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PubMed1982

Reproductive behavior in Varecia variegata.

Testicle size during the breeding season is related to age and previous social environment of the male. The size of testicles in adult males exceeds that of young males. Adult males' testicles are much larger than the testicles of young males; enlargement starts 2-3 months prior to the breeding season, peaking around copulation day. Subadult males (3-year-olds) are able to develop full-sized testicles and sire offspring, but did so only when housed with adult females and not with their family group. Although females may reach sexual maturity in their second breeding season after birth, they do not necessarily breed successfully. Vaginal estrus lasts considerably longer (2-3 days) than behavioral estrus (6-12 h). Different stages of vaginal estrus can visually be determined by the development of the vaginal region (swelling; appearance of pink point; long, pink slash; opening to round pink circle, and in the latter stage, by smears, confirming the different physiological stages, proestrus, estrus, metestrus). Behavioral estrus appears in the last hours of vaginal estrus. Captive adult females show increasingly hostile behavior to their maturing daughters. These have to be removed from the group when they are sexually mature. The same degree of hostility can be found between fathers and subadult sons during the breeding season. Dominant males show a typical 'guarding behavior' over the entire period of behavioral estrus of the female. They remain close to the female, vigorously preventing other males from approaching or mating with the female. At the beginning and the end of copulations, the female shows a sequence of aggressive behaviors towards the dominant male. Successful copulations can be determined by their duration (1-2 min), and a head-twisting movement of the male during ejaculation. Normally 16-25 copulations occur on copulation day, usually all with the same partners. The average gestation length is 102.5 days. Adult females normally give multiple births, whereas primiparous females tend to have single infants.

Age Factors↗

PubMed2004

[Study on the association between reduced folate carrier gene polymorphism and congenital heart defects and cleft lip with or without cleft palate].

OBJECTIVE: To study the association between reduced folate carrier gene (RFC1) polymorphism and congenital heart defects (CHD) as well as cleft lip with or without cleft palate (CLP) and to provide epidemiological evidence on genetic markers of CHD and CLP. METHODS: RFC1 (A80G) genotype was detected using RFLP-PCR for blood DNA of the 67 triads with nonsyndromic CHD-affected child, the 82 triads with child-affected cleft lip with or without CLP and the 100 control families without child-affected birth defects. We performed a family-based association test and analyzed the interaction between RFC1 A80G genotype and maternal periconceptional supplementation of folic acid. RESULTS: Offspring of mothers who did not take folic acid had an elevated risk for CHD when comparing with offspring of mothers who did (OR = 2.68, 95% CI: 1.14 - 6.41). There was a statistical association between the risk of CHD and maternal periconceptional folic acid supplementation (chi(2) = 6.213, P < 0.05). In the family-based association test, G allele was positively associated with an increased risk for children CHD (Z = 2.140, P < 0.05) while G allele of RFC1 (A80G) polymorphism might increase the risk for CHD. Elevated risks for either CLP group were not observed between RFC1 genotype using or not using folic acid. CONCLUSION: Our findings suggested that the G allele was likely to be a genetically susceptible allele for CHD. There was possible association between offspring with GG, GA genotype and maternal periconceptional folicacid deficiency.

Abnormalities, Multiple↗

PubMed1991

Prenatal lead exposure in the rat during the third week of gestation: long-term behavioral, physiological, and anatomical effects associated with reproduction.

