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A case-control study of paternal smoking and birth defects.

Although the influence of paternal smoking on birth defects is of great public interest, epidemiological evidence concerning this potential relationship is extremely limited. A stratified random sample of 29 hospitals in the Shanghai Municipality, China, was used to select 1012 birth defects cases and controls. Mothers of the cases and controls were interviewed in the hospitals from October 1986 to September 1987. A modest relationship between paternal smoking and overall birth defects in offspring was identified [odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.01-1.45]. More markedly elevated risks were identified for anencephalus (OR = 2.1), spina bifida (OR = 1.9), pigmentary anomalies of the skin (OR = 3.3) and varus/valgus deformities of the feet (OR = 1.8). Our analysis also shows that paternal smoking is more likely to be associated with multiple rather than isolated malformations. A paternally-mediated effect of smoking on birth defects is suggested and further studies are encouraged.

Adult↗

Paternity following treatment for testicular cancer.

BACKGROUND: Studies of fertility in men treated for testicular cancer have mainly addressed serum follicle-stimulating hormone levels and sperm parameters. We assessed post-treatment paternity among long-term survivors of testicular cancer. METHODS: Men (n = 1814) who had been treated for unilateral testicular cancer in Norway during 1980 through 1994 were invited to participate in a national multi-center follow-up survey in 1998 through 2002. The participants were allocated to five groups according to the treatment received after orchiectomy, including treatment at relapse (surveillance, retroperitoneal lymph node dissection, radiotherapy, low-dose chemotherapy [i.e., < or = 850 mg cisplatin], and high-dose chemotherapy [i.e., > 850 mg cisplatin]). Cox proportional hazards analysis was used to assess predictive factors for post-treatment paternity. Statistical tests were two-sided. RESULTS: A total of 1433 men were assessable, of whom 827 were fathers at diagnosis. Post-treatment conception was attempted by 554 men, among whom the overall 15-year actuarial post-treatment paternity rate was 71% (95% confidence interval [CI] = 66% to 75%) without the use of cryopreserved semen. This rate ranged from 48% (95% CI = 30% to 69%) in the high-dose chemotherapy group to 92% (95% CI = 78% to 98%) in the surveillance group (P < .001). The median actuarial time from diagnosis to the birth of the first child after treatment was 6.6 years overall but varied according to treatment. Assisted reproductive technologies were used by 22% of the couples who attempted conception after treatment. Dry ejaculation, treatment group, pretreatment fatherhood, and marital status were statistically significant independent predictors for post-treatment fatherhood, with dry ejaculation as the most important negative factor. CONCLUSIONS: Although the overall paternity rate after treatment for testicular cancer was high, the ability to conceive and the time to conception reflected the intensity of treatment. These data may help inform patients about their future ability to father biological children.

Actuarial Analysis↗

High-resolution phylogenetic analysis of southeastern Europe traces major episodes of paternal gene flow among Slavic populations.

The extent and nature of southeastern Europe (SEE) paternal genetic contribution to the European genetic landscape were explored based on a high-resolution Y chromosome analysis involving 681 males from seven populations in the region. Paternal lineages present in SEE were compared with previously published data from 81 western Eurasian populations and 5,017 Y chromosome samples. The finding that five major haplogroups (E3b1, I1b* (xM26), J2, R1a, and R1b) comprise more than 70% of SEE total genetic variation is consistent with the typical European Y chromosome gene pool. However, distribution of major Y chromosomal lineages and estimated expansion signals clarify the specific role of this region in structuring of European, and particularly Slavic, paternal genetic heritage. Contemporary Slavic paternal gene pool, mostly characterized by the predominance of R1a and I1b* (xM26) and scarcity of E3b1 lineages, is a result of two major prehistoric gene flows with opposite directions: the post-Last Glacial Maximum R1a expansion from east to west, the Younger Dryas-Holocene I1b* (xM26) diffusion out of SEE in addition to subsequent R1a and I1b* (xM26) putative gene flows between eastern Europe and SEE, and a rather weak extent of E3b1 diffusion toward regions nowadays occupied by Slavic-speaking populations.

Male↗

Association of childhood leukemia with maternal age, birth order, and paternal occupation. A case-control study.

