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PubMedDate not supplied

The effects on offspring of premature parturition.

The time of parturition defines the length of the intrauterine period of fetal life, a requisite to achieve adequate adaptation to the external environment. Immaturity, a condition whose severity is inversely related to the length of pregnancy, is the main determinant of the increased morbidity and mortality associated with preterm birth. Despite great advances in medical technology and expertise, mainly after the introduction of the neonatal intensive care units, only one- to two-thirds of infants from the subsets with lower birthweight/gestational age reach survival at discharge. Distinct major neurological and sensorial sequelae, including cerebral palsy, retinopathy of prematurity, and hearing loss, as well as reduced neuropsychological abilities, leading to deficient academic achievement and deterioration of several aspects of health status, are still highly prevalent among the most immature children. Interestingly, decreasing mortality rates, which are not followed by detectable increases of disability, are being observed in recent years. Future advances may be expected from clinical and basic research on uterine contractility and cervical softening. Also, changes in reproductive technology procedures, a main factor in the incidence of multiple pregnancies, and a more refined approach to obstetric care, compose some of the clinical interventions which may reduce the problem.

Developed Countries↗

PubMedDate not supplied

[The success of maternal feeding with very low birth weight premature infants, singletons and twins: a 10-year experience].

UNLABELLED: There are very few reports about the feasibility of maternal milk feeding in very low birthweight preterm infants (VLBW), especially in twins. Therefore we conducted a cohort retrospective study to evaluate the feeding patterns of the 226 VLBW discharged from our neonatal intensive care unit from 1987 to 1996. Their gestational age was 30 +/- 2.6 weeks, birthweight 1166 +/- 224 g and they were hospitalized for 67 +/- 37 days (means +/- 1 SD). Of the 226 VLBW 49% were males, 39% had birthweight below 10 degrees centile for gestational age and 56% were born to non-residents in our area. There were 181 single births and 45 (20%) multiple births, of which 16 from pregnancies with 3 or more fetuses. Of the total cases 22% were discharged feeding maternal milk (MM) exclusively and 21% on mixed-feeding, maternal + formula milk (FM). Percentages were respectively 23% and 18% for single newborns, 11% and 29% for twins. Singletons and twins were discharged on FM with comparable percentages (59 and 60%). With passing years we have noticed a significant increase (chi square for linear trend < 0.01) for maternal milk feeding. In the last 2 years 49% of singletons and 38% of twins were discharged on MM, 14% and 24% on MM + FM, and only 37% and 38% on FM only. Between singletons and twins there were no statistically significant differences as far as feeding at discharge is concerned. CONCLUSIONS: most mothers, if correctly informed and encouraged, are able to breast-feed, exclusively or partially, their VLBW offspring, including twins, in the first months of life.

Breast Feeding↗

PubMed1975

The effects of drinking on offspring: an historical survey of the American and British literature.

Current research on the effects on offspring of drinking during pregnancy has revived interest in an extremely old topic. Observations made during England's Gin Epidemic (1720-1750) were followed by warnings of 19th-century medical writers that parental drinking could damage the fetus. Many concurring studies were reported in the medical literature from 1865 to 1920. Research interest declined during Prohibition, and authorities later discounted the previous work. Recently a relationship between maternal drinking and abnormal morphogenesis has been again described.

Abnormalities, Multiple↗

PubMed2004

Rare manifestations of sirenomelia syndrome: a report of five cases.

Five cases of sirenomelia presented with rare manifestations are discussed. Three neonates were born alive and died within 2 to 12 hours after birth. One case was the offspring of a triple in vitro fertilization pregnancy with history of early intrauterine death of one of the triplets. The main features included fusion of lower extremities (five of five), renal agenesis (three of five), polycystic renal dysplasia (two of five), anal atresia with large bowel hypoplasia (three of five), pulmonary hypoplasia (four of five), and single umbilical artery (five of five). Other features that have only rarely been associated with sirenomelia included concurrence of congenital heart disease and neuroblastoma, gallbladder agenesis, and upper extremity defects.

Abnormalities, Multiple↗

PubMed1980

A comparison of pregnancy experience in DES-exposed and DES-unexposed daughters.

Reproductive histories were compared for 226 DES-exposed and 203 -unexposed daughters whose mothers participated in a double-blind evaluation 27 years before. Irregular menstruation was slightly more common among the exposed (10%) than among the unexposed (4%). Nineteen of the exposed and only four of the unexposed had primary infertility. Among those at risk, 86% of the unexposed and 67% of the exposed had become pregnant. The reasons for these differences are not known. Comparison of evaluable first pregnancy outcome revealed full-term live birth to be more common among the unexposed (85%) than the exposed (47%). Premature live birth was experienced by 22% of the exposed but only 7% of the unexposed. Nonviable outcomes of stillbirth, neonatal death, miscarriage and ectopic pregnancy occurred in 31% of the exposed and 8% of the unexposed. The difference in pregnancy outcomes between the groups is highly significant. The DES-exposed with transverse cervicovaginal ridges were more likely to experience a nonviable outcome. Overall 82% of the exposed and 93% of the unexposed had at least one live offspring.

Abortion, Spontaneous↗

PubMed1998

Overexpression of mouse follistatin causes reproductive defects in transgenic mice.

