Foetal Loss and Enhanced Fertility Observed in Mice Treated with Zidovudine or Nevirapine

Background

Health concerns for HIV-infected persons on antiretroviral therapy (ART) have moved from morbidity to the challenges of long-term ART. We investigated the effect of Zidovudine or Nevirapine on reproductive capacity across two mouse generations.

Methods

A prospective mouse study with drugs administered through one spermatogenic cycle. Mouse groups (16 males and 10 females) were given Zidovudine or Nevirapine for 56 days. Males were mated to untreated virgin females to determine dominant lethal effects. Twenty females (10 treated and 10 untreated) mated with the treated males per dose and gave birth to the F₁ generation. Parental mice were withdrawn from drugs for one spermatogenic cycle and mated to the same dams to ascertain if effects are reversible. The F₁ generation were exposed for another 56 days and mated to produce the F₂ generation.

Results

Foetal loss was indicated in the dominant lethal assay as early as four weeks into drug administration to the males. At the first mating of the parental generation to produce the F₁ generation, births from 10 dams/dose when the ‘father-only’ was exposed to Zidovudine (10, 100 and 250 mg/kg) was 3, 2 and 1 while it was 7, 1 and 4 respectively when ‘both-parents’ were exposed. Similarly births from the parental generation first mating when the ‘father-only’ was exposed to Nevirapine (5, 50 and 150 mg/kg) was 2, 2 and 0 while it was 6, 5 and 9 respectively when ‘both-parents’ were exposed. However, fertility was not significantly different neither by dose nor by the parental exposure. The F₁ mice mated to produce the F₂ generation recorded only one birth.

Conclusion

The dominant lethal analysis showed foetal loss occurred when the “fathers-only” were treated while fertility was enhanced when “both-parents” were on therapy at the time of mating.     

Influence of Low-Intensity Electromagnetic Field on Some Biological Parameters of Freshwater Crustaceans <Emphasis Type="Italic">Daphnia magna</Emphasis> Straus

We have studied the effects of a low-intensity electromagnetic field (EMF) with a frequency of 30 MHz in continuous-wave and amplitude-modulation modes on Daphnia magna in a laboratory culture. The exposure range is from 10 to 10000 s. We examine the parental generation (irradiated) and three subsequent (F₁–F₃) generations (nonirradiated). It is found that irradiation does not affect the total fertility of any specimen in four generations (P–F₃), except for continuous EMF exposure for 10000 s, which increases the total fertility in generations F₂ and F₃ by 23 and 43%, respectively. Electromagnetic radiation has a significant impact on offspring quality and causes fetal abnormalities in the offspring of all generations.     

Fertility of triploid hybrids of Prussian carp (<Emphasis Type="Italic">Carassius gibelio</Emphasis>) with common carp (<Emphasis Type="Italic">Cyprinus carpio</Emphasis> L.)

Fertility of backcross triploid hybrids containing one genome of Prussian carp and two genomes of common carp is investigated. The females of hybrids of Prussian carp and common carp (Prussian × common carp) are prolific and produce diploid gametes. Since males of such hybrids are sterile, their reproduction is realized by means of induced gynogenesis. Triploid progeny is obtained by backcrossing female Prussian × common carp with carp males. Among triploids obtained from hybrids F₁ and among hybrids of the first gynogenetic generation, there were no prolific specimens. However, in reproduction of diploid hybrids by means of gynogenesis during six generations, the female fertility in the backcross progeny is restored. From backcross triploid females (daughters of Prussian × common carp of the sixth gynogenetic generation), a viable triploid gynogenetic progeny and a tetraploid backcross (by carp) progeny are obtained. The obtained data may be considered as the experimental proof of the hypothesis of reticular speciation.     