Previous investigations have drawn conflicting conclusions concerning the association between childhood leukemia and maternal age, birth order, socioeconomic status, and paternal occupation. In this study, 255 childhood leukemia cases diagnosed in California between 1975 and 1980 were individually matched with two living controls on the basis of sex, date of birth, and county of birth. Data were derived from subjects' birth certificates. Socioeconomic status and paternal benzene exposure were determined from the paternal occupation stated on the birth certificate. Hispanics and males were overrepresented in the case group. Cases were also less likely to be of birth order one. No difference was found between case and control groups for maternal age or paternal occupation. Analyses with stratification on age, sex, and leukemia cell type are reported.

Adolescent↗

Paternal factors and schizophrenia risk: de novo mutations and imprinting.

There is a strong genetic component for schizophrenia risk, but it is unclear how the illness is maintained in the population given the significantly reduced fertility of those with the disorder. One possibility is that new mutations occur in schizophrenia vulnerability genes. If so, then those with schizophrenia may have older fathers, because advancing paternal age is the major source of new mutations in humans. This review describes several neurodevelopmental disorders that have been associated with de novo mutations in the paternal germ line and reviews data linking increased schizophrenia risk with older fathers. Several genetic mechanisms that could explain this association are proposed, including paternal germ line mutations, trinucleotide repeat expansions, and alterations in genetic imprinting in one or several genes involved in neurodevelopment. Animal models may be useful in exploring these and other explanations for the paternal age effect and they may provide a novel approach for gene identification. Finally, it is proposed that environmental exposures of the father, as well as those of the mother and developing fetus, may be relevant to the etiology of schizophrenia.

Fathers↗

Association between sweet preference and paternal history of alcoholism in psychiatric and substance abuse patients.

BACKGROUND: The relationship between preference for stronger sweet solutions and propensity to excessive alcohol drinking is supported by both animal and human studies. This study was designed to test the hypothesis that sweet preference is associated with the genetic risk of alcoholism as measured by a paternal history of alcoholism. METHODS: Participants were 180 patients admitted to a residential treatment program for the treatment of alcoholism, drug dependence, or psychiatric conditions. In addition to a routine medical examination, patients completed the standard sweet preference test twice (on the 9th and 24th days after admission), and the family history of alcoholism was evaluated. RESULTS: Sweet preference was shown to be stable over time. It was strongly associated with a paternal history of alcoholism, with family history-positive patients approximately 5 times more likely to prefer stronger sweet solutions than family history-negative subjects. Such factors as dependence on alcohol, cocaine, opiates, cannabis, other drugs (including prescription drugs), and tobacco smoking, as well as demographics (gender and age), did not significantly interfere with association between sweet preference and paternal history of alcoholism. CONCLUSIONS: These findings provide some support for the hypothesis that preference for stronger sweet solutions is associated with a genetic predisposition to alcoholism as measured by a paternal history of alcoholism.

Adult↗

Molecular analysis of paternity shows promiscuous mating in female humpback whales (Megaptera novaeangliae, Borowski).

It is widely assumed that the mating system of the humpback whale. Magaptera novaeangliae, is similar to that of most mammals in that it represents some form of polygyny or promiscuity, but this cannot be tested without observations of copulation or data on paternity of offspring. Microsatellite DNA markers were used to examine the paternity of calves born to individually identified mature female humpback whales from the Gulf of Maine. Skin biopsies were obtained from three females, and several (range: three to five) of their known offspring. Multiple paternity of offspring, indicated by the presence of at least three different paternal alleles, was evident in all three females at either three or four of the six microsatellite loci surveyed. Such promiscuous mating is expected given current knowledge of the social ecology of this species. It is also consistent with resightings of individually identified female humpbacks with different male associates during two or more breeding seasons.

Animals↗

Pectoral fins and paternal quality in sticklebacks.

Sexual selection through female mate choice exerts a strong selection pressure on males' sexual traits, particularly when direct benefits are involved. In species with male parental care, one would expect sexual selection to favour paternal quality, for instance through selection on morphological structures which promote quality. We experimentally studied the influence of pectoral fins on paternal quality in male three-spined sticklebacks (Gasterosteus aculeatus L.). After reductions of fin area to different degrees, similar-sized males had to perform a complete reproductive cycle in enclosures in the field. The collected data on fanning behaviour and egg development showed that a reduction in pectoral fin size affected paternal quality probably through an increased beat frequency of the pectorals. Thus, pectoral fins can potentially signal paternal quality to choosy females.

