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PubMed2006

Reproductive performance in grey seals: age-related improvement and senescence in a capital breeder.

1. Three hypotheses have been advanced to account for age-related improvement in performance: the selection hypothesis predicts improved due to the loss of lower quality phenotypes, the constraint hypothesis predicts individuals improve function, and the restraint hypothesis predicts younger individuals forego or reduce effort because of mortality risks. A decline in age-related performance (i.e. senescence) is predicted by mutation accumulation, antagonistic pleiotropy and disposable soma (wear and tear) hypotheses. 2. Using five measures of performance - birth rate, maternal and pup birth mass, pup weaning mass, weaning success and lactation length - we tested these hypotheses concerning age-related change in reproduction in 279 female grey seals (Halichoerus grypus), ages 4-42 years, over a 23-year period between 1983 and 2005 on Sable Island, Nova Scotia. These females produced 2071 pups. 3. Although body mass of primiparous females increased with age (4-7 years) birth mass of their pups did not, but pup weaning mass did. Second- and third-parity females of the same age as primiparous females gave birth to and weaned heavier pups. However, parity and age were dropped from models when maternal body mass was included. 4. The proportion of females giving birth varied significantly with maternal age, increasing in young females and then declining late in life. Weaning success rate also increased rapidly to about 8 years and subsequently declined in females > 32 years. 5. Generalized additive models indicated nonlinear changes in 3 day body mass (i.e. approximately birth mass) and weaning mass of pups as a function of maternal age, after accounting statistically for the effects of maternal body mass. Mixed-effects, repeated-measures models fitted to longitudinal data further supported the conclusion that pup birth mass and weaning mass vary nonlinearly with maternal age and indicated nonlinear changes in lactation duration. 6. We found some support for the constraint hypothesis, but our findings were not consistent with the selection hypothesis or the restraint hypothesis as the basis for improvement in reproductive performance. 7. Senescence was evident in multiple female and offspring traits, indicating the degeneration in function of several physiological systems as predicted by the disposable soma hypothesis.

Aging↗

PubMed1981

The Seattle longitudinal prospective study on alcohol and pregnancy.

An unselected sample of 1529 women (predominantly white, married, and middle-class) were interviewed during pregnancy regarding their use of alcohol, nicotine, caffeine, drugs, and other variables. Subsets of offspring were examined to assess the relationship of self-reported maternal alcohol use to infant health and development. Multiple regression statistical tests were utilized to permit adjustment for other possibly confounding factors. The following are among those outcomes significantly related to increase maternal alcohol use after adjusting for smoking and other variables: smaller infant size (birth weight, length and head circumference); lower Apgar scores; poorer neonatal habituation; decreased sucking pressure; increased tremulousness and head-turns-to-left; decreased vigorous activity; and a higher frequency of minor dysmorphic characteristics combined with low birth weight and microcephaly. A drinking by smoking interaction was related to poorer newborn conditioning in two separate studies. Significantly lower mental and motor development and lower length and weight were found on follow-up of 468 infants at age 8 months. Follow-up studies continue.

Alcohol Drinking↗

PubMed1978

Psychopathology in adopted-away offspring of biologic parents with antisocial behavior.

A study of 246 adoptees aged 10 to 37 years separated at birth from biologic parents is used to study genetic heritability of antisocial behavior and to delineate the extent and quality of "antisocial spectrum" conditions. Evidence is presented for a genetic factor in adoptee antisocial behavior and for the following as "spectrum" conditions: (1) hysteria in adult females (Briquet's syndrome) or multiple somatic complaints without medical explanation in younger female subjects and (2) mood swings possibly associated with the symptom of audible thoughts.

Adolescent↗

PubMed2003

Effect of GH and IGF-I treatment on reproduction, growth, and plasma hormone concentrations in domestic nutria (Myocastor coypus).

The role of GH and IGF-I in the control of reproduction, growth, and hormone secretion in domestic nutria was examined. In the first series of experiments, we studied the effects of single and multiple (daily for 20 days) injections of recombinant hGH (15 microg/animal) on plasma triiodothyronine (T3), thyroxine (T4), and progesterone (P) concentrations, as well as on the duration of pregnancy (time between start of mating and birth of pups), number of pups born, and body weight of adult females and their newborn pups. In the second series of experiments, the effects of single and multiple (daily for 28 days) injections of recombinant hIGF-I (1 microg/animal) on plasma IGF-I, IGFBP-3, T3, T4 concentrations, the duration of pregnancy, and number of offspring delivered were assessed. It was found that either single or multiple GH treatment resulted in significant increase in plasma T3, T4, but not P concentration. Furthermore, it significantly increased the body weight of adults and newborn pups. No influence of GH on the duration of pregnancy and the number of offspring was observed. IGF-I treatment caused an increase in plasma IGF-I concentration, a reduction in plasma IGFBP-3, T3, and T4 concentrations, and a shorter duration of pregnancy but did not alter the number of pups delivered. Our observations suggest that GH and IGF-I may be involved in the control of hormone secretion, growth, and reproduction in domestic nutria. Reproductive processes are controlled by IGF-I rather than by GH, whilst GH may be involved in the stimulation of prenatal and postnatal growth. The differential effects of these substances on thyroid hormones and reproductive parameters suggest that the actions of GH on these processes are probably not mediated by IGF-I.

