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PubMed1986

Reports of paternal alcoholism: reliability across siblings.

Recent studies of the correlates of having an alcoholic relative have relied heavily upon study participants' reports of the drinking behavior of their parents and other near relatives. These investigations have rarely attempted to validate the reports of familial alcohol problems or report on the reliability of information across other family members. The present study examined the reliability of reports of parental drinking behavior in a sample of 88 sibling pairs on versions of the Short Michigan Alcoholism Screening Test adapted so that subjects endorsed items pertaining to their father's (F-SMAST) or mother's (M-SMAST) drinking behavior. Because of the relative infrequency of offspring reports of maternal problem drinking in this sample, only data from the F-SMAST were suited for analysis. Siblings' reports of specific paternal drinking consequences showed relatively low agreement on items requiring inference (e.g., the presence or absence of guilt) and relatively high agreement on items referring to specific behavioral acts or consequences (e.g., seeking help, being arrested, driving under the influence). Global judgments of paternal alcoholism and overall scores on the F-SMAST showed adequate levels of reliability. It is concluded that, although it is always desirable to validate offsprings' reports of relatives' drinking, such reports tend to agree with those of other siblings, and the use of these reports is reasonable when validation is impossible or unfeasible.

Adult↗
PubMed1982

The effect of paternal alcohol consumption on fetal development in mice.

The purpose of this study was to evaluate the effect of chronic paternal alcohol consumption on fetal growth and development in C3H mice. Male mice were pair-fed isocaloric liquid diets containing either 30%, 20%, or 0% ethanol-derived calories, or given free access to lab chow. After four weeks of treatment, all males were allowed to mate with untreated females. No differences were found between the litters of alcohol-treated males and controls in terms of the number of implantation sites, prenatal mortality, fetal weight, sex ratio, or frequency of soft tissue malformations. The results suggest that paternal alcohol consumption does not grossly alter fetal growth and development in C3H mice.

Abnormalities, Drug-Induced↗
PubMed1993

Methods and concepts in detecting abnormal reproductive outcomes of paternal origin.

There is conclusive evidence that exposures of human males to ionizing radiation or certain chemicals can diminish sperm production and reduce fertility. Of approximately 100 chemical agents and mixtures that have been evaluated in men by semen analysis, about half (mostly drugs and a few occupational exposures) reduced sperm quantity and quality; several of these agents also affected the fertility of exposed men. It is now well recognized that the importance of the father in reproduction goes beyond fertilization. Abnormalities in paternal chromosomes (structural and numeric) have been found in various abnormal reproductive outcomes, including chromosomal abnormality syndromes among newborns. In rodent systems, exposure of males to mutagens before mating induces transmissible cytogenetic and genetic abnormalities as well as morphologic defects and cancer among offspring. Consistent with animal findings, there is growing epidemiologic evidence of associations between male exposures to exogenous agents and abnormal reproductive outcomes (fetal loss, birth defects, childhood cancer, etc.). However, no clear links have been established between exposure, mechanism of transmission, and abnormal reproductive outcomes. It is not known to what extent male-mediated birth defects and childhood cancer are due to genetic, epigenetic, or nongenetic causes. Viewed in a multigenerational context, the role of the father in abnormal reproductive outcomes is dependent on his exposure history and susceptibilities as well as those of his mate. Relevant exposures may occur any time between conception of the parents and production of their fertilizing gametes, including their development in utero, childhood, and adolescence. Efficient measurements (including biomarkers) of relevant exposure, early biologic effects, and susceptibility in human males are under development. An integrated approach is recommended for assessing male reproductive and genetic toxicity that utilizes biomarkers in (a) epidemiologic studies of exposed human populations, (b) risk characterization in sensitive laboratory species, and (c) in vivo and in vitro studies of the molecular mechanisms of action of toxicants. A special category of "bridging" biomarkers is needed for evaluating animal data for risk assessment and for discriminating among genetic, epigenetic, and nongenetic mechanisms of abnormal reproductive outcomes of paternal origin.