Animals↗

Female control of paternity in the sexually cannibalistic spider Argiope keyserlingi.

Sexual conflict theory predicts an antagonistic coevolution, with each sex evolving adaptations and counter-adaptations to overcome a temporary dominance of the other sex over the control of paternity. Polyandry allows sexual selection to operate after mating has commenced, with male and female interests competing for control of fertilization. There are numerous examples of male control of paternity, but few studies have unambiguously revealed female control. Attributing variance in paternity to females is often difficult since male and female influences cannot be separated unambiguously. However, we show that polyandrous female orb-web spiders Argiope keserlingi (Arancidae) control the paternity of their offspring by adjusting the timing of sexual cannibalism. Our experiments reveal that females copulating with relatively smaller males delay sexual cannibalism, thereby prolonging the duration of copulation, and that these males consequently fertilize relatively more eggs.

Animals↗

Dynamic adjustment of parental care in response to perceived paternity.

Theories of parental care evolution predict that genetic relatedness will be an important variable in the amount of care a parent provides. However, current inferences of relatedness-based parental investment from studies in humans and birds remain challenged. No study has yet demonstrated parental care adjustment in a manner uncomplicated by life-history correlates or experimental design. We now present a unique test that controls for individual life histories and demonstrates paternity-related dynamic adjustments in parental care. Brood-rearing male bluegill sunfish (Lepomis macrochirus) that are cuckolded to a varying degree will either increase or decrease their parental investment in response to changing information on paternity during brood development. Specifically, as parental males detect paternity lost to cuckolders and, hence, a reduction in the value of their brood, they adaptively lower their level of parental care. Conversely, if they detect that their paternity is higher than previously assessed, they adaptively raise their level of parental care. This dynamic adjustment during brood rearing indicates the importance of genetic relatedness in parental investment decisions and provides needed empirical support for theoretical predictions.

Animals↗

Limiting dilution analysis of the allo-MHC anti-paternal cytotoxic T cell response. I: Normal primigravid and multiparous pregnancies.

Anti-paternal cytotoxic T lymphocyte precursor frequencies (CTLpF) were determined by limiting dilution analysis (LDA) in the peripheral blood of eight primigravid and seven multiparous women during the three trimesters of pregnancy. In five of these women the responses to cord blood lymphocytes (CBL) and paternal lymphocytes were also determined at the time of delivery and at 6 weeks post delivery. As controls, CTLpF against unrelated third party donors were determined. A wide range of CTLpF against all three groups of targets was found in both the primigravid and multiparous women, reflecting the wide range of frequencies found in random populations. These frequencies remained fairly constant during and 6 weeks after the pregnancy. Splitwell analysis demonstrated that the responses generated in our culture system were specific to the stimulator. The LDA data conform to single-hit kinetics, indicating that only cytotoxic T cells were limiting in the assay. Proliferative responses of maternal lymphocytes to paternal, cord blood and third party MHC antigens also remained unchanged as determined by time-course mixed lymphocyte reactions (MLR). Our data suggest that there is no significant allo-stimulation or suppression of the maternal immune system during normal pregnancy. The mother remains immunocompetent and is capable of both cytotoxic and proliferative responses to paternally-derived fetal MHC antigens. Our findings confirm that in normal pregnancy the trophoblast, which is devoid of classical MHC antigens, forms an effective immune barrier which prevents interaction of the maternal and fetal immune systems.

Cells, Cultured↗

The effect of paternal heat stress on protein profiles of pre-implantation embryos in the mouse.

The study was undertaken to compare the protein profiles of [35S]-methionine-labelled control-sired embryos with heat-sired embryos at 7, 14 or 21 days after mature fertile B6CBF F1 male mice were kept at 36 +/- 0.3 degrees C and 62 +/- 2.7% relative humidity for 24 h. One-dimensional gel electrophoresis and autoradiographs were used to examine the protein profiles between the two-cell embryos and the blastocysts. The results obtained demonstrate that paternal heat stress 7 or 14 days earlier did not apparently affect protein patterns of two-cell embryos, four-cell to eight-cell embryos, morulae or blastocysts. However, 21 days earlier, there were changes in protein patterns of two-cell embryos and abnormal embryos, but not the morulae. To further support and extend these results, two-dimensional gel electrophoresis and phosphorimaging were employed and the results obtained show that paternal heat stress 21 days before mating affected protein profiles of two-cell embryos and morulae in the mouse. Together, these findings have indicated that paternal heat stress affects most but not all protein patterns of pre-implantation embryos, which strongly supports our previous results demonstrating that paternal heat stress significantly reduced the developmental proportion of pre-implantation embryos in the mouse.