Sprague-Dawley dams were administered lead acetate (0.1%) in their drinking water from Day 14 of gestation to parturition to determine whether exposure of the fetus to elevated lead (Pb) levels during a period of rapid differentiation of the hypothalamic-pituitary-gonadal (HPG) axis would disrupt HPG function in adulthood. At birth, offspring from 20 Pb-treated and 10 control dams were weighed and 2 litter representatives from each sex were fostered to untreated dams. Animals were weaned at 26 days of age and subsequently group housed by sex and treatment. Blood Pb levels in prenatally exposed pups were below the limits of detectability at weaning. Female offspring from Pb-treated dams were found to have a significant delay in the day of vaginal opening. In a sample of lead exposed females, 50% were found to exhibit prolonged and irregular periods of diestrous which was accompanied by an absence of observable corpora lutea when they were euthanized at 83 days of age. Male offspring from these dams were found to have decreased sperm counts at 70 and 160 days of age and to exhibit significantly less territorial scent marking and masculine sex behavior in adulthood compared to controls. Azoospermia was observed in 1 lead exposed animal at 70 days of age and 2 animals at 160 days. Enlarged prostates were observed in Pb-exposed males measured at 160 days, but other sex organ weights were normal. Volume of the sexually dimorphic nucleus of the preoptic area of the hypothalamus in adulthood was significantly reduced by approximately 35% in Pb-exposed males. Pulsatile release of gonadotropins, measured in castrated adult animals of both sexes, revealed irregular release patterns of both FSH and LH in some Pb animals which were not observed in controls. The overall pattern of results suggests that multiple levels of the HPG axis can be affected by exposure to Pb during a period of gestation when structures related to the HPG axis are undergoing rapid proliferation. These data indicate that lead exposure during this period places the exposed animal at significant risk for reduced reproductive capacity in adulthood.

Animals↗

PubMed1998

Fetotoxicity and teratogenesis of SWL treatment in the rabbit.

The potential effects of extracorporeal application of shockwaves on an embryo or fetus were explored in an animal model. In experimental Series A, the fetuses of 30 gravid rabbits were exposed to piezoelectrically induced and sonographically guided shockwaves on Day 25 or 20 of gestation under technical conditions corresponding to extracorporeal lithotripsy in humans. Fetotoxicity was examined by abdominal section 24 hours or 9 days later, and immediate/intermediate damage was assessed (resorptions, viability, gross injuries, and microscopic lesions of the target and neighboring fetuses). In series B, the kidneys of an additional 28 gravid rabbits (including a control group) were exposed to the same shockwave treatment on Day 11 of gestation in order to investigate indirect embryotoxic effects, including teratogenic potency. One day before the expected birth, the maternal kidneys, uteri, and adjacent organs were examined for lesions, and the 156 offspring were assessed for embryolethal, embryonoxious, or teratogenic sequelae. Shockwave targeting of the cranium, thorax, abdomen, or placenta was usually lethal to the fetuses. When the uterine wall or the space between two fetuses was targeted, the fetuses suffered from superficial hematoma, as was found in the surrounding soft tissues within a radius of 1.5 cm. Fetuses outside this region were vital and free of lesions. Shockwave treatment of the maternal kidney resulted in renal petechial hemorrhage or subcapsular hematoma. However, statistically significant embryotoxic or teratogenetic effects could be demonstrated neither from maternal data (resorptions) nor from fetal findings (body measurements, vitality test, inner organs, skeletal deformities). When using a piezoelectric lithotripter with a small focus of high energy, lesions of a fetus are to be expected only when it is located in or close to the focus. It seems that embryotoxic or teratogenic sequelae do not occur when shockwaves are focused outside the uterus. Nonetheless, this preliminary research does not justify clinical use of extracorporeal shockwave lithotripsy in pregnant humans.

Abnormalities, Multiple↗

PubMed1999

Preeclampsia in twin pregnancies: incidence and outcome.