Adult↗
PubMed2004

Independent origins of Indian caste and tribal paternal lineages.

The origins of the nearly one billion people inhabiting the Indian subcontinent and following the customs of the Hindu caste system are controversial: are they largely derived from Indian local populations (i.e. tribal groups) or from recent immigrants to India? Archaeological and linguistic evidence support the latter hypothesis, whereas recent genetic data seem to favor the former hypothesis. Here, we analyze the most extensive dataset of Indian caste and tribal Y chromosomes to date. We find that caste and tribal groups differ significantly in their haplogroup frequency distributions; caste groups are homogeneous for Y chromosome variation and more closely related to each other and to central Asian groups than to Indian tribal or any other Eurasian groups. We conclude that paternal lineages of Indian caste groups are primarily descended from Indo-European speakers who migrated from central Asia approximately 3,500 years ago. Conversely, paternal lineages of tribal groups are predominantly derived from the original Indian gene pool. We also provide evidence for bidirectional male gene flow between caste and tribal groups. In comparison, caste and tribal groups are homogeneous with respect to mitochondrial DNA variation, which may reflect the sociocultural characteristics of the Indian caste society.

Analysis of Variance↗
PubMed2007

Paternal indirect genetic effects on offspring viability and the benefits of polyandry.

Although females are expected to maximize their reproductive success with only one or a few matings, the females of many species mate with multiple partners. Experimental studies have found evidence for an increase in egg or embryo viability when females mate polyandrously. These studies have been interpreted in the context of genetic-benefit models that propose that multiple mating increases offspring viability because it allows females to select male genotypes that influence viability directly or because it allows females to avoid genetic incompatibility. However, no studies have examined directly the precise mechanisms by which parents influence embryo viability. Using a morphological marker that enabled us to determine paternity and survival of embryos sired by individual male crickets in both sperm-competitive and -noncompetitive situations, we show that males inducing high embryo viability enhance the viability of embryos sired by inferior males. These results indicate that paternal effects and interacting phenotypes determine embryo viability. They show that a male's reproductive success is modified by the interaction between indirect genetic effects of sperm competitors. Importantly, our findings show that the benefits accruing to offspring of multiply mated females need not be transmitted genetically.

Animals↗
PubMed2005

Exclusive paternal expression and novel alternatively spliced variants of epsilon-sarcoglycan mRNA in mouse brain.

Mutations of SGCE encoding epsilon-sarcoglycan cause myoclonus-dystonia. SGCE is paternally expressed; however, 5-10% of patients show maternal inheritance of the disease. We found Sgce was exclusively paternally expressed in mice by using a novel polymorphism marker. The result was confirmed in Sgce heterozygous knockout mice. This finding suggests that maternally inherited myoclonus-dystonia may not result from maternal expression of SGCE. Furthermore, we report a new family of alternatively spliced Sgce mRNA expressed in the brain coding for different C-terminal sequences possessing a PDZ-binding motif. Our results provide a better basis for diagnosis and understanding of the pathogenesis of myoclonus-dystonia.

Alternative Splicing↗
PubMed2006

Partial trisomy 1p due to paternal t(1;9) translocation in a family with recurrent miscarriages.