Animals↗

PubMed1982

The ring chromosome 13 syndrome.

A study of the ring chromosome 13 syndrome is presented with detailed clinical and cytogenetic features of three new unrelated cases. The clinical limits of this syndrome can now be defined. An analysis of these cases together with those in the literature indicates that the syndrome forms a continuous spectrum, and no further taxonomic subdivision is possible at this stage of knowledge. The chromosome breakpoints in the first two cases are 13p11 and 13q32 and in the third case 13p11 and 13q33 or 13q34. All described cases of the ring 13 syndrome have breakpoints within the region bounded by bands 13q21 to 13q34. All rings are negative for silver banding. Peripheral blood cultures showed an average of 88% of metaphases to be 46,XX,r(13), with the remaining 12% manifesting either random loss or ring duplication. The rings vary in size and show a variable number of centromeres. An estimate of the birth incidence of this condition in the Anglo-Saxon population is 1 in 58,000. Parents of affected children are clinically and cytogenetically normal, the rings in affected offspring being meiotic in origin.

Abnormalities, Multiple↗

PubMed2000

Obstetric outcome and follow-up of children born after in vitro fertilization (IVF).

In vitro fertilization (IVF) is a well established and effective method for the treatment of infertility, but there is concern about the health of children born as a result of this procedure. The introduction of new technologies, such as intracytoplasmic sperm injection (ICSI), has increased concern that the offspring from such techniques may be at increased risk, particularly of malformations. Studies on obstetric and neonatal outcome and early infant development after IVF obtained from a Medline search were reviewed. Children born after IVF had a considerably higher risk of being born pre-term and with a lower birth weight than children conceived naturally. A high incidence of multiple births and maternal characteristics were the main factors responsible for the increase in adverse outcome. Novel strategies in assisted reproduction, including the development of single embryo transfer regimens and avoidance of multiple births, are required. There is also a need for further developmental follow-up of children born after assisted conception, especially those born after ICSI.

Journal Article↗

PubMed1975

Congenital malformations due to anticonvulsive drugs.

A retrospective study of congenital malformations in the offspring of 20 women who received antiepileptic drugs during pregnancy is presented. Of 56 births, 9 children (16%) were born with malformations. Four children were born dead or died shortly after delivery. Congenital heart disease, cleft lip with or without cleft palate, neural tube defects, and skeletal abnormalities were the commonest anomalies found. One child had a recognizable pattern of multiple malformations. The increased perinatal mortality was mainly due to congenital malformations and spontaneous hemorrhage. The teratogenic activity of anticonvulsant drugs is mediated by interference with folic acid metabolism, and such activity might be influenced by hereditary and environmental factors. Bearing in mind the importance of anticonvulsant therapy in epilepsy, there is certainly need for an investigation of the problem in a larger and more representative birth population than that described.

Abnormalities, Drug-Induced↗

PubMed1989

Computerised tomography in schizophrenia. Familial versus non-familial forms of illness.

Findings on CT and demographical or clinical data in 80 patients with DSM-III schizophrenia and 45 medical controls were evaluated. Multiple-discriminant analysis showed that the enlargement of the third ventricle and frontal and parietal atrophy could significantly predict the diagnosis of schizophrenia. Widening of Sylvian fissures and parietal atrophy differentiated familial schizophrenics of both horizontal transmission (who had affected siblings) and vertical transmission (who had affected parents or/and offspring) from non-familial patients. Parietal atrophy and a history of birth complications differentiated horizontal from vertical transmission. The CT findings together with some clinical characteristics could differentiate the three subgroups classified by the hereditary form; thus each of these subgroup may belong to a different disease entity, of a different pathophysiology.

Adult↗

PubMed2002

Mother's age and daughter's fecundity. An epidemiological analysis of late 19th to early 20th century family reconstitutions.