Animals↗

Increased selfing and correlated paternity in a small population of a predominantly outcrossing conifer, Pinus sylvestris.

Outcrossing rate, the rates of ovule and seed abortion, and levels of correlated paternity were estimated in a small population of Pinus sylvestris, a predominantly outcrossing conifer, and were compared with estimates from two widely dispersed woodlands of the same species, showing a range of densities. On average, seed trees of the small population showed an eight-fold higher selfing rate (25 vs. 3%) and a 100-fold greater incidence of correlated paternity (19.6 vs. 0.2%) than did trees from the large populations. No evidence was found of pollen limitation within the remnant stand, as suggested by ovule abortion rates. Investigation of the mating patterns in the small population, based on the unambiguous genealogy of 778 open-pollinated seeds, showed a large departure from random mating. Only 8% of the possible mating pairs within the stand were observed. Correlated paternity rate within a maternal sibship was negatively associated (rs = -0.398, P < 0.050) with the distance to the nearest neighbour, and shared paternity among maternal sibships was negatively correlated (rs = -0.704, P < 0.001) with the distance between seed trees. Numerical simulations, based on the estimated individual pollen dispersal kernel, suggest that restricted dispersal might have been the key factor affecting mating patterns in the small population and, together with low population density, may account for the observed mating system variation between the small and the large populations. The results of this study show that a severe size reduction may substantially affect the mating system of a wind-pollinated, typically outcrossed plant species.

Computer Simulation↗

A tale of two siblings: multiple paternity in big brown bats (Eptesicus fuscus) demonstrated using microsatellite markers.

In many bat species, the opportunity for sperm competition or other mechanisms of post-copulatory paternity biasing is thought to be great, due to the long delay between copulation and fertilization, demonstrated sperm storage capabilities, and observed promiscuity. We present the results of the first study to assess whether litters of big brown bats (Eptesicus fuscus) containing dizygotic twins share the same father. We sampled 26 mother-offspring triads from three colonies in Indiana and Illinois, as well as 299 additional adults (237 females and 62 males) from these colonies and six other maternity colonies in the same area in 1997-1998. All individuals were genotyped at nine highly variable autosomal microsatellite loci and one X-linked locus. We assessed multiple paternity using autosomal and X-linked locus exclusions, and using maximum-likelihood methods. All methods confirmed multiple paternity within litters, and the maximum-likelihood analyses indicated that almost half of the sampled litters were composed of maternal half-siblings rather than full-siblings. Our results highlight the potential importance of post-copulatory mechanisms of paternity determination in the mating system of big brown bats, and have important implications for gene flow and population structuring in this species.

Animals↗

Finding fathers: spatio-temporal analysis of paternity assignment in grey seals (Halichoerus grypus).

Molecular studies of pinniped breeding systems exhibit a broad range of agreement and disagreement with observational indices of male breeding success. Grey seal studies have reported considerable discrepancies between genetic and behavioural paternity measures that have been interpreted as evidence of previously unidentified male strategies and/or tactics. Therefore, these studies have the power to fundamentally alter our perceptions of mating systems. However, other pinniped studies exhibit no such disagreements, and one possible explanation for disparities may be sampling biases in space and time. Therefore, it is essential that potential sampling biases are examined to evaluate the likelihood of previously unidentified male strategies. We examined paternities assigned at the North Rona grey seal colony between 1999 and 2002 in relation to concurrent detailed behavioural and locational data for males and females. We found that (i) for females observed in sexual interaction(s) during their oestrus period, it was highly probable that one of the interacting males fathered their next pup; (ii) over 80% of assigned paternities agreed with observations of the in-colony behaviour and spatio-temporal proximity of the males and females involved; and (iii) a minority of females exhibit mate choice and seek sires outside their local male's home range, although evidence suggests that these females mate on the colony rather than at sea. In conclusion, nearly all paternities assigned agreed with expectation based upon detailed knowledge of the spatio-temporal patterns of individuals during the breeding season. We found little evidence of unidentified male strategies at North Rona, Scotland, whereas further examination of mechanisms of female choice may be productive.