OBJECTIVE: To report a new case with partial trisomy 1p due to paternal t(1;9) translocation in a family with recurrent miscarriages. DESIGN: Case report. SETTING: Faculty of Medicine, Cukurova University. PATIENT(S): A couple with recurrent miscarriages, an abnormal fetus, a newborn infant, paternal grandfather and grandmother. INTERVENTION(S): Chorionic villi sampling (CVS), amniocentesis, lymphocytic karyotype, and genetic counseling. MAIN OUTCOME MEASURE(S): Chromosomal analysis of CVS, amniotic cells, and peripheral blood lymphocytes were performed according to standard cytogenetic methods using G-banding technique. RESULT(S): We determined the reproductive risk in a couple who carried a balance and an unbalanced rearrangement of chromosomes 1 and 9 in two generations of a normal father with derivative 9 karyotype. The prenatal and postnatal karyotypes of the newborn infant were the same as the father [46,XY,der(9)t(1:9)(p34.2;q34.3)]. He was also phenotypically normal. The abnormal fetus that was miscarried also had a derivative 9 [46,XY,der(9)t(1:9)(p34.2;q34.3)fat]. The der(9) contained the partial short arm of chromosome 1. Both chromosome 1 showed normal. Trisomy 1p in the fetus was the result of familial derivative 9. CONCLUSION(S): Partial trisomy is associated with fetal wastage, and may play a role in the etiology of the other miscarriages in certain families. The apparent lack of increased reproductive failure may result from the selective disadvantage of aneusomic gamets at fertilization or very early spontaneous abortions of unbalanced conceptuses. The detection of couples with chromosomal anomalies can undoubtedly help prevent the births of malformed infants. These findings would be used widely in clinical genetics and as an effective tool for genetic counseling and reproductive guidance.

Abortion, Habitual↗
PubMed2005

Paternal and sibling incest: a case report.

A case is reported of a female victim of paternal incest, who had also been raped repeatedly by her elder brother for two years. A survey of the literature showed no other report of such a case from Turkey. This does not necessarily mean that the incidence of paternal and sibling incest does not happen, but may indicate that incestuous abuse is not reported or handled without making it known to legal authorities. The victim was first raped by her 16 year-old brother when she was 9 years old. He raped her repeatedly over a period of two years, until he left home. Her father began raping the victim when she was 13 year-old, leaving her pregnant at age 15. He took her to a doctor for a termination of pregnancy. The father continued abuse after the termination. The victim left home to marry a man. The father filed a lawsuit against the man for taking the victim away from home. More openness and awareness of incest in Turkey may encourage the victims to seek help from medical and legal authorities.

Adolescent↗
PubMed2006

Does paternal antigen-induced secretion of interleukin-10 by T regulatory cells mediate the birth order effect?

Childhood allergy constitutes a significant burden of disease in the Western world. The prevalence of this condition is highest in first born children, an as yet unresolved phenomenon called the "birth order effect". The hygiene hypothesis attempted to explain this differential risk by stating that less exposure to microbial agents at an early age of first born children would result in reduced activation of the immune system and subsequent polarization towards a Th2 phenotype. However, no conclusive evidence for or against the hygiene hypothesis has been found so far. Another, not necessarily conflicting, theory states that the birth order effect is already established during prenatal life and that the fetal-maternal interaction changes during successive pregnancies. Combining this theory with research on preeclampsia, another disease originating in pregnancy and also related to birth order, could suggest clues about the mechanisms underlying the birth order effect. Recent research on preeclampsia showed that preeclamptic women have higher levels of pro-inflammatory IL-6 and lower paternal antigen-induced secretion of IL-10 compared to normal pregnant women, indicating a lower number or lower functional activity of T regulatory (Treg) cells. These Treg cells play an important role in maintaining tolerance to fetal antigens in pregnancy and they are found in high numbers at the maternal-fetal interface. We hypothesize that nulliparous women have a lower activity of Treg cells specific to paternal antigens compared to parous women, either in peripheral blood or in the decidua (maternal part of the fetal-maternal interface). If this hypothesis is true, this would mean that the allergen suppressor mechanism of Treg cells is sub-optimal in first born children. This would explain at least a part of the mechanism of the birth order effect and would give us directions for developing preventive measures to prevent possibly 30% of future childhood allergies.

Antigens↗
PubMed2005

APeg3, a novel paternally expressed gene 3 antisense RNA transcript specifically expressed in vasopressinergic magnocellular neurons in the rat supraoptic nucleus.