Persistence of male sterility in strains issued from hybrids between two sibling species:Drosophila simulans andD. mauritiana

The cross between two sibling species,D. simulans andD. mauritiana, produced F₁ fertile females and sterile males. Backcrosses of these females to parental males resulted in the production of a small proportion of fertile males. From this second generation, four lines were propagated by mass mating and the frequency of fertile males was determined up to the 20th generation. In all cases, a linear increase of the proportion of fertile males was observed between the 2d and 8th generations and then the proportion remained stable at a level of 91%. From these observations several conclusions seem possible. (1) Male fertility was determined by several genes existing under different allelic conditions in the two sibling species; (2) the progressive restoration of male fertility was due to a normalizing selection which favored the homozygotes against the heterozygotes; (3) the persistence of a small frequency of sterile males after the 8th generation was the consequence of a balancing selection favoring the heterozygous condition (possibly in the females); (4) introgression of genes from one species into the genome of another species appeared capable of increasing the genetic heterogeneity of the population for a long time.     

Genetics of fertility restoration in cytoplasmic male sterile Phaseolus vulgaris L.

Summary Restoration of fertility in cytoplasmic male sterile Phaseolus vulgaris by line R-351 was controlled by a single gene. The restorer gene (Fr) displayed incomplete dominance leading to partial restoration of fertility in F₁ generations; full restoration was not achieved until the F₂ generation. Once full restoration of fertility was produced in the F₂ generation, no segregation for sterility was observed in subsequent generations derived from heterozygotes Frfr, either by testcrossing (restored × maintainer) or in F₃ progenies. Implications of the irreversible nature of this restoration are discussed.Florida Agr. Exp. Sta. Journal Series No. 7733     

Abnormally High Nourishment During Sensitive Periods Results in Body Weight Changes Across Generations

Objective : This study asked whether a brief period of over-nutrition during a developmentally sensitive time could impact the individual's adult weight and that of succeeding generations. Research Methods and Procedures : Female rat pups (F₁ generation) were randomly assigned to 1 of 3 groups: (1) a control group that was naturally reared by mothers; (2) another control group implanted with chronic gastric fistulas on postnatal day 4 and fed enough formula to match the growth of the mother-reared group; and (3) an experimental group gastrostomized and infused from day 8 through day 16 with a greater quantity of food than gastrostomy-reared controls (OF). On postnatal day 16, both gastrostomy-reared groups were returned to normal litters. Adult F₁ females from overfed and mother-reared groups were bred with normal males to yield an F₂ generation. F₂ adult females were bred to normal males to produce an F₃ generation. Results : When adult, the F₁ experimental group was heavier than control groups. F₂ adults from OF mothers were smaller than those from the control group. F₃ animals from OF grandmothers were heavier at weaning than F3 descendants from mother-reared animals. Discussion : Excess nourishment during a developmentally sensitive period changed the metabolic phenotype of one generation so dramatically that the gestational development and subsequent phenotype of two succeeding generations were also changed. The experiment models fetal effects of gestational diabetes in humans and may help to elucidate how, independent of genetic anomalies, secular changes can be detected across generations.     

Meiosis in translocation heterozygotes in the mosquito Culex pipiens

Adult Culex pipiens males irradiated with both X-rays and neutrons were crossed to untreated females and F₁-egg rafts were checked for dominant lethality. F₁-progenies were outcrossed with normal individuals in order to obtain lines with inherited semisterility. From a total of 120 lines that showed a certain amount of sterility 12 lines were studied cytologically. 10 lines showed reciprocal chromosome exchanges.—At late pachytene and diplotene cross configurations with large asynaptic regions at the center of the cross are obligatory. Bivalents, chains of three, chains of four, and ring configurations are present at metaphase and anaphase I. The different frequencies of the occurrence of such multiples are dependent on the chromosomes involved in the exchange, the length of the pairing segments and the chiasma frequencies in these segments. Chiasma frequency in the interstitial segments is reduced by means of chiasma interference over the centromere and by asynapsis near the breakage points. — Alternate, adjacent-1- and adjacent-2-distributions are present to a different extent. Alternate distribution is most, adjacent-2-distribution least frequent. — The role of translocations and the probability of their becoming effective in pest eradication programs is discussed.     