BACKGROUND: At both ends of the female reproductive span, the risk of reproductive problems is increased. We hypothesize that this is partly explained by inadequate maturation of oocytes ('pre-ovulatory overripeness'). As this phenomenon has been shown to lead to gonadal anomalies in the offspring of animals, we tested the prediction that daughters of older and very young mothers more often suffer reproductive problems due to ovarian maldevelopment. METHODS: We analysed family reconstitutions of 1907 women born in Rotterdam, the Netherlands, between 1873 and 1902. We defined several measures of fecundity based on numbers, birth rates and fates of offspring. We made use of general estimating equations (GEE), a statistical technique that allowed simultaneous analysis of different births per woman while controlling for various time-dependent or time-independent co-variables. RESULTS: The results indicated an increased risk of childlessness (adjusted odds ratio (aOR = 2.6, 95% CI : 1.1-7.4), stillbirth (aOR = 2.5, 95% CI : 1.1-5.6) and multiple birth (aOR = 2.1, 95% CI : 0.8-5.4) for daughters of mothers of >or=40 years as compared to daughters born to mothers of intermediate age (24-30 years). Daughters of mothers of <or=20 years, on the other hand, did not appear to have reduced fecundity. CONCLUSION: The results point to a decreased fecundity of daughters of older mothers, but not of daughters of younger mothers. The inconsistency of the results with respect to the oocytal-maturation hypothesis points to the action of other causal or non-causal mechanisms.

Adolescent↗

PubMed1989

[Abnormalities among newborn children born to immigrants in Denmark in the period 1983-1987].

It has recently been discussed whether there was a higher incidence of congenital malformations among newborns of immigrant mothers than among Danish infants. The study is based on information retrieved from two registries in the Danish National Board of Health, both with national coverage: The Medical Birth Register and the Register of Congenital Malformations. All livebirths in Denmark, born to women from Denmark, Scandinavia, Yugoslavia, Turkey, Pakistan, Morocco, Iran and Vietnam in the years 1983-1987, more than 240,000 infants, were included. When comparing the birth prevalence of congenital malformations in the various groups, the observed rate is corrected for maternal age and parity distribution, fathers' occupation (indicating the social position) and county of delivery, as ascertainment varies between hospitals. This part of the analysis did not support the observation of an increased incidence among offspring of immigrant women. A more detailed analysis, based on a multiplicative Poisson-model, compares the three largest groups: Danish, Turkish and Pakistani mothers. Evaluating the influence of maternal age, father's occupation and county of delivery, the result is that the differences observed can, to a large degree, be explained by these three factors, especially the county of delivery. The remaining differences are no larger than can be explained as random. We were thus unable to support the debated observation on a higher incidence of congenital malformations among infants born to immigrant mothers.

Congenital Abnormalities↗

PubMed2004

Maternal basking behaviour determines offspring sex in a viviparous reptile.

Two primary dichotomies within vertebrate life histories involve reproductive mode (oviparity versus viviparity) and sex determination (genotypic sex determination versus environmental sex determination). Although reptiles show multiple evolutionary transitions in both parameters, the co-occurrence of viviparity and environmental-dependent sex determination have heretofore been regarded as incompatible. Our studies on the viviparous lizard Niveoscincus ocellatus show that the extent of basking by a female influences the sex of her offspring. Critically, our data reveal this effect both in the field (via correlations between date of birth and litter sex ratio) and in a laboratory experiment (females with reduced basking opportunities produced more male offspring). Changes in thermoregulatory behaviour thus allow pregnant female lizards to modify the sex of their offspring.

Animals↗

PubMed2001

The position of t(11;22)(q23;q11) constitutional translocation breakpoint is conserved among its carriers.

The t(11;22)(q23;q11) translocation is the most common recurrent balanced translocation described in humans. Carriers are phenotypically normal and often go undetected until diagnosis as a result of infertility investigations or following the birth of chromosomally unbalanced offspring. Efficient diagnostics of t(11;22) is important for children born to carriers of the translocation and for prenatal and pre-implantation diagnosis. The translocation breakpoint on chromosome 22 is located within a region containing low copy repeats, and this site is one of the last unfilled gaps in the sequence of this chromosome. This autosome harbors multiple other low copy repeats, which have been entirely sequenced. We report a combined sequencing and fiber FISH breakpoint characterization in five translocation carriers. From one carrier a cosmid library was constructed, and two chimeric cosmids (cos4_der11 and cos6_der22) were sequenced, which showed that strong palindromes (or inverted repeats) occur on both chromosomes. The translocation breakpoints occur at the tip of both inverted repeats. The palindrome on chromosomes 22 and 11 is composed of 852 and 166 bases, respectively. Four additional carriers were studied using fiber FISH with a resolution limit of 2 kb. Analysis of breakpoints on the DNA sequence level, or at the level of fiber FISH, indicate that they occur at the same position on both chromosomes in all five carriers. Using cos6_der22, PAC 158L19 and BAC 3009A19, we demonstrate that FISH is an attractive alternative in molecular diagnostics of t(11;22), as PCR assays are not reliable, due to the presence of numerous copies of low copy repeats.