Animals↗

How female reed buntings benefit from extra-pair mating behaviour: testing hypotheses through patterns of paternity in sequential broods.

Extra-pair paternity is an important aspect of reproductive strategies in many species of birds. Given that in most species females control whether fertilization occurs, they are expected to benefit in some way from the extra-pair matings. In this study we use patterns of extra-pair paternity (EPP) in broods of individual reed buntings (Emberiza schoeniclus), both within and between seasons, to test four hypothesized female benefits: (1) assessing potential future partners and seeking (2) genetic diversity (3) good genes, or (4) compatible genes. Reed buntings are socially monogamous, multibrooded passerines with extremely high levels of extra-pair paternity. We studied a population of reed buntings in the Netherlands in 2002 and 2003; 51% of offspring in 74% of nests were extra-pair. We showed that patterns of EPP did not support the first and second hypotheses, since females did not form a pair with previous extra-pair partners, EPP was not evenly distributed among broods and more broods than expected were sired by a single male. Furthermore, there was no relation between a male's within- and extra-pair fertilization success, no consistency in EPP between breeding attempts, no effect of parental relatedness on EPP and several cases of reciprocal paternity. These patterns do not support the good genes hypothesis and are most consistent with the genetic compatibility hypothesis. However, our previous finding that older males are more successful in gaining EPP, suggests some effect of good genes. These hypotheses need not be mutually exclusive, as females may select compatible males above a certain quality threshold (e.g. old males).

Animals↗

Paternal inheritance of the primary sex ratio in a copepod.

Uniparentally inherited genetic elements are under strong selection to manipulate sex determination in their host and shift the host sex ratio towards the transmitting sex. For any sex-ratio trait, lineage analysis and quantitative genetics are important tools for characterizing the mode of inheritance (biparental vs. maternal vs. paternal) thereby narrowing the field of possible sex-determining mechanisms (e.g. polygenic, sex chromosomes with meiotic drive, cytoplasmic microorganisms). The primary sex ratio of the harpacticoid copepod, Tigriopus californicus is often male-biased and is highly variable among full sib families. We found that this extra-binomial variation for the primary sex ratio is paternally but not maternally transmitted in T. californicus. Paternal transmission of the primary sex ratio has been well documented in the haplo-diploid hymenoptera but is relatively rare in diplo-diploid organisms. If the sex-ratio trait is paternally transmitted in other closely related harpacticoid copepods it would explain why male biased primary sex ratios are so common in this group.

Animals↗

Effect of paternal heat stress on the development in vitro of preimplantation embryos in the mouse.

This study was conducted to investigate the effects of paternal heat stress on the development in vitro of preimplantation embryos in the mouse. Female C57/CBA mice were superovulated using eCG/hCG and mated either to an untreated (control) male mouse or to one that had been exposed for 24 h to an ambient temperature of 36 +/- 0.1 degrees C and 62 +/- 0.4% relative humidity, between 3 and 42 days previously. Putative zygotes were collected from the oviducts of mated mice, 25-28 h after hCG injection, and cultured in vitro. Embryo development was evaluated at 24-h intervals for up to 120 h. Paternal heat stress significantly reduced the proportion of embryos that developed normally during 24-120 h of in vitro culture, when zygotes were sired by males which had been heat stressed between 7 and 35 days prior to mating. Maximum impairment to development (including nondevelopment, abnormal and dying/dead embryos) occurred in those embryos sired by males at days 14 and 21 after heating. Embryo development returned to control levels by day 42 after heat stress. Furthermore, whilst all stages of embryo development were affected by paternal heat stress, the proportion of embryos at the two-cell stage appeared to be most severely affected. Four-cell to morula stages and the morula to blastocyst stage also demonstrated impairment at days 14, 21, 28 and 35 after heating. These results demonstrate that a single episode of paternal heat stress significantly reduces the development of preimplantation embryos, and this is not recovered until day 42 after heating. The present results also support previous work demonstrating that sperm from the epididymis as well as germ cells in the testis are susceptible to damage by heat stress, with both spermatids and spermatocytes being the most vulnerable.

Animals↗