OBJECTIVES: To confirm the increased incidence of preeclampsia in twin pregnancy and to determine the relationship to zygosity and placentation; to consider the perinatal outcome of twin pregnancies in this condition. METHODS: Retrospective study of all twin pregnancies (n = 2473) identified from the Aberdeen Maternity and Neonatal Databank to women resident in the Grampian Region of Scotland for the period 1950-1995. RESULTS: The increased relative risk for gestational hypertension, preeclampsia, and eclampsia in twin pregnancies compared to singleton pregnancies has been confirmed as significant both in primiparas and multiparas with little variation in rates over the time period under review. Neither the sex of the offspring nor zygosity influences the incidence of hypertensive disease, whereas preeclampsia is more common in association with monochorionic placentation. As the birth weight was lower and placental weight greater in MzMc twins compared to either MzDc or DzDc, there was a higher placental index in such cases. No difference in the birth weights of individual twins, the difference in birth weights between the twins, placental weight, or placental index were found in relation to hypertensive disease. Gestation at delivery was earlier in normotensive twin pregnancies than in those women who developed a hypertensive problem. This leads to a higher perinatal death rate and lower survival rate for the babies in normotensive women with a twin pregnancy. CONCLUSION: Although gestational hypertension, preeclampsia, and eclampsia all occur more commonly in twin pregnancy, this does not lead to significant growth retardation nor discordant fetal growth and a poor outcome for the twins. Although the incidence of preeclampsia is higher in twin pregnancies with monochorionic placentation, this does not seem to be mediated by deficiencies in placental development as assessed in this study.

Birth Weight↗

PubMed1995

Differential fertility of mothers of twins and mothers of singletons: study in Limon, Costa Rica.

The reproductive performance of mothers of twins is of interest from an evolutionary perspective. Because mothers of twins have the potential of leaving a greater number of offspring, they could be favored by natural selection. At the same time, twin pregnancies are known to be associated with higher pre- and postnatal mortality. Thus mothers of twins at least have potentially higher fertility, a potential that may be hampered by greater mortality of twins. Here, I examine the completed fertility of 149 females, 50 years of age and older, from Limon, Costa Rica. In particular, the number of surviving children of mothers of twins and mothers of singletons at the time of the interview is compared. In this sample mothers of twins have a higher fertility at the end of their reproductive career. Their selection coefficient indicates that natural selection favors them through differential fertility.

Costa Rica↗

PubMed1997

Reproductive pattern, perinatal mortality, and sex preference in rural Tamil Nadu, south India: community based, cross sectional study.

OBJECTIVES: To study reproductive pattern and perinatal mortality in rural Tamil Nadu, South India. DESIGN: Community based, cross sectional questionnaire study of 30 randomly selected areas served by health subcentres. SETTING: Rural parts of Salem District, Tamil Nadu, South India. SUBJECTS: 1321 women and their offspring delivered in the 6 months before the interview. MAIN OUTCOME MEASURES: Number of pregnancies, pregnancy outcome, spacing of pregnancies, sex of offspring, perinatal and neonatal mortality rates. RESULTS: 41% of the women (535) were primiparous; 7 women (0.5%) were grand multiparous (> 6 births). The women had a mean age of 22 years and a mean of 2.3 pregnancies and 1.8 live children. The sex ratio at birth of the index children was 107 boys per 100 girls. The stillbirth rate was 13.5/1000 births, the neonatal mortality rate was 35.3/1000, and the perinatal mortality rate was 42.0/1000. Girls had an excess neonatal mortality (rate ratio 3.42%; 95% confidence interval 1.68 to 6.98; this was most pronounced among girls born to multiparous women with no living sons (rate ratio 15.48 (2.04 to 177.73) v 1.87 (0.63 to 5.58) in multiparous women with at least one son alive). CONCLUSIONS: In this rural part of Tamil Nadu, women had a controlled reproductive pattern. The excess neonatal mortality among girls constitutes about one third of the perinatal mortality rate. It seems to be linked to a preference for sons and should therefore be addressed through a holistic societal approach rather than through specific healthcare measures.

Abortion, Spontaneous↗

PubMed2005

The host-parasite relationship in bovine neosporosis.