Genetic studies of corn (Zea mays L.) anther culture response

Summary Anthers of two maize (Zea mays L.) inbred lines, DBTS (P₁) and B73 (P₂), their F₁, F₂ and first backcross generations — F₁ x DBTS (B₁), and F₁ x B73 (B₂) — were float cultured in YP medium to study the inheritance of corn anther culturability using generation mean analysis. Significant effects of generation were observed for the three traits measured: anther response (%), frequency of embryos (%) and anther productivity. Variation among the generations was similar for anther response and frequency of embryos: no significant differences were found among the P₁, F₁, F₂ and B₁ means, but the means of P₂ and B₂ were significantly lower than those of the other generations. For anther productivity, the F₂ generation tended to have a slightly higher tendency for multiple embryo formation. A simple additive-dominance model was adequate in explaining the inheritance of anther response and frequency of embryos, but digenic epistasis (additive x dominance) was involved in the inheritance of anther productivity. Additive genetic variance was higher than non-additive genetic variance for all the traits; however, only environmental variance was significant. Narrow-sense heritability estimates were 65% and 75% for anther response and frequency of embryos, respectively. Significant inter-plant variation was observed within generations, even for the inbred line DBTS, but isozymic analysis involving five enzyme loci did not reveal any genotypic variability within the inbred lines DBTS and B73.     

Does exposure of male Drosophila melanogaster to acute gamma radiation influence egg to adult development time and longevity of F1–F3 offspring?

Two‐ to three‐day‐old male Drosophila melanogaster flies were irradiated with 1, 2, 4, 6, 8, 10, 20, 25, 30, 40 and 50 Gy doses of gamma radiation. The longevity and rate of development were observed for three successive generations to assess the impact of irradiation. The mean lifespan of irradiated flies was significantly increased at 1, 2 and 8 Gy, while it was vice versa for high doses at 30, 40 and 50 Gy. Paternal irradiation had an impact on F₁ generation, with significantly increased mean longevity at 2 (female), 4, 6, 8 and 10 and decreased mean longevity at 40 and 50 Gy (male and female). Significant increase in the longevity was observed in the F₂ generation of the 8 (male and female) and 10 Gy (male) irradiated groups, while decreased longevity was observed in F₂ female progeny at 40 Gy. In the case of F₃ progeny of irradiated flies, longevity did not show significant difference with the control. Paternal exposure to radiation had a significant impact on the mean egg to adult developmental time of the F₁ generation; it was shortened at 2 Gy and extended at 25, 30, 40 and 50 Gy compared to the control. Mean development time at 30, 40 and 50 Gy was significantly increased in the F₂ generation, while there were no significant changes in the F₃ generation. The present study concludes that the effect of acute gamma irradiation on longevity and “egg to adult” development time of D. melanogaster may persist to following generations.     

Transposition of copia-like nomadic elements can be induced by heat shock

Summary Four males of an isogenic gt w^a Drosophila line were heat shocked and then crossed with isogenic untreated females. The genomic distributions of the elements of five copia-like families were analyzed in the four F₁ flies by the Southern technique and compared with those in the untreated isogenic line. The pattern heterogeneity observed in the F₁ samples shows that extensive rearrangements can be induced by heat shock.Presented at the FEBS Symposium on Genome Organization and Evolution, held in Crete, Greece, September 1–5, 1986     

The genetic control of alkaline phosphatase activity in the duodenum of the mouse

