Effect of cultural inheritance of reproductive compensation on the incidence of a sex-linked lethal disease

For a sex-linked recessive lethal disease, a model is constructed to study reproductive compensation for having at least one normal male with partial cultural inheritance. The equilibrium frequency of heterozygous females depends on the probability that a female offspring of the compensating parents will not compensate, α, the probability that a female offspring of the non-compensating parents will compensate, β, and the mutation rate, u. When α = 0, the equilibrium frequency of heterozygous females is given by √2u, whereas when α ≠ 0 it is given by 2[{β +(2α + β) (α + β)}/{α(α + β)}]u.Then, the proportion of affected males due to fresh mutations is much smaller than Haldane's estimate of $\text{1}\text{3}$ without reproductive compensation.     

Faced with inequality: chicken do not have a general dosage compensation of sex-linked genes

Background  

The contrasting dose of sex chromosomes in males and females potentially introduces a large-scale imbalance in levels of gene expression between sexes, and between sex chromosomes and autosomes. In many organisms, dosage compensation has thus evolved to equalize sex-linked gene expression in males and females. In mammals this is achieved by X chromosome inactivation and in flies and worms by up- or down-regulation of X-linked expression, respectively. While otherwise widespread in systems with heteromorphic sex chromosomes, the case of dosage compensation in birds (males ZZ, females ZW) remains an unsolved enigma.     

Increased incidence of abnormal foetuses in the offspring of cyclophosphamide-treated male mice

The incidence of morphologically abnormal foetuses in the litters of cyclophosphamide (CP)-treated male mice was investigated and compared with control values. In two experiments (100 mg/kg) CP was shown to increase the incidence of grossly abnormal foetuses over that seen in the controls, although neither was statistically significant in isolation. When the probabilities from the two tests of significance were combined using the method of Fisher the result was significant (P = 0.02). These results suggest that an acute exposure to a mutagen in male mice can cause genetic damage that results in an increased incidence of phenotypically abnormal offspring. However, the large numbers of animals required and the variable control level of abnormalities, indicate that this dosing regimen is an inefficient method of studying the genetic mechanisms responsible for the effects seen.     

Effects of male rat urine on reproductive and developmental parameters in the dam and her female offspring

This study investigated the direct and indirect effects of male Norway rat (Rattus norvegicus) urine on reproductive, developmental, and fecundity parameters in the dam and her female offspring. Twenty-two dams and litters were studied: 11 in male urine and 11 in distilled water conditions. Only dams were exposed to male urine (or distilled water) from days 14 to 29 postpartum. Significant effects found for the dams exposed to male urine (compared to those only exposed to distilled water) included (i) the second lactational estrus was delayed by 2 days, (ii) vaginal opening and first estrus were 1 day later for female offspring, (iii) the first estrous cycle after vaginal opening was also shorter for their offspring, and (iv) female offspring subsequently produced larger litters than female offspring from dams only exposed to distilled water. Thus, urine from males had direct effects on the timing of the second lactational estrus in dams and indirect effects (mediated by the dam) on developmental and reproductive parameters of her female offspring. Taken as a whole, these results suggest that pheromones in Norway rats may be complex in their effects, context-dependent, and only fully revealed in ecologically relevant contexts. Further study is required to determine whether these effects occur and have biological functions in natural populations.     

Comparison of the effects of gossypol, estradiol-17 beta and testosterone compensation on male rat reproductive organs

The effects of gossypol acetic acid (GAA) were compared with those induced by estradiol-17 beta (E2), testosterone, and a combination of these steroids. GAA was administered s.c. to adult rats at doses of 25 to 30 mg . kg BW . day for 30 days, while steroids in polydimethylsiloxane tubing of various lengths were implanted s.c. for 30 days or longer. GAA and E2 at the doses used had similar effects: they caused a graded atrophy of sex organs, discriminative degeneration of spermatogenic cells, impairment of Sertoli cells, decrease in serum testosterone, reduction in androgen receptor binding and retardation in body growth. Supplementing GAA and E2 treatments with 14-cm testosterone implants had a counteracting effect on organ weight losses: seminal vesicles recovered above, ventral prostate within and epididymides below control values, whereas the testes did not respond. The organs most refractory to supplementation therapy were those in which GAA and E2 were most effective in depressing androgen receptor binding. Aside from having similar antiandrogenic effects as E2 and other steroids, GAA induced a specific flagellar syndrome which testosterone therapy could not prevent, indicating that this action is hormonally independent.     