Infection with the protozoan parasite Neospora caninum is thought to be a major cause of reproductive failure in cattle worldwide. Cattle infected with the parasite are three to seven times more likely to abort compared to uninfected cattle. The parasite may be transmitted to cattle through the ingestion of oocysts that are shed in the faeces of acutely infected dogs (definitive host of N. caninum) or by congenital infection from mother to foetus via the placenta. Interestingly, transplacental transmission can occur over consecutive pregnancies and congenitally infected heifers can transmit the parasite to their own offspring. This repeated vertical transmission observed in naturally infected cattle suggests that cattle do not easily develop effective immunity to the parasite, presenting a significant challenge to the development of a control strategy based on vaccination. Neosporosis is a disease of pregnancy and studying the bovine maternal and foetal immune responses during pregnancy will help us to understand the change in the balance between the parasite and the host that may result in disease of the foetus. Studies in non-pregnant cattle and in murine models of infection have shown the importance of T-helper 1-type immune responses involving pro-inflammatory cytokines, such as IFNgamma and IL-12, in limiting intracellular multiplication of the parasite. During pregnancy, changes occur in the immune system allowing the mother to accept the foetal allograft. Research in other species has stressed the crucial role of T-helper 2-type cytokines at the materno-foetal interface in maintaining the pregnancy and regulating the potentially damaging effect of Th-1 responses. Studies in cattle have shown that cell proliferation and IFNgamma responses may be significantly down-regulated around mid-gestation. This may mean that cattle are less able to cope with N. caninum infection at this time and are more likely to transmit the parasite to the foetus. Another important factor is the gestational age and hence immuno-competence of the foetus at the time of infection. Early in gestation, N. caninum infection of the placenta and subsequently the foetus usually proves fatal, whereas infection occurring in mid to late pregnancy may result in the birth of a congenitally infected but otherwise healthy calf. Studies of foetal immune responses have shown that at 14 weeks of gestation, lymphocytes only respond to mitogen, while by 24 weeks (mid-gestation), they respond to antigen by proliferating and releasing IFNgamma. Clearly, there are several factors influencing the outcome of N. caninum infection in pregnancy: the timing, quantity and duration of parasitaemia, the effectiveness of the maternal immune response and the ability of the foetus to mount an immune response against the parasite. The challenge is to design a vaccine that will prevent foetal infection by N. caninum. This is likely to involve a fine balancing act with the immune system that will allow intervention in a manner that will tip the host-parasite balance in favour of the host without compromising the pregnancy.

Animals↗

PubMed2004

Rotenone potentiates dopamine neuron loss in animals exposed to lipopolysaccharide prenatally.

We previously demonstrated that treating gravid female rats with the bacteriotoxin lipopolysaccharide (LPS) led to the birth of offspring with fewer than normal dopamine (DA) neurons. This DA neuron loss was long-lived and associated with permanent increases in the pro-inflammatory cytokine tumor necrosis factor alpha (TNFalpha). Because of this pro-inflammatory state, we hypothesized that these animals would be more susceptible to subsequent exposure of DA neurotoxins. We tested this hypothesis by treating female Sprague-Dawley rats exposed to LPS or saline prenatally with a subtoxic dose of the DA neurotoxin rotenone (1.25 mg/kg per day) or vehicle for 14 days when they were 16 months old. After another 14 days, the animals were sacrificed. Tyrosine hydroxylase-immunoreactive (THir) cell counts were used as an index of DA neuron survival. Animals exposed to LPS prenatally or rotenone postnatally exhibited a 22% and 3%, respectively, decrease in THir cell counts relative to controls. The combined effects of prenatal LPS and postnatal rotenone exposure produced a synergistic 39% THir cell loss relative to controls. This loss was associated with decreased striatal DA and increased striatal DA activity ([HVA]/[DA]) and TNFalpha. Animals exposed to LPS prenatally exhibited a marked increase in the number of reactive microglia that was further increased by rotenone exposure. Prenatal LPS exposure also led to increased levels of oxidized proteins and the formation of alpha-Synuclein and eosin positive inclusions resembling Lewy bodies. These results suggest that exposure to low doses of an environmental neurotoxin like rotenone can produce synergistic DA neuron losses in animals with a preexisting pro-inflammatory state. This supports the notion that Parkinson's disease (PD) may be caused by multiple factors and the result of "multiple hits" from environmental toxins.