Vasopressin (VP) and oxytocin (OT) play critical roles in the regulation of salt and water balance, lactation, and various behaviors and are expressed at very high levels in specific magnocellular neurons (MCNs) in the hypothalamo-neurohypophysial system (HNS). In addition to the cell-specific expression of the VP and OT genes in these cells, there are other transcripts that are preferentially expressed in the VP or OT MCNs. One such gene, paternally expressed gene 3 (Peg3), is an imprinted gene expressed exclusively from the paternal allele that encodes a Kruppel-type zinc finger-containing protein involved in maternal behavior and is abundantly expressed in the VP-MCNs. We report here the robust expression in the VP-MCNs of an RNA, which we designate APeg3 that is transcribed in the antisense direction to the 3' untranslated region of the Peg3 gene. The APeg3 mRNA is about 1 kb in size, and the full-length sequence of APeg3, as determined by 5' and 3' RACE, contains an open reading frame that predicts a protein of 93 amino acids and is predominantly expressed in VP-MCNs. Both Peg3 and APeg3 gene expression in the VP-MCNs increase during systemic hyperosmolality in vivo, demonstrating that both of these genes are osmoregulated.

3' Untranslated Regions↗
PubMed2004

Regulation of the paternal inheritance of centrosomes in starfish zygotes.

In most animals, fertilized eggs inherit one centrosome from a meiosis-II spindle of oocytes and another centrosome from the sperm. However, since first proposed by Boveri [Sitzungsber. Ges. Morph. Phys. Münch. 3 (1887) 151-164] at the turn of the last century, it has been believed that only the paternal (sperm) centrosome provides the division poles for mitosis in animal zygotes. This uniparental (paternal) inheritance of centrosomes is logically based on the premise that the maternal (egg) centrosome is lost before the onset of the first mitosis. For the processes of the selective loss of the maternal centrosome, three models have been proposed: One stresses the intrinsic factors within the centrosome itself; the other two emphasize external factors such as cytoplasmic conditions or the sperm centrosome. In the present study, we have examined the validity of one of the models in which the sperm centrosome overwhelms the maternal centrosomes. Because centrosomes cast off into both the first and the second polar bodies (PB) are known to retain the capacity for reproduction and cell-division pole formation, we observed the behavior of those PB centrosomes with reproductive capacity and the sperm centrosome in the same zygotic cytoplasm. We prepared two kinds of fertilized eggs that contain reproductive maternal centrosomes, (1) by micromanipulative transplantation of the PB centrosomes into fertilized eggs, and (2) by suppression of the PB extrusions of fertilized eggs with cytochalasin B. In both types of eggs, the PB centrosomes could double and form cell-division poles, indicating that they are not suppressed by the sperm centrosome, which in turn indicates that selective loss of the maternal centrosome is due to intrinsic factors within the centrosomes themselves.

Animals↗
PubMed2006

Transmission of modified nucleosomes from the mouse male germline to the zygote and subsequent remodeling of paternal chromatin.

Rapidly after gamete fusion, the sperm nucleus loses its specific chromatin conformation and the DNA is repopulated with maternally derived nucleosomes. We evaluated the nature of paternally derived nucleosomes and the dynamics of sperm chromatin remodeling in the zygote directly after gamete fusion. We observed histone H4 acetylated at K8 or K12 already prior to full decondensation of the sperm nucleus, suggesting that these marks are transmitted by the spermatozoon. Tracking down the origin of H4K8ac and H4K12ac during spermiogenesis revealed the retention of nucleosomes with these modifications in the chromocenter of elongating spermatids. We show that sperm constitutive heterochromatin is enriched for nucleosomes carrying specific histone modifications which are transmitted to the zygote. Our results suggest an epigenetic mechanism for inheritance of chromosomal architecture. Furthermore, up to pronucleus formation, histone acetylation and phosphorylation build up in a cascade-like fashion in the paternal chromatin. After formation of the pronucleus, a subset of these marks is removed from the heterochromatin, which suggests a reestablishment of the euchromatin-heterochromatin partition.

Acetylation↗
PubMed2006

Phylogenetic relationships among the baleen whales based on maternally and paternally inherited characters.

