Reduced hypothermic and hypnotic responses to ethanol in PACAP-deficient mice

Using pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient mice, we investigated whether PACAP is involved in the intoxicating effects of ethanol. The structure of PACAP is highly conserved during evolution, and in Drosophila, loss-of-function mutations in a PACAP-like neuropeptide gene, amnesiac, result in impairment of memory retention and increased sensitivity to ethanol. In mice, PACAP deficiency is associated with impaired memory performance and hippocampal long-term potentiation (LTP), however, sensitivity to ethanol has not been well investigated. Here, we addressed this issue in our recently developed PACAP-deficient mice. Sleep time (duration of the loss of righting reflex) was markedly shortened in PACAP-deficient mice compared with wild-type, although latency to the loss of righting reflex was not different between the two groups. Ethanol-induced hypothermia in wild-type control mice was significantly reduced in PACAP-deficient mice. Blood ethanol levels were not different between the two groups, excluding the possibility of increased ethanol metabolism. Thus, in contrast to that in Drosophila, PACAP deficiency in mammals caused a reduced sensitivity to ethanol. However, in both cases, PACAP or amnesiac products are likely to play significant roles in modifying the intoxicating effects of ethanol.     

Reduced reproductive performance in androgen-resistant Tfm/Tfm female mice

Androgen-resistant female mice (Tfm/Tfm) homozygous for the mutant gene Tfm were bred by making use of males chimaeric for the Tfm gene. All seven Tfm/Tfm females found were fertile, confirming that a normal level of androgen receptor protein is not essential for reproduction in female mice. However, when five of the seven were studied throughout their reproductive life they proved to have impaired reproductive performance and premature cessation of reproduction. No impairment of reproduction was seen in heterozygous Tfm/+ females. The ovarian histology suggested that in Tfm/Tfm the normal ageing processes were accelerated. This work is consistent with the work of others in that androgen is involved in the control of follicular maturation and atresia, and that the effect is mediated by the androgen receptor coded by the Tfm locus.     

Urine-marking by female mice throughout their reproductive cycle.

It is commonly believed that the scent-marking activity of female mammals is elevated when they are sexually receptive, yet urine-marking by female mice does not vary in relation to their estrous cycles. We examined the marking behavior of female mice during their reproductive cycle with attention to their postpartum period of sexual receptivity. In the first experiment, females were allowed to mark prior to mating, during gestation, on the evening of parturition, during lactation, and after weaning their pups. They were exposed to a male or female mouse or nothing at each testing period in a counter-balanced fashion. Overall, the subjects marked most frequently in the presence of a male stimulus; their marking rates did not differ when they were exposed to another female or to nothing. The females' marking remained relatively steady through gestation, declined dramatically at parturition, then gradually returned to the levels observed prior to mating. In the second experiment, multiparous females were allowed to mark while they were simultaneously lactating and pregnant. Compared to unmated females, the subjects' marking frequency was low at parturition, declined further to its lowest level about 1 week later, then regained the preceding low level prior to weaning the initial litter and delivering the next. Together these results demonstrate that urine-marking by female mice is diminished just after parturition. Thus, in contrast to some other species, the marking behavior of female mice apparently is not enhanced around the time they are sexually receptive. Because female mice generally mark most frequently when males are nearby, we postulate that a major function of this behavior is to evoke endocrine and behavioral responses in proximate males rather than to attract distant males.     

Early experience and parent-of-origin-specific effects influence female reproductive success in mice

Recent studies on mammals investigating parent-of-origin-specific effects such as genomic imprinting and maternal effects have demonstrated their impact on short-term measures of fitness, for example offspring growth. However, the long-term fitness consequences of parent-of-origin-specific effects and their role outside the immediate mother-offspring interaction remain largely unexplored. Here, we show that female mice mated to males that inherited the same set of paternal and maternal genes as themselves have a higher reproductive success than females mated to males of reciprocal genotype. Furthermore, we demonstrate that the early social environment experienced by an individual influences its reproductive success. Females raised with unrelated siblings in a mixed litter had a subsequent lower reproductive success than those that were fostered together with all their biological siblings in unmixed litters. Our results highlight the important influence of parent-of-origin-specific effects and conditions in early development on long-term reproductive success in mammals and suggest that parent-of-origin-specific effects may provide the underlying mechanism for beneficial coadaptation between genotypes, for example, in mate choice.     