Animals↗

PubMed2003

Sibling effect on atopy in children of patients with asthma.

BACKGROUND: Multiple population studies have shown the presence of a sibling effect on atopic disease. However, it is unclear if the sibling effect is also of importance in subjects who are genetically at high risk for the development of atopy. OBJECTIVE: To study the presence of a sibling effect on markers of atopy (serum total IgE, specific IgE, skin tests) and asthma (bronchial hyper-responsiveness to histamine) in families ascertained through a parent with asthma. METHODS: First-degree offspring in 200 asthma families were studied (n = 541). Mixed effects regression models were used to account for the dependence of the observations within a family, and to adjust for possible confounding variables. RESULTS: Multiple regression analysis showed that having older siblings was inversely related to atopy, defined as >/= 2, >/= 3, >/= 4, or >/= 5 skin tests (P = 0.07-0.009). In addition, family size (number of siblings) had a significant protective effect on the presence of specific IgE to common aeroallergens (P = 0.03). Exposure to cigarette smoke in the first 3 years of life significantly increased the risk of having specific IgE to common aeroallergens (P = 0.04). No sibling effect was detected for serum total IgE or bronchial hyper-responsiveness to histamine. CONCLUSIONS: This study shows a protective sibling effect on the presence and severity of atopy but not on bronchial hyper-responsiveness in children who are genetically at risk. The identification of the sibling effect in high-risk families stresses the need to understand the basis of this effect, in order to design future prevention programmes.

Adolescent↗

PubMed1998

Multiple pregnancies obtained by testicular spermatid injection in combination with intracytoplasmic sperm injection.

Recent studies have shown that the injection of spermatid cells into the human oocyte can result in normal fertilization, embryo development and even delivery of live, healthy offspring. In our study, 23 azoospermic cases with severe spermatogenetic defects in their testicular biopsy are presented. The serum follicle stimulating hormone (FSH) concentrations and histopathological results of these males have been documented and compared in terms of fertilization and embryo development. The mean FSH value of the azoospermic males was 15.8 +/- 2.3 mIU/l, ranging from 1.6 to 39 mIU/l. Elongated spermatids were used in three cases only, as these more mature forms were mostly present in the testicular sample. In the remaining 20 cases, only round spermatids were found for use in intracytoplasmic sperm injection (ICSI). The fertilization rate with two pronuclei was 31.3%. The fertilization rate was found to be as high as 71% in three patients in the elongating and elongated spermatids group and as low as 25.6% in the round spermatid group. A few immature, non-motile spermatozoa were seen in only two cases from the elongated spermatid group. However, in the remaining cases, no spermatozoa were observed. The number of pronuclear (PN) arrest was quite high when only round spermatids were used (36.1%). Total fertilization failure was observed in two cases from the round spermatid group with Sertoli cell only and germ cell aplasia. A total of three pregnancies was achieved in 23 cases (13.0%), two from the elongated spermatid group and one from the round spermatid group. One biochemical pregnancy with a round spermatid resulted in an early spontaneous abortion and surprisingly, the remaining pregnancies were achieved with elongated spermatids resulting in multiple pregnancies. One twin and one triplet pregnancy were established following four embryo transfers in each patient. The twin pregnancy resulted in a live birth with two healthy babies; unfortunately, the triplet pregnancy ended in an abortion at 11 weeks. The use of testicular spermatids in the treatment of non-obstructive azoospermia may give hope by offering a novel treatment model. In cases with very severe spermatogenetic defect, even multiple pregnancies can be achieved with elongated spermatid cells by yielding a high implantation rate. However, the efficiency of round spermatids in achieving fertilization and pregnancy was disappointing.