Phylogenetic relationships in the Cetacean suborder Mysticeti (baleen whales) have recently been the focus of increased attention. Here, we examine the evolutionary history of this group by comparing genealogies derived from Y chromosome and mitochondrial DNA sequences. We generated topologies based on paternally and maternally inherited characters for males from nine baleen whale species, including representatives of three families (Balaenidae, Eschrichtiidae, and Balaenopteridae) and four genera (Balaena, Eschrichtius, Balaenoptera, and Megaptera). Divergence among species was fifteen times greater for mtDNA than for Y-specific DNA. Both mtDNA and yDNA topologies revealed the family Balaenopteridae to be paraphyletic, but this relationship was neither strongly supported nor consistent across phylogenetic analysis methodologies. Humpback and fin whales, representing different genera, were reciprocally monophyletic sister species according to mtDNA. Although the monophyly of fin whales decayed for yDNA, a close relationship between fin and humpback whales was retained in yDNA trees. The paraphyly of fin whales and the long branch leading to humpback whales for the yDNA marker may suggest life history differences between these species. Specifically, male humpback whales showed higher than average divergence from other baleen whales at yDNA, although not at mtDNA, suggesting a potential for smaller effective population sizes among male humpbacks on an evolutionary timescale. The observation that those species that have been found to hybridize in nature (blue/fin and blue/humpback) do not reveal evidence for paraphyly for either maternal or paternal markers suggests that introgressive hybridization has not historically been extensive and thus may not represent a substantial source of phylogenetic error for Mysticeti.

Animals↗
PubMed1993

Flow cytometric crossmatch and early pregnancy loss in women with a history of recurrent spontaneous abortions who underwent paternal leukocyte immunotherapy.

OBJECTIVE: The purpose of our study was to evaluate the clinical significance of flow cytometric crossmatch in managing women with unexplained recurrent spontaneous abortions who have been immunized with paternal leukocytes. STUDY DESIGN: Two-color flow cytometric crossmatch was performed after immunotherapy in 69 women with recurrent spontaneous abortions to detect maternal immunoglobulin G antibodies against paternal T lymphocytes. A positive flow cytometric crossmatch was determined by a > or = 20 channel increases (256 channel linear scale-log amplification) in the fluorescence intensity of the T-cell peak. We analyzed the clinical correlation between flow cytometric crossmatch results and subsequent pregnancy outcome in those patients using the Fisher exact test. RESULTS: In 46 subsequent pregnancies among 69 immunized women the incidence of early subsequent pregnancy wastage was only 6 (17.1%) of 35 in flow cytometric crossmatch-positive patients and 7 (63.6%) of 11 in flow cytometric crossmatch-negative patients (p < 0.01). CONCLUSIONS: These data indicate that a two-color T cell flow cytometric crossmatch predicts subsequent pregnancy outcome in patients undergoing immunotherapy for recurrent spontaneous abortion.

Abortion, Habitual↗
PubMed2005

Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4+CD25+ T regulatory cells prevents fetal rejection in a murine abortion model.

Mammalian pregnancy is thought to be a state of immunological tolerance. The mechanisms underlying this phenomenon are still poorly understood. Here, we determined whether an inappropriate function of T regulatory (Treg) cells is involved in the pathogenesis of spontaneous abortion. We evaluated spleen and decidual lymphocytes from CBA/J mice undergoing immunological abortion (DBA/2J-mated) or having normal pregnancy (BALB/c-mated) on day 14 of gestation for ex vivo cytokine production after PMA or paternal antigen (alloantigen) stimulation. Treg activity was characterized by quantifying CD4(+)CD25(+) cells, foxp3 expression, and interleukin-10 secretion. Decidual lymphocytes from abortion CBA/J mice contained a significantly higher frequency of interferon-gamma-producing T cells specific for paternal antigens compared to those from normal pregnancy (7.8% versus 2.7%, P < 0.05). Compared to virgin CBA/J females, normal pregnant mice showed strongly elevated numbers of CD4(+)CD25(+) and interleukin-10(+) Treg cells in the thymus whereas significantly lower frequencies of Treg cells were observed in abortion mice. Very interestingly, CD4(+)CD25(+) Treg cells from normal pregnant and nonpregnant CBA/J mice could inhibit both proliferation and interferon-gamma secretion of lymphocytes from abortion mice in vitro whereas in vivo prevention of fetal rejection could only be achieved after adoptive transfer of Treg cells from normal pregnant mice. Our data suggest that pregnancy-induced Treg cells play a vital role in maternal tolerance to the allogeneic fetus.