The inheritance of duodenal alkaline phosphatase activity has been studied in two inbred strains of Swiss mice. These two strains consistently maintained a three- to fourfold difference in duodenal phosphatase activity for six generations before the start of the genetic studies. Males of both the high-activity strain (HAS) and the low-activity strain (LAS) were mated to females of the other strain to produce an F₁ generation, members of which were sib-mated to produce an F₂ generation. The frequency distributions of the parental, F₁, and F₂ generations reveal that the activity of the enzyme is under polygenic control. Distribution of activities in the F₂'s derived from HAS grandmothers differs from that of the F₂'s from LAS grandmothers, indicating that a maternally inherited factor, probably contained in the milk of one strain, influences the activity. Heritability estimates based on half-sib correlation coefficients show that additive genetic variance makes up about 50–70% of the total variance of duodenal phosphatase activity in LAS, and approximately 30–45% in HAS. The latter strain is the more variable, both within generations and within litters; its activity is also more strongly enhanced by injection of substrate into the stomach, and is more severely reduced by starvation. Chromatographic analysis of butanol extracts of phosphatase from 11-day-old mice of the two strains reveals that both contain the same two isozymes. HAS does, however, appear to have 6–8 times as much as LAS of an isozymic form of phosphatase having a relatively high phenylphosphate/-glycerophosphate ratio, and only about twice as much of a low PhP/bGP ratio form.Supported by Research Grant GM 03937 from the National Institutes of Health, U.S. Public Health Service.     

The inheritance of radiation induced semi-sterility in Rhodnius prolixus

Eggs from crosses of 40 adult male R. prolixus irradiated with 6K rad -rays with normal females had a mean fertility of 23.9%, only 2 crosses being completely sterile. The 86 F₁ progeny of both sexes, when outcrossed with normal mates, had a mean egg fertility of 12.6%, and 43 of these matings were completely sterile. Twenty-eight F₂ bugs reared from F₁ x normal crosses were mated with normal partners and had a mean fertility of 44.6%, 6 of them being fully fertile, a reversal towards normal fertility. Cytogenetic examination of F₁ F₂ and F₃ males showed that these changes in fertility correlated well with the degree of chromosomal abnormality found. The very high recovery rate of translocations in F₁ generation males can be related to the holocentric chromosomes of these bugs which precludes the formation of dicentric chromosomes which are inviable in monocentric species. In F₁ and F₂ males the majority of translocations were associated as chains of III+I or as chains of IV. Only one bug was found with a ring of IV chromosome association and it is suggested that chromosome morphology, combined with a low chiasma frequency, favours chain association. Most chain multivalents showed linear orientation which may lead to duplication deficiencies and zygotic death. However parallel, indifferent and the more stable convergent modes of chain orientation were also all observed indicating that survival of some translocations in this species may be possible. The survival to the F₂ generation of chromosomal fragments confirmed the holocentric nature of triatomine chromosomes. It is suggested that semi-sterile males would prove more effective than releases of completely sterile males for reducing wild populations of R. prolixus, because of the delayed effects of sterilizing radiation consequent upon the holocentric structure of triatomine chromosomes.     

Cold storage effects on maternal and progeny quality of Gonatocerus ashmeadi Girault (Hymenoptera: Mymaridae)

This study determined the effects of cold storage on the survival, development and reproduction of the mymarid wasp, Gonatocerus ashmeadi Girault (Hymenoptera: Mymaridae). Following storage of the immature parasitoids within host eggs of the glassy-winged sharpshooter, Homalodisca vitripennis (Germar) (Hemiptera: Cicadellidae) under a daily fluctuating temperature for up to 50 d, the quality of the parental and F₁ generations was assessed by examining several reproductive and developmental parameters indicating fitness. Immature wasps were stored for 20 d within the host without reducing their subsequent survival, development or progeny fitness parameters. After 30 d of storage, survival declined, post-storage developmental time was extended, and the fecundity of the adult females decreased. Storage for 40 d severely damaged G. ashmeadi, because it not only yielded a 12% survival rate, 44% female sterility and increased the proportion of progeny males by 155%, but it also reduced parasitism and fecundity by 70% and 73%, respectively. No wasps emerged after 50 d of storage. Cold storage affected the emergence pattern of the parental but not the F₁ and F₂ generations. Parental emergence was extended and the pattern displayed two additional peaks after the initial onset. Analysis of several demographic parameters for the parental and F₁ generations further confirmed that the quality of the adult parents declined after they had been stored as immatures for 30 d. The detrimental effects caused by cold storage of the parental generation do not extend to the F₁ generation. Our results indicate that short-term cold storage of G. ashmeadi within its host could be used for maintaining and accumulating these parasitoids during mass propagation for release in a control program.     

