we conclude that the signal assigned to UCP1 by others was neither UCP1 nor UCP2. Using a polyclonal antibody against UCP2 and tissues from Ucp2(-/-) mice as controls, UCP2 was detected in ovary, oviduct, and uterus. Expression of Ucp2 mRNA was also observed in ovary and uterus using in situ hybridization analysis. Bone marrow transplantation experiments revealed that the UCP2 signal of the ovary was restricted to ovarian cells. UCP2 level in ovary decreased during follicular growth and increased during the pre-ovulatory period, during which aspects of an inflammatory process are known to exist. Because UCP2 down-regulates reactive oxygen species, a role in the regulation of inflammatory events linked to the preparation of ovulation is suggested.     

Seminal proteins but not sperm induce morphological changes in the Drosophila melanogaster female reproductive tract during sperm storage

In most insects, sperm transferred by the male to the female during mating are stored within the female reproductive tract for subsequent use in fertilization. In Drosophila melanogaster, male accessory gland proteins (Acps) within the seminal fluid are required for efficient accumulation of sperm in the female's sperm storage organs. To determine the events within the female reproductive tract that occur during sperm storage, and the role that Acps and sperm play in these events, we identified morphological changes that take place during sperm storage in females mated to wild-type, Acp-deficient or sperm-deficient males. A reproducible set of morphological changes occurs in a wild-type mating. These were categorized into 10 stereotypic stages. Sperm are not needed for progression through these stages in females, but receipt of Acps is essential for progression beyond the first few stages of morphological change. Furthermore, females that received small quantities of Acps reached slightly later stages than females that received no Acps. Our results suggest that timely morphological changes in the female reproductive tract, possibly muscular in nature, may be needed for successful sperm storage, and that Acps from the male are needed in order for these changes to occur.