The incidence of the various genotypes in a population showing a sex-linked recessive character

Summary Although the inheritance of a sex-linked recessive trait is well known, not all consequences are sufficiently realised. Therefore, the facts are presented once more in a new form.All populations that are unaffected by selection tend to stabilisation. When this has been reached the five different genotypes are bound by definite and rather simple numerical relations. Whereas the percentages of normal (X-) and affected (x-) males, and also those of homozygous normal (XX) and affected (xx) females may vary between 0 and 100, the percentage of heterozygous females (Xx) in a stable population never exceeds 50%.     

Effect of estrogen deprivation on the reproductive physiology of male and female primates

The availability of CGS 16949A, CGS 20267 and CGP 47645, a series of aromatase inhibitors (AIs) having high specific activity and specificity, made possible this study wherein the need for estrogen (E) for regulating (a) follicular maturation/ovulation, luteal function and pregnancy establishment, and (b) testicular function of the bonnet monkey (Macaca radiata) has been examined. Generally these compounds, used in the range of 500 μg to 2.5 mg/day did not inhibit follicular maturation although they did reduce E levels. Although low doses had no effect on ovulation it appears that relatively high doses of CGS 20267 and CGP 47645 could be inhibiting it. Three oral doses of letrozole (CGS 20267, each dose of 2 mg) during the follicular phase resulted in the formation of multiple follicles in cycling females, and these could be ovulated by exogenous hCG (1000 IU) treatment. Although administration of AI during the early luteal phase had no effect on progesterone (P) production, it prevented pregnancy establishment. Whereas AI administration in the female had no significant effect on luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels (except at high drug dosages), it significantly increased serum testosterone (T) levels in the male. Sustained high levels of T (30–50 ng/ml) could be maintained for 100 days by administering 2.5 mg of CGP 47465 orally once in 5 days. Blockade of E synthesis in the male led to the disruption of testicular germ cell transformation, which in turn resulted in a significant reduction in sperm production. These studies with aromatase inhibitors in the monkey suggest that these compounds have a potential for use as fertility regulating agents in both the male and female primate.     

Females allocate differentially to offspring size and number in response to male effects on female and offspring fitness

Female investment in offspring size and number has been observed to vary with the phenotype of their mate across diverse taxa. Recent theory motivated by these intriguing empirical patterns predicted both positive (differential allocation) and negative (reproductive compensation) effects of mating with a preferred male on female investment. These predictions, however, focused on total reproductive effort and did not distinguish between a response in offspring size and clutch size. Here, we model how specific paternal effects on fitness affect maternal allocation to offspring size and number. The specific mechanism by which males affect the fitness of females or their offspring determines whether and how females allocated differentially. Offspring size is predicted to increase when males benefit offspring survival, but decrease when males increase offspring growth rate. Clutch size is predicted to increase when males contribute to female resources (e.g. with a nuptial gift) and when males increase offspring growth rate. The predicted direction and magnitude of female responses vary with female age, but only when per-offspring paternal benefits decline with clutch size. We conclude that considering specific paternal effects on fitness in the context of maternal life-history trade-offs can help explain mixed empirical patterns of differential allocation and reproductive compensation.     

Effect of tamoxifen citrate on reproductive parameters of male dogs

Tamoxifen is a synthetic, nonsteroidal Type I antiestrogenic compound that competitively blocks estrogen receptors with a mixed antagonist-agonist effect. The manifestation of these different actions depends on each species, organ, tissue and cell type considered. Very little is known about the effect of antiestrogens in dogs. The objectives of this study were to determine the effects of tamoxifen citrate on some testis, prostate, hormone, and semen parameters in seven Beagle dogs with uncomplicated spontaneous benign prostatic hyperplasia. Two dogs were normospermic, four were oligozoospermic, and one was azoospermic. The dogs were allocated to a control pre-treatment period, followed by a treatment period, and five post-treatment periods (the duration of each period was 4 weeks). During the treatment period, 2.5mg tamoxifen citrate was given p.o. daily for 28 days to all the dogs. Maximum scrotal width, testicular consistency, libido semen parameters, prostatic volume, serum testosterone concentrations, and side effects were assessed. Tamoxifen negatively affected testis size and libido (P<0.01), and decreased prostatic volume (P<0.01) and testosterone concentrations during treatment. Semen quality deteriorated to nadir values (P<0.01) approximately one spermatic cycle after treatment and returned to pre-treatment values on the second cycle after treatment in all the dogs, except one young oligoazoospermic dog, in which the sperm count was higher ( P<0.01 ) at that time. No side effects were observed and fertility was conserved at the end of the study. Tamoxifen acted more like an agonist than antagonist on the gonadal axis and, therefore, upon both the prostate and testis. Therefore, tamoxifen may have therapeutic applications in dogs.     