Adult↗

PubMed2002

Autoimmune and pregnancy complications in the daughter of a kidney transplant patient.

BACKGROUND: Immunosuppressive agents taken by pregnant organ transplant recipients readily cross the placenta during development of the fetal immune system. There are few data on the long-term implications for the progeny, but evidence from animal studies suggest that second and third generations of organ transplant patients may be at risk for autoimmune disorders and reproductive problems. METHODS: We present the 23-year-old daughter of a renal allograft recipient exposed to azathioprine 75 mg/day and prednisone 5 mg/day throughout her mother's pregnancy. RESULTS: During the daughter's first pregnancy, she developed multiple autoantibodies, Raynaud's phenomenon, and fetal death occurred at 20 weeks gestation. The second pregnancy was complicated by systemic lupus erythematosus, preeclampsia, and the birth of a preterm male infant. CONCLUSIONS: It is uncertain whether the autoimmune manifestations and obstetric complications in this patient were related to fetal exposure to immunosuppressive drugs. Nevertheless, further studies on the health and pregnancies of adult offspring of transplant patients are warranted.

Adolescent↗

PubMed1998

Paternal work in the power industry: effects on children at delivery.

Although reports on reproductive disturbances among occupational groups of electrical workers have been discussed, few studies have focused explicitly on the children of workers employed in the power industry. Birth outcome and cancer in the offspring of fathers who were exposed to electric and magnetic fields at time of sperm production were studied in two cohorts. In Study 1, male occupation in the power industry was identified in censuses. Study 2 is a prospective cohort study of newly employed power industry workers. Birth data were obtained by record linkage between censuses and several available health registers in Sweden. Multiple births, birth weight, sex, survival, congenital malformations, and cancer have been analyzed with relation to the father's exposure to electric and magnetic fields one year before the child was born. There were six cancer cases among infants in the exposed group (2.4 expected) and six in the unexposed group (3.2 expected) in Study 1. Jointly, the 12 cancer cases found among the infants were more than expected (P = 0.02). However, this total excess may be random. No cancer cases were observed in the prospective study. For chromosomal abnormalities, such as Down's syndrome, one case was observed among infants of exposed fathers and three cases among unexposed fathers in Study 1. In Study 2, no cases were observed. There was a slightly higher proportion of malformation diagnoses among infants of exposed fathers than among infants of unexposed fathers in Study 2, but this could be random (odds ratio = 1.59; 95% Confidence interval 0.43-1.48). No clear-cut effects on infants fathered by men who were exposed to electric and magnetic fields around the time of sperm production could be seen in these two studies.

Adult↗

PubMed2006

Reproductive and neurobehavioural toxicity study of Ponceau 4R administered to mice in the diet.

Ponceau 4R was given to mice in the diet at levels of 0 (control), 0.12%, 0.24%, and 0.48% from 5 weeks of age of the F(0) generation to 9 weeks of age of the F(1) generation, and selected reproductive and neurobehavioural parameters were measured. There was no adverse effect of Ponceau 4R on litter size, litter weight or sex ratio at birth. The average body weight of male and female offspring was increased significantly in the high-dose group at postnatal days (PNDs) 0, 4 and 21. In behavioural developmental parameters, surface righting at PND 4 was affected significantly in the high-dose group in male offspring. Other variables measured showed no consistently significant adverse effect on either sex in the lactation period. In multiple water T-maze performance in the F(1) generation, the time taken was significantly longer than the control in the middle-dose and high-dose groups in males, and those effects were significantly dose-related (P<0.01). The dose level of Ponceau 4R in the present study produced no adverse effect on reproduction, and a few adverse effects on neurobehavioural parameters in mice. The non-observed adverse effect level (NOAEL) was presumed to be 0.12% in the diet (approximately 205mg/kg per day) for maze learning by males in the F(1) generation. Nevertheless, the middle-dose and high-dose levels were in excess of the acceptable daily intake (ADI) of Ponceau 4R (0-4.0mg/kg body weight), and the actual dietary intake of Ponceau 4R in humans is presumed to be much lower. It would appear, therefore, that the level of dietary intake of Ponceau 4R is unlikely to produce any adverse reproductive or neurobehavioural effect in humans.