Seasonal effects on female reproductive functions in the bovine (Indian breeds)

Reproductive function is mediated by season in the Indian breeds of cattle ($\text{Bos}$$\text{indicus}$). The reproductive endocrinology of $\text{Bos}$$\text{indicus}$ cattle differs from that of $\text{Bos}$$\text{taurus}$ breeds; the estrus is shorter and less intense and occurs late in relation to an estrogen stimulus. Moreover, the $\text{Bos}$$\text{indicus}$ female has a smaller preovulatory surge of luteinizing hormone (LH), which occurs earlier relative to the onset of estrus, and she ovulates sooner after the onset of estrus. The corpus luteum is smaller and contains less progesterone, and the serum progesterone concentration is lower in $\text{Bos}$$\text{indicus}$ females. Furthermore, they have fewer preovulatory LH surges than $\text{Bos}$$\text{taurus}$ females and their luteal cells are less responsive to LH in vitro during the winter. Their fertility is lower during the late fall and winter months. For $\text{Bos}$$\text{indicus}$ cattle, recovery of transferable embryos and survival of embryos in the recipient are at their maximum from July through October.     

Effect of pelvic endometrial implants on overall reproductive functions of female rats

The effects of pelvic endometrial implants on the overall reproductive potential of female rats were investigated. After homologous transplantation in the peritoneum, the ectopic endometrium developed into highly vascularized nodes that gradually increased in mass until the 9th week postsurgery and then plateaued. In the presence of these implants, overall reproductive function was adversely affected. The effect was of greatest magnitude during 50-70 days posttransplantation. As compared with values in corresponding controls, ovulation was reduced by 43% (6 of 14) (p < 0.05), mating rate was reduced by 44% (12 of 27) (p < 0.025), and premature termination of pregnancy occurred in 34% (5 of 15) of rats. Wastage of pregnancy, which included complete termination or reduction of fetal number, occurred during the postimplantation course of gestation. Furthermore, 100% of the rats with transplants failed to respond to the copulomimetic stimulation for the induction of pseudopregnancy (p < 0.01, compared with corresponding controls). However, on exposure to vasectomized males, 46% (6 of 13) of these rats exhibited development of pseudopregnancy (p < 0.05, compared with corresponding group receiving copulomimetic stimulation). Increased rate of mating failure and differential pseudopregnancy rates after copulomimetic and natural cervical stimulation suggest that the rats with endometrial explants possibly had an absence or a short appearance of behavioral estrus. Hormonal assessment during the preovulatory phase showed a tendency toward lower mean levels of preovulatory estradiol and significantly lower LH (p < 0.01) and progesterone (p < 0.01) concentrations. The adversely affected reproductive functions may be a secondary consequence of these altered endocrine milieus.     

Identification of genetic regions of importance for reproductive performance in female mice

Both environmental and genetic factors can dramatically affect reproductive performance in mice. In this study we have focused on the identification of genetic regions, quantitative trait loci (QTL), which affect the breeding capacity of female mice. We have identified polymorphic microsatellite markers for the mouse strains used and performed a genomewide scan on 237 females from a gene-segregating backcross between a high breeder and a relatively poor breeder. The high-breeder mouse strain we used is the inbred NFR/N mouse (MHC haplotype H-2q), which has extraordinary good breeding properties. The moderate breeder chosen for F(1) and N2 progeny was B10.Q, which is a genetically well-characterized MHC-congenic mouse of the H-2q haplotype. Each of the 237 females of the N2 generation was allowed to mate twice with MHC-congenic B10.RIII (H-2r) males and twice with B10.Q males. A predetermined number of phenotypes related to reproductive performance were recorded, and these included litter size, neonatal growth, and pregnancy rate. Loci controlling litter size were detected on chromosomes 1 (Fecq3) and 9 (Fecq4). The neonatal growth phenotype was affected by Fecq3 and a locus on chromosome 9 (Neogq1). On chromosome 11 two loci affecting the pregnancy rate (Pregq1 and Pregq2) were identified. Furthermore, on chromosomes 13 and 17 we found loci (Pregq3 and Pregq4) influencing the outcome of allogeneic pregnancy (allogeneic by means of MHC disparity between mother and fetuses). A locus on chromosome 1 affecting maternal body weight was also identified and has been denoted Bwq7. It is well known that reproductive performance is polygenically controlled, and the identification of the major loci in this complex process opens the possibility of investigating the natural genetic control of reproduction.     