Maternal environment and the reproductive function of the offspring

Fetal programming of metabolic diseases is now a well established concept. The scope of the Developmental Origins of Health and Disease has, however, widened and led to the identification of new targets of fetal programming, notably effects on reproductive function. Epidemiologic studies about maternal nutrition and effects on offspring's fertility are rare, but a link between impaired fetal growth, possibly caused by maternal malnutrition, and reproductive function, has been established. The methodologic limitations inherent to human epidemiologic studies can be complemented through the use of animal models, which enable experimental studies on maternal environment and its effect on reproductive functions of the offspring. Altogether, an interaction between inappropriate maternal nutrition (excess or reduced nutritional intake, micronutrient unbalance, or alcohol intake) and reproductive maturation of the offspring has been shown in a majority of experiments as summarized in this review. The exact processes through which maternal nutrition or maternal environment affect reproductive function in the offspring remain unclear but epigenetic modifications are a clear link. Further studies are needed to better understand the mechanisms involved, identify the crucial critical periods, and prevent or treat the adverse effects.     

Studies on the induction of sex-linked recessive lethal mutations in Drosophila melanogaster by nitroheterocyclic compounds

24 nitroheterocyclic compounds were investigated for their capacity to induce sex-linked recessive lethals in Drosophila, by the adult feeding technique, and in some cases injection or larval-feeding methods. Out of 9 5-nitroimidazoles, ZK 26.173 and ZK 25.095 (moxnidazole) were clearly active whereas nimorazole and ronidazole were marginally mutagenic. Out of 10 5-nitrofurans, nitrovin, furazolidone and furaltadone were unambiguously mutagenic, whereas nitrofurantoin was a borderline case. Nitrofurans were active at lower molar concentrations than nitroimidazoles. Out of a group of 5 related nitro compounds (2 nitrothiophenes, picrolonic acid, niridazole and 4-NQO), only 4-NQO was clearly mutagenic, when fed to larvae. Experiments with germ-free flies showed that, for ZK 26.173 and furazolidone, the gut flora of Drosophila do not play a role in the activation of the compounds to mutagenic metabolites. Furazolidone, 4-NAO, ZK 26.173, ZK 25.095 and furaltadone were tested in mal and cin strains, both of which lack xanthine dehydrogenase and aldehyde oxidase. The latter enzyme and xanthine oxidase are known to carry out nitro reduction in mammalian tissues. For ZK 26.173, the mutation frequencies were drastically reduced in the enzyme-deficient strains, indicating the involvement of one of these enzymes in the activation of this substance.     

Male mice produced by in vitro culture have reduced fertility and transmit organomegaly and glucose intolerance to their male offspring

It has been reported that suboptimal in vitro culture (IVC) of mouse embryos can affect the postnatal expression of epigenetically sensitive alleles, resulting in altered postnatal growth, organ dimensions, health, and behavior in the offspring. Although these detrimental impacts on the offspring are well described, the relative contribution of the IVC-produced fathers is unclear. In this work, we have analyzed if suboptimal IVC (achieved by altering the culture medium by the addition of FCS) can affect male fertility and if organ size and glucose clearance, two of the adverse effects produced by suboptimal IVC conditions, were transmitted to the next two generations. IVC-produced males had lower sperm concentrations (5.8 × 10(6) spermatozoa in IVC vs. 14.5 × 10(6) spermatozoa in control), and these sperm exhibited decreased overall motility (49.6% vs. 72.8% in control) and progressive motility (22.6% vs. 32.2% in control). Fertility tests demonstrated that the percentage of pregnancies was reduced for IVC males (35% for IVC-produced males vs. 86% for in vivo controls). These features were related to a modified gene expression pattern in adult male testes, showing an altered gene expression in genes involved in DNA repair and apoptosis that was confirmed by TUNEL assay. Regarding the IVC related adverse phenotype transmitted to offspring, male glucose intolerance was shown only in F1 and F2 male but not female offspring. The same occurred with male abnormalities in the organ size of the liver, which were transmitted to F1 and F2 males but not to F1 females; moreover, analysis of the F0, F1, and F2 males revealed greater coefficients of variance in body weight and glucose intolerance than the control group. Finally, we analyzed, through gene silencing, the effect of IVC on the mRNA expression at the blastocyst stage for 11 known gene expression modifiers of epigenetic reprogramming. Suboptimal IVC reduced the expression of Kap1, Sox2, Hdac1, Dnmt1, and Dnmt3a, suggesting a molecular epigenetic role for gene expression modifiers in the origin and transmission of these abnormal phenotypes.