Transovarial Transmission of Orientia tsutsugamushi in Leptotrombidium palpale (Acari: Trombiculidae)

Transovarial transmission of Orientia tsutsugamushi in colonies of Leptotrombidium palpale was studied in the parent and F₁ and F2 generations. Both transovarial transmission and filial infection rates were 100% in the parent and F₁ generations of Leptotrombidium palpale. The filial infection rate in the F₁ generation was 100%, but it declined to 94.3% in the F₂ progeny. The sex ratio of the F₁ generation from infected L. palpale was 1∶0.8 (male:female) and the proportion of males was relatively high. This study is the first to report on the transovarial transmission of O. tsutsugamushi in L. palpale. High transovarial transmission rates in L. palpale suggest that this species might be one of the major vectors of tsutsugamushi disease in Korea.     

Cuticular hydrocarbon gas chromatography analysis of Argas vulgaris,A. polonicus,and their hybrids

The cuticular hydrocarbon gas chromatography of adult ticks obtained from experimental homogamic and reciprocal heterogamic crosses of Argas vulgaris (Vv) and A. polonicus (Pp) confirmed both argasids to be closely related species, but easily differentiated by several critical compounds. Cuticular mixtures contained variable amounts of n-alkanes, monomethyl-, and dimethyl-alkanes, without traces of detectable alkenes. Specimens from heterogamic crosses synthesized new high molecular weight compounds not detected in parental cuticular mixtures. Data on genetic identity revealed a close proximity of parental adults, but a high distances between and within their hybrids. A relatively high percentage of heterozygosity (32.12% in females and 20.00% in males) of F₁ Pv generation in comparison with F₁ Vp (14.54% and 8.48% respectively) and both P₂ generations (6.66–9.09%) has also been ascertained.     

Analysis of complex allozyme polymorphisms in a barley population

Genotypes of 68,230 individuals taken from 10 generations (F₄–F₆, F₁₄–F₁₇, F₂₄–F₂₆) of an experimental population of barley were determined for four esterase loci. The results show that frequencies of gametic ditypes changed significantly over generations and that striking gametic phase disequilibrium developed within a few generations for each of the six pairwise combinations of loci which were monitored. The complex behavior of these four enzyme loci in the population is attributed to interactions between selection and restriction of recombination resulting from the effects of linkage and/or inbreeding.     

The locus Om,responsible for the DDK syndrome,maps close to Sigje on mouse Chromosome 11

The DDK inbred strain of mouse has a striking particularity: when DDK females are crossed to males of other strains they exhibit a reduced fertility, whereas the reciprocal crosses (non-DDK females x DDK males) are fertile (Wakasugi et al. 1967; Wakasugi 1973). The low fertility results from an early embryonic lethality, the F₁ embryos dying near the late morula-early blastocyst stage. Genetic analyses (Wakasugi 1974) and nuclear and cytoplasmic transfers (Renard and Babinet 1986; Babinet et al. 1990; Mann 1986), have shown that the failure of the embryos to develop is due to an incompatibility between a DDK maternally encoded cytoplasmic product and the non-DDK paternal genome. In order to elucidate the genetic determinism of this embryonic lethality, we have analyzed the fertility of male progeny from a backcross BALB/c females x (BALB/c x DDK)F₁ males and that of males from a set of recombinant inbred (RI) strains, established from DDK and BALB/c progenitors, when mated with DDK females. Our results indicate that a single locus, Om, is responsible for the DDK syndrome and is located on Chromosome (Chr) 11, very close to the Sigje locus.     