Adult↗

PubMed1997

Does light-to-moderate alcohol consumption during pregnancy increase the risk for renal anomalies among offspring?

OBJECTIVE: To determine the association between light-to-moderate prenatal alcohol exposure and congenital renal anomalies. METHODS: Data from the population-based Atlanta Birth Defects Case-Control Study were used to examine the association between selected renal anomalies and self-reported maternal alcohol consumption during the period from 1 month before through 3 months after conception. Case infants were ascertained by a population-based birth defects registry with active case ascertainment; the case group consisted of 158 infants, born during 1968 through 1980 to metropolitan Atlanta residents, in whom these renal anomalies had been diagnosed. Two control groups were used. One had 3029 infants without birth defects, and the other had 4633 infants with birth defects exclusive of the urinary tract who were born during the same period. RESULTS: Overall, there was a moderate association between renal anomalies and moderate prenatal alcohol exposure (odds ratio, 1.5; 95% confidence interval, 1.0 to 2.3). When the renal anomalies were subclassified, moderate prenatal alcohol exposure was significantly associated only with renal agenesis or hypoplasia (odds ratio, 2.5; 95% confidence interval, 1.2 to 5.1), and within this group only infants with bilateral defects and other major anomalies in addition to renal agenesis or hypoplasia had significantly elevated risks. There were no significant associations between reported light consumption and any category of the selected renal anomalies. No conclusions could be reached for reported heavy consumption because of sparse data. Adjustments for potential confounding factors did not alter these results. CONCLUSION: This study suggests that moderate alcohol consumption during pregnancy may increase a woman's risk of giving birth to a child with renal agenesis or hypoplasia.

Abnormalities, Multiple↗

PubMed1975

Twinning rates among women at the end of their reproductive span and their relation to age at menopause;.

A review of studies on twinning has shown that dizygotic (DZ) twinning rates among women from general populations characteristically peak at ages 35-39, then decline sharply. Analysis of genealogical data from the Archives of the Mormon Church indicates that women who are dizygous twins themselves or the sibs of dizygous twins have a higher twinning rate among their offspring than do women from the general population. The dizygotic twinning rates of women who are twins or the sibs of twins classified by maternal age also peak at ages 35-39 but remain high at ages 40-44, then decline. It is well known that Negro women have high DZ twinning rates; a less well knwon finding is that the DZ twinning rates of Negro women also remain high after age 39. It has been suggested that high DZ twinning rates at later maternal ages may be related to a delayed age at menopause; However, published reports on age at natural menopause and analysis of our data from contemporary white US women indicate the contrary; Women who have borne unlike-sexed (DZ) twins and Negro women have a lower age at natural menopause then do white women from general populations, and a lower age in comparison with women who have borne like-sexed twins.

Adult↗

PubMed1978

Congenital heart disease in a cohort of 19,502 births with long-term follow-up.

The Child Health and Development Studies are longitudinal studies of pregnancy and the normal and abnormal development of the offspring. Women who were membres of the Kaiser Foundation Health Plan entered the study in early pregnancy, and their children were examined frequently until the youngest child in the study was 5 years old. This is a more intensive follow-up than hitherto reported. Of the 19,044 live-born children, 163 had definite and another 31 had possible congenital heart disease; the crude incidence rates per 1,000 live births were 8.8 for definite congenital heart disease and 10.4 for definite plus possible congenital heart disease. The incidence rate of congenital heart disease was 7.9 percent among all stillborn fetuses subjected to autopsy and 10.2 percent among those in this group with autopsies evaluated as being detailed enough to detect heart disease. Among the live-born children with congenital heart disease, 21 died in the neonatal period and 22 died in later infancy and childhood; about half the deaths were judged to have been due to heart disease. About 30 percent of the children with congenital heart disease had associated severe anomalies of other systems. In the whole cohort, 50 children had diagnosed chromosomal abnormalities (2.63/1,000 live births) and about 30 percent of them had congenital heart disease. Among the group of 163 children with definite congenital heart disease, the diagnosis was made in 46 percent by age 1 week, in 88.3 percent by age 1 year and 98.8 percent by age 4 years.