Comparative analysis of functions of cow and reindeer female reproductive organs: Progesterone content in vessels of reproductive organs

Progesterone content in blood from paired ovarian and uterine veins as well as from jugular veins of cows and reindeers was studied in the estrous cycle lutein phase and at the earlier stages of pregancy. In the both species, maximal progesterone concentration was detected in blood from vein of the ovary carrying corpus luteum (p < 0.001). In cows, a higher hormone concentration, as compared with jugular vein, has also been determined in vein of the uterus horn closest to ovary with corpus luteum (p < 0.01). In reindeers, blood from all studied vessels of reproductive organs had the progesterone concentration that was statistically significantly higher (p < 0.001) than that from jugular vein. In cows, progesterone concentration in blood from the ovarian vein was found to be higher when corpus luteum was located on the right ovary (p < 0.05) as compared with left-side corpus luteum location. No functional asymmetry of ovaries was revealed in reindeers. A possible role of mechanisms of the hormone local transport between ovary and uterus in adaptation of ruminants to reproduction under Nordic conditions is discussed.     

The transport of morphologically abnormal sperm in the female reproductive tract of mice

Mice of the PL/J strain exhibit a high percentage of morphologically abnormal sperm and provide a model for studying the function of abnormal sperm. The ability of such sperm to reach the site of fertilization within the female reproductive tract has been investigated. We have found a decrease in the percentage of structurally abnormal sperm within the population that reaches the oviduct. This observation suggests either that there is an active selection against abnormal sperm or that they are physiologically disadvantaged in reaching the site of fertilization.     

GRP78 expression and immunohistochemical localization in the female reproductive tract of mice

The 78-kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum chaperone, with multiple functional roles in protein processing and provision of cellular protection. However, the physiological role of GRP78 in embryo development is not clear. Localization of GRP78 and expression of its mRNA in the reproductive organs throughout the estrous cycle in mice were investigated by immunohistochemistry and real-time polymerase chain reaction, respectively. Whereas there was intense staining for GRP78 in the oviduct at estrus, the ciliated cells of isthmus had better staining than those of infundibulum and ampulla at all phases of the cycle. Furthermore, GRP78 was located in the uterine luminal and glandular epithelial cells throughout the estrous cycle, particularly during the estrus phase. However, levels of GRP78 mRNA in the oviduct and uterus varied during the cycle, with peaks at estrus. In conclusion, GRP78 expression varied with the phase of the murine estrous cycle; this might be related to gamete transport, fertilization and early development of the zygote/embryo.     

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.     

Sexual selection drives the coevolution of male and female reproductive traits in Peromyscus mice

When females mate with multiple partners within a single reproductive cycle, sperm from rival males may compete for fertilization of a limited number of ova, and females may bias the fertilization of their ova by particular sperm. Over evolutionary timescales, these two forms of selection shape both male and female reproductive physiology when females mate multiply, yet in monogamous systems, post-copulatory sexual selection is weak or absent. Here, we examine how divergent mating strategies within a genus of closely related mice, Peromyscus, have shaped the evolution of reproductive traits. We show that in promiscuous species, males exhibit traits associated with increased sperm production and sperm swimming performance, and females exhibit traits that are predicted to limit sperm access to their ova including increased oviduct length and a larger cumulus cell mass surrounding the ova, compared to monogamous species. Importantly, we found that across species, oviduct length and cumulus cell density are significantly correlated with sperm velocity, but not sperm count or relative testes size, suggesting that these female traits may have coevolved with increased sperm quality rather than quantity. Taken together, our results highlight how male and female traits evolve in concert and respond to changes in the level of post-copulatory sexual selection.     