Safety of a novel oxygen-coordinated niacin-bound chromium(III) complex (NBC): I. Two-generation reproduction toxicity study

The objective of this study was to evaluate the effects of a novel oxygen-coordinated niacin-bound chromium(III) complex (NBC) on the reproductive systems of male and female rats, the postnatal maturation and reproductive capacity of their offspring, and possible cumulative effects through multiple generations. Sprague-Dawley rats were maintained on feed containing NBC at dose levels of 0, 4, 15, or 60 ppm for 10 weeks prior to mating, during mating, and, for females through gestation and lactation, across two generations. For the parents (F₀ and F₁) and the offspring (F₁ and F_2a), reproductive parameters such as fertility and mating, gestation, parturition, litters, lactation, sexual maturity and development of offspring were assessed. Results from the current study indicated that dietary exposure of NBC to parental male and female rats of both (F₀ and F₁) the generations during the premating and mating periods, for both sexes, and during gestation and lactation in case of female rats, did not cause any significant incidence of mortality or abnormal clinical signs. Compared to respective controls, NBC exposure did not affect reproductive performance as evaluated by sexual maturity, fertility and mating, gestation, parturition, litter properties, lactation and development of the offspring. Based on the findings of this study, the parental as well as the offspring no-observed-adverse-effect level for NBC was determined to be greater than 60 ppm in diet or equivalent to 7.80 and 8.31 mg/kg body weight/day in male and female rats, respectively.     

Radiation biology and inherited sterility of light brown apple moth (Lepidoptera: Tortricidae): developing a sterile insect release program

The radiation biology of two geographically isolated populations of the light brown apple moth [Epiphyas postvittana (Walker)] was studied in Australia and New Zealand as an initiation of a SIT/F1 sterility program. Pharate and < or = 2 d pre-emergence pupae were exposed to increasing radiation doses up to a maximum dose of 300 Gy. Fertility and other life history parameters were measured in emerging adults (parental) and their progeny (F1-F3 adults). Parental fecundity was significantly affected by increasing irradiation dose in pharate pupae only. For both populations, parental egg fertility declined with increasing radiation. This was most pronounced for the irradiated parental females whose fertility declined at a higher rate than of irradiated males. At 250 Gy, females < or = 2 d preemergence pupae produced few larvae and no adults at F1. No larvae hatched from 250 Gy-irradiated female pharate pupae. At 300 Gy, males still had residual fertility of 2-5.5%, with pharate pupae being the more radio-sensitive. Radiation-induced deleterious inherited effects in offspring from irradiated males were expressed as increased developmental time in F1 larvae, a reduction in percent F1 female survival, decreased adult emergence and increased cumulative mortality over subsequent generations. Males irradiated at > or = 150 Gy produced few but highly sterile offspring at F1 and mortality was > 99% by F2 egg.     

Optimal mass selection policies for schemes with overlapping generations and restricted inbreeding

Optimum breeding schemes for maximising the rate of genetic progress with a restriction on the rate of inbreeding (per year or per generation) are investigated for populations with overlapping generations undergoing mass selection. The optimisation is for the numbers of males and females to be selected and for their distribution over age classes. Expected rates of genetic progress (ΔG) are combined with expected rates of inbreeding (ΔF) in a linear objective function (Φ = ΔG - λΔF) which is maximised. A simulated annealing algorithm is used to obtain the solutions. The restriction on inbreeding is achieved by increasing the number of parents and, in small schemes with severe restrictions, by increasing the generation interval. In the latter case the optimum strategy for obtaining the maximum genetic gain is far from truncation selection across age classes. In most situations, the optimum mating ratio is one but the differences in genetic gain obtained with different mating ratios are small. Optimisation of schemes when restricting the rate of inbreeding per generation leads to shorter generation intervals than optimisation when restricting the rate of inbreeding per year.