Abortion, Spontaneous↗
PubMed2002

Paternal imprinting of Galpha(s) in the human thyroid as the basis of TSH resistance in pseudohypoparathyroidism type 1a.

Albright hereditary osteodystrophy (AHO) is characterized by multiple somatic defects secondary to mutations in the GNAS1 gene. AHO patients with mutations on maternally inherited alleles are resistant to multiple hormones (e.g., PTH, TSH), a variant termed pseudohypoparathyroidism (PHP) type 1a, due to presumed tissue-specific paternal imprinting of the alpha chain of G(s) as demonstrated in murine renal proximal tubule and fat cells. Studies in human tissues thus far revealed imprinting only in pituitary. Because mild hypothyroidism due to TSH resistance occurs in most PHP type 1a patients, we investigated whether Galpha(s) is imprinted in thyroid. Examination of eight normal thyroids demonstrated significantly greater expression from the maternal GNAS1 allele, with paternal Galpha(s) transcripts accounting for only 25.9-40.4%. Expression of NESP55, XLalpha(s), and 1A was uniallelic. We conclude that Galpha(s) is incompletely imprinted in the thyroid, which provides an explanation for mild TSH resistance in PHP type 1a.

Base Sequence↗
PubMed1992

Cutaneous graft-versus-host-like reaction after paternal lymphocyte immunization for prevention of recurrent abortion.

We have presented an immunocompetent patient who, after paternal lymphocyte immunization, developed a GVH-like skin reaction; she recovered spontaneously. This complication is rarely seen. This was the only case observed in our series of over 70 patients immunized. A similar phenomenon was not reported in a larger series by Carp and colleagues (1). However, the case deserves special attention because this reaction can be life-threatening. Therefore, we suggest that paternal lymphocyte immunization should be recommended only for those patients who have undergone a thorough work-up and in whom all causes, other than immunological, for recurrent abortion have been excluded. Even then, this treatment should be given with utmost caution. In view of the above described complication, we believe that more data are still required to justify offering such a treatment modality on a routine basis.

Abortion, Habitual↗
PubMed1997

Failed fertilization after intracytoplasmic sperm injection: the extent of paternal and maternal chromatin decondensation.

OBJECTIVE: To determine the extent of paternal and maternal chromatin decondensation in unfertilized eggs after intracytoplasmic sperm injection (ICSI). DESIGN: Eggs that failed to show two pronuclei (2-PN) 48 hours after ICSI were studied at two different time intervals: at ICSI program inception (group A) and after 8 months (group B). PATIENT(S): Forty-nine patients undergoing IVF cycles. MAIN OUTCOME MEASURE(S): The unfertilized eggs were studied by chromatin staining. RESULT(S): The average fertilization rate from all ICSI cycles in these two groups was 45%. The fertilization rates in groups A and B were 35% and 59%, respectively. In group A, 65% of the unfertilized eggs were characterized by condensed sperm chromatin with 11% showing partial decondensation. In group B, only 28% of the unfertilized eggs demonstrated condensed sperm chromatin, whereas 45% were partially decondensed. In these two groups, no sperm chromatin was detected in 24% of the unfertilized eggs. The maternal chromatin remained at metaphase II in 84% of all unfertilized eggs analyzed. CONCLUSION(S): These observations suggest that the technical problem of deposition of the sperm inside the egg is not the major cause of failure of fertilization rates in ICSI cycles. Rather, it is likely to be the failure to complete both the maternal and paternal chromatin transitions that occur with normal fertilization.

Chromatin↗