Male and female reproductive toxicity induced by sub-chronic ethanol exposure in CF-1 mice

Since genetic damage induced by ethanol exposure is controversial and incomplete and because germ and somatic cells constitute bioindicators for monitoring reproductive toxicity and genotoxic actions of ethanol consumption, the purpose of the present investigation was to evaluate morphological sperm, oocyte alterations and parental genotoxic effects after sub-chronic ethanol intake in the CF-1 outbred mouse strain. Ethanol 10% was administered to CF-1 adult male (treated males, TM) and female (treated females, TF) mice for 27 days, whereas water was given to controls from both sexes too (CM and CF). Post-treatment micronucleus frequency (MN-PCE/1,000/mouse) and gamete morphology were evaluated. To test whether change of female reproductive status results in maternal genotoxicity, CF-1 females received ethanol 10% (exposed group, periconceptionally treated females (PTF)) or water (control group, pregnant control females (PCF)) in drinking water for 17 days previous and up to 10 days of gestation. TM had a high percentage of abnormal spermatozoa vs CM (p < 0.001) and elevated parthenogenetic activated oocyte frequency appeared in TF vs CF (p < 0.001). Sub-chronic ethanol ingestion induced increased MN frequency in TM and TF (p < 0.01). In PTF, where blood alcohol concentrations were between 19–28 mg/dl, very significantly increased MN frequency was found vs PCF (p < 0.01), whereas MN values were similar to TF. These results show that sub-chronic alcohol ingestion in CF-1 mice produces sperm head dysmorphogenesis and oocyte nuclear anomalies, suggesting that morphological abnormalities in germ cells are probably related to parental genotoxicity after ethanol consumption.     

Schistosome female reproductive development

Schistosome parasites have evolved to produce a number of unique features in their life history; one of these is separate sexes. This has, in turn, led to a novel interplay between the male and female parasite that has been recognized for over 50 years: the growth and reproductive development of the female parasite is in some way regulated by the male schistosome. Early classical and later experimental studies established that the presence of the male schistosome is necessary not only for the initiation of female development but also for the maintenance of her mature state. The male parasite regulates the reproductive development of the female, partly by providing a stimulus that is necessary for the development of the vitelline gland. The cells of the vitelline gland provide nutrients and shell precursors for the egg. Also in this review by Philip LoVerde and Li-ly Chen, it is interesting to note that recent molecular studies have confirmed early work by showing that gene expression in the female parasite is developmentally regulated in a tissue-specific manner and that this gene expression is controlled by the presence of a male parasite.     

Oral administration of pharmacological doses of vitamins C and E reduces reproductive fitness and impairs the ovarian and uterine functions of female mice

This study aims to ascertain whether oral administration of pharmacological doses of Vitamins C and E has any detrimental effect on reproductive fitness of female mice. We fed hybrid female mice from the first day of weaning a standard diet supplemented or not supplemented with pharmacological doses of Vitamins C and E. At the age of 28 weeks, we individually caged females with a male for the rest of their reproductive life. We performed a series of mating experiments to ascertain the number of oocytes ovulated and the potential for embryo development in vitro to the blastocyst stage and in vivo to Day 12 of gestation. The antioxidant diet decreased the frequency of litters, litter size, total number of offspring born and survival of male pups to weaning. This effect was associated with lower number of corpora lutea in the left ovary, decreased percentage of viable fetuses, and higher number of fetal resorptions in the left uterine horn when compared to the control group. The strategy of supplementing the diet with antioxidant vitamins to prevent the age associated decrease in reproductive potential should not be implemented in human beings until a safe and efficient diet is designed.