Abnormalities, Multiple↗

PubMed1996

Perinatal autoimmunity in offspring of diabetic parents. The German Multicenter BABY-DIAB study: detection of humoral immune responses to islet antigens in early childhood.

IDDM results from immune-mediated destruction of insulin-producing pancreatic beta-cells in individuals genetically susceptible for the disease. There is evidence that the 65-kDa isoform of GAD plays a critical role in the induction of autoimmune diabetes in NOD mice. In humans, it is still unclear when and to what beta-cell antigens autoreactive lymphocytes become activated during early disease. We conducted a prospective study from birth, BABY-DIAB, among children of mothers with IDDM or gestational diabetes or fathers with IDDM, and we investigated the temporal sequence of antibody responses to islet cells (ICA), insulin (IAA), GAD (GADA), and the protein tyrosine phosphatase IA-2/ICA512 (IA-2A). Of 1,019 children included at birth, we have currently followed 513 to the age of 9 months, 214 to the age of 2 years, and 37 to the age of 5 years. At birth, all antibody specificities were frequent in newborns of diabetic mothers but not fathers and are suggested to be transplacentally acquired because they are strongly correlated with antibody levels in their diabetic mothers. In early childhood, antibody levels were <99th percentile of control subjects in the majority of children. However, 37 children exhibited elevated antibody levels; these were most frequently detected at the age of 2 years. The antibody prevalence at age 2 years was 2.3% for ICA, 7% for IAA, 4.2% for GADA, and 2.8% for IA-2A (8.9% positive for at least one antibody). Children of diabetic fathers were positive for at least one antibody more frequently than were children of diabetic mothers (9 months of age: 8.5 vs. 3.6%; 2 years of age: 16.7 vs. 7.9%). There was no specific sequence in the appearance of positive autoantibodies, but 13 (35%) antibody-positive cases already had more than one ICA before the age of 2 years and 7 (19%) showed reactivity to three islet cell antigens before age 5 years. The presence of multiple antibodies confers high risk for the future development of diabetes; three of six children who exhibited positive antibody responses to all four antibodies tested and another child with two positive antibodies developed clinical diabetes at the ages of 13, 21, and 27 months and 5 years. We conclude that loss of tolerance to beta-cell autoantigens and appearance of autoimmune phenomena occur very early in life in individuals with genetic susceptibility for IDDM. Screening programs to identify candidates for disease-prevention therapies can therefore be focused on this young age-group, in whom the disease process may be less advanced and who may therefore be best suited to such therapies.

Animals↗

PubMed1996

Prospective follow-up study of 877 children born after intracytoplasmic sperm injection (ICSI), with ejaculated epididymal and testicular spermatozoa and after replacement of cryopreserved embryos obtained after ICSI.