Animals↗

PubMed1999

Pregnancy and child outcome after assisted reproduction techniques.

The introduction and widespread application of assisted reproduction techniques have raised major concern about the outcome of resulting pregnancies, as well as about the offspring's health. It seems that pregnancies achieved after standard in-vitro fertilization (IVF) bear an increased risk for prematurity and low birth weight. On the other hand, pregnancy outcome of singletons achieved after intracytoplasmic sperm injection (ICSI) and after the transfer of frozen-thawed embryos is similar to that of spontaneously conceived singletons, and pregnancy complications are related only to gestation multiplicity. The incidence of congenital and chromosomal anomalies after standard IVF seems to be similar to that expected in the general population. The prevalence of congenital malformations does not seem to be higher after ICSI. On the other hand, there is a slightly increased risk for transmission of chromosomal aberrations of paternal origin and a higher risk of de novo, mainly sex-chromosomal aberrations. Postnatal growth and development of children born after standard IVF and cryopreservation seem to be within the normal ranges. Growth of ICSI children is also normal while their mental development needs further investigation. Family functioning in assisted reproduction families is better.

Child Development↗

PubMed1984

Congenital malformations and maternal drinking water supply in rural South Australia: a case-control study.

A case-control study, carried out in the Mount Gambier region of South Australia, investigated the relationship between mothers' antenatal drinking water source and malformations in offspring. It was prompted by earlier descriptive findings of a statistically significant, and localized, increase in the perinatal mortality rate in Mount Gambier, due principally to congenital malformations affecting the central nervous system and multiple organ systems. Available for statistical analysis were 218 case-control pairs, from the period 1951-1979, individually matched by hospital, maternal age (+/- 2 years), parity and date of birth (+/- 1 month). Compared with women who drank only rainwater during their pregnancy (relative risk (RR) = 1.0), women who consumed principally groundwater had a statistically significant increase in risk of bearing a malformed child (RR = 2.8). Statistically significant risk increases occurred specifically for malformations of the central nervous system and musculoskeletal system. Reanalysis of the data by estimated water nitrate concentration demonstrated a nearly threefold increase in risk for women who drank water containing 5-15 ppm of nitrate, and a fourfold increase in risk for those consuming greater than 15 ppm of nitrate. A seasonal gradient in risk was evident among groundwater consumers, ranging from 0.9 for babies conceived in winter, 3.0 in autumn, to 7.0 and 6.3 for spring and summer conceptions, respectively. Linear logistic regression analysis, controlling for risk factors not accounted for in the study design, showed that maternal water supply, infant's sex, and mother's area of residence all contributed significantly to the risk of malformation. These results are discussed in relation to previous experimental and human descriptive studies, suggesting a plausible mechanism for nitrate-induced teratogenesis.

Abnormalities, Drug-Induced↗

PubMed1995

Genetic-environmental interaction in the genesis of aggressivity and conduct disorders.

BACKGROUND: The purpose of this study was to determine the effect of an adverse adoptive home environment on adoptee conduct disorder, adult antisocial behavior, and two measures of aggressivity, all of which are behaviors that contribute to adult antisocial personality disorder and that also are associated with increased vulnerability to drug abuse and/or dependence. METHODS: The study used an adoption paradigm in which adopted offspring who were separated at birth from biologic parents with documented (by prison and hospital records) antisocial personality disorder and/or alcohol abuse or dependence were followed up as adults. They and their adoptive parents were interviewed in person. These adoptees were compared with controls whose biologic background was negative for documented psychopathologic behavior. Subjects were 95 male and 102 female adoptees and their adoptive parents. RESULTS: Multiple regression analysis was used to measure separately genetic and environmental effects. It showed that (1) a biologic background of antisocial personality disorder predicted increased adolescent aggressivity, conduct disorder, and adult antisocial behaviors, and (2) adverse adoptive home environment (defined as adoptive parents who had marital problems, were divorced, were separated, or had anxiety conditions, depression, substance abuse and/or dependence, or legal problems) independently predicted increased adult antisocial behaviors. Adverse adoptive home environment interacted with biologic background of antisocial personality disorder to result in significantly increased aggressivity and conduct disorder in adoptees in the presence of but not in the absence of a biologic background of antisocial personality disorder. CONCLUSIONS: Environmental effects and genetic-environmental interaction account for significant variability in adoptee aggressivity, conduct disorder, and adult antisocial behavior and have important implications for the prevention and intervention of conduct disorder and associated conditions such as substance abuse and aggressivity.

Adoption↗