A prospective follow-up study of 877 children born after ICSI was carried out. The aim of this study was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones so as to evaluate the safety of this new technique. The follow-up study included agreement to genetic counselling and prenatal diagnosis and was based on a physical examination at the Centre for Medical Genetics (Dutch-speaking Brussels Free University, Brussels, Belgium) at 2 months, 1 year and 2 years, when major and minor malformations and a psychomotor evolution were recorded. Between April 1991 and July 1995, 904 pregnancies obtained after intracytoplasmic sperm injection (ICSI) led to the birth of 877 children (465 singletons, 379 twins and 33 triplets). Prenatal diagnosis determined a total of 486 karyotypes, of which six were abnormal (1.2%) and six (1.2%) were familial structural aberrations, all transmitted from the father. This slight increase in de-novo chromosomal aberrations and the higher frequency of transmitted chromosomal aberrations are probably linked directly to the characteristics of the infertile men treated rather than to the ICSI procedure itself. In all, 23 (2.6%) major malformations were observed in the children born, defined as those causing functional impairment or requiring surgical correction. No particular malformation was disproportionately frequent. Compared with most registers of children born after assisted reproduction and with registers of malformation in the general population, the figure of 2.6% was within the expected range. These observations should be further completed by others and by collaborative efforts. In the meantime, patiens should be counselled about the available data before any treatment: the risk of transmitted chromosomal aberrations, the risk of de-novo, mainly sex chromosomal, aberrations and the risk of transmitting fertility problems to the offspring. Patients should also be reassured that there seems to be no higher incidence of congenital malformations in children born after ICSI.

Congenital Abnormalities↗

PubMed1991

Reduced amounts of cartilage collagen fibrils and growth plate anomalies in transgenic mice harboring a glycine-to-cysteine mutation in the mouse type II procollagen alpha 1-chain gene.

We have generated transgenic mice harboring a glycine-to-cysteine mutation in residue 85 of the triple helical domain of mouse type II collagen. The offspring of different founders displayed a phenotype of severe chondrodysplasia characterized by short limbs and trunk, cranio-facial deformities, and cleft palate. The affected pups died of acute respiratory distress caused by an inability to inflate lungs at birth. Staining of the skeleton showed a severe retardation of growth for practically all bones. Light microscopic examination indicated a decrease in cartilage matrix density, a severe disorganization of growth plate architecture, and the presence of streaks of fibrillar material in the cartilage matrix. Electron microscopic analysis showed a pronounced decrease in the number of typical thin cartilage collagen fibrils, distension of the rough endoplasmic reticulum of chondrocytes, and the presence of abnormally large banded collagen fibril bundles. The level of expression of the mutant type II procollagen alpha 1 chain transgene in cartilage tissues was approximately equal to that of the endogenous gene in two of the strains. We propose that the principal consequence of the mutation is a considerable reduction in density of the typical thin cartilage collagen fibrils and that this phenomenon causes the severe disorganization of the growth plate. We also postulate that the abnormal thick collagen fibrils are probably related to a defect in crosslinking between the collagen molecules. The cartilage anomalies displayed by these transgenic mice are remarkably similar to those of certain human chondrodysplasias.

Animals↗

PubMed1991

Pre-eclampsia and offspring's blood pressure, cognitive ability and physical development at 17-years-of-age.

OBJECTIVE: To investigate the influence of maternal pre-eclampsia on the blood pressure, physique and intelligence of the offspring at the age of 17 years. DESIGN: Data obtained at the age of 17 during assessment for drafting to the Israel Defence Forces and from the records of the mothers' pregnancies from the Jerusalem Perinatal Study. SUBJECTS: Study subjects were 145 girls and 283 boys whose mothers had had pre-eclampsia and controls were 12,701 girls and 20,416 boys whose mothers did not have pre-eclampsia. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure, weight, height and intelligence scores at the age of 17 were related to birthweight and the occurrence of pre-eclampsia during their mothers' pregnancies. RESULTS: Systolic blood pressure was greater than 140 mmHg in 6.9 and 11.0% of the study girls and boys, compared with 2.9 and 9.9% of the control girls and boys. The study boys but not the girls had a higher mean body mass index than the controls (P less than 0.001). There were no differences in the intelligence scores. Using multiple logistic regression to allow for the confounding effects of body mass index, weight and birthweight, the odds ratio for the risk of a systolic pressure greater than 140 mmHg was 2.30 (95% CI 1.80-4.46) for the study girls but was not significantly increased for the study boys. CONCLUSION: Maternal pre-eclampsia does not impair growth and cognitive performance in the children who reach late adolescence but may be associated with hypertension.

Adolescent↗