Follistatin is an activin-binding protein that can act as an activin antagonist in vitro. Follistatin also binds heparin sulfate proteoglycans and may function as a reservoir for activins in vivo. In the mouse, follistatin mRNA is first detected in the deciduum on embryonic day 5.5 and later in the developing hindbrain, somites, vibrissae, teeth, epidermis, and muscle. We have previously shown that follistatin-deficient mice have numerous embryonic defects including shiny, taut skin, growth retardation, and cleft palate leading to death within hours of birth. To further define the roles of follistatin during mammalian reproduction and development, we created gain-of-function mutant mice in which mouse follistatin is overexpressed. The mouse metallothionein (MT)-I promoter was placed upstream of the six-exon mouse follistatin (FS) gene. To distinguish wild-type and transgenic follistatin mRNA, the 3'-untranslated region of the mouse follistatin gene was replaced with the SV40 untranslated and polyA sequences. Three male and two female founder transgenic mice were produced, were fertile, and transmitted the transgene to offspring. Northern blot analysis demonstrated that the transgene mRNA was expressed at varying levels in the livers of offspring from four of five of the transgenic lines and was expressed in the testes in all five lines. In MT-FS line 4, which had the highest expression of the transgene mRNA in the liver, the transgene transcripts were also present in multiple other tissues. Phenotypically, the MT-FS transgenic lines had defects in the testis, ovary, and hair. Mice from MT-FS lines 7 and 10 had slightly decreased testis size, whereas mice from lines 4, 5, and 9 had much smaller testes and shiny, somewhat irregular, fur. Histological analysis of the adult testes from line 5 and 9 males showed variable degrees of Leydig cell hyperplasia, an arrest of spermatogenesis, and seminiferous tubular degeneration leading to infertility. Female transgenic mice from lines 4 and 9 had thin uteri and small ovaries due to a block in folliculogenesis at various stages. Many of the line 9 female mice eventually became infertile, and all of the line 4 female mice were infertile. Suppressed serum FSH levels were seen in only the line 4 transgenic male and female mice, the line with widespread expression of the transgene. Serum FSH levels were not significantly different in gonadectomized wild-type and line 5 transgenic male mice despite high levels of the follistatin transgene mRNA in the liver of these transgenic mice. These results suggest that follistatin exerts its effects at the levels of the gonads and pituitary as a local regulator of activin and possibly other transforming growth factor-beta family members.

Animals↗

PubMed2006

Phenotypic abnormalities observed in aged cloned mice from embryonic stem cells after long-term maintenance.

Somatic/embryonic stem cell cloning has made it possible to produce an individual genomically identical to another individual. However, the cloned animals have a variety of abnormalities caused by the aberrant gene modification, with insufficient reprogramming in cloning. We previously reported abnormalities in cloned mice at birth. In this study, we examined what abnormalities could be seen in cloned mice after long-term maintenance. The aged cloned mice showed multiple abnormalities: increase of body weight, some phenotypic abnormalities in the kidneys, testes and thymus, and lower urea nitrogen in their serum biochemical values. The kidneys of all cloned mice were hypertrophied, with a metamorphic or whitish appearance. The multiple lesions, including the enlarged renal pelvis and distension of the renal veins in histology, might be the result of urine accumulation by urinary tract obstruction. The testes of the cloned mice were atrophied, and showed no sperm formation in histology. In contrast, the thymus was rather hypertrophied, and a comparably increased number of lymphocytes were observed in the medulla, consisting mainly of T cells. By conducting a progeny test between the cloned mice, it was confirmed that these abnormalities in the aged cloned mice were not transmitted to their offspring, indicating that the incomplete reprogramming in clones might be in part responsible for the abnormalities detected in aged clones. These results indicate that the postnatal abnormalities observed in aged cloned mice are varied and can be restored through the germ line.

Aging↗

PubMed2002

A deficient maternal calcium intake during pregnancy increases blood pressure of the offspring in adult rats.

OBJECTIVE: To assess in an animal model the effect of maternal dietary calcium intake during pregnancy on the blood pressure of offspring. DESIGN: Randomised controlled trial. SAMPLE: Ninety-eight 20-week-old female Wistar-Kyoto rats, giving birth to a total of 119 pups that were included in the follow up study. METHODS: Rats were randomised to a calcium deficient diet, a diet with the recommended calcium levels, or a diet with calcium content much higher than the recommended levels. After one month on the experimental diet they were bred. After birth, systolic blood pressure in the offspring was measured monthly till 52 weeks of age. MAIN OUTCOME MEASURES: Blood pressure of the offspring. RESULTS: The difference in blood pressure of the offspring between the normal and low maternal calcium group increased 0.49 mmHg per month (95% CI 0.18 to 0.84), 0.38 (0.07 to 0.68) between the low and high calcium group, and 0.12 (-0.20 to 0.43) between the normal and high calcium group. At the end of the follow up (52 weeks of age) blood pressure of the offspring in the deficient calcium group was 12.1 mmHg (95% CI 8.8 to 15.4, P < 0.0001) higher than in the normal calcium group and 7.5 mmHg (95% CI 4.4 to 10.5, P < 0.001) higher than the high calcium group. Blood pressure of the offspring in the high calcium group was 4.3 mmHg (95% CI 1.0 to 7.5, P = 0.01) higher than in the normal calcium group. In a multiple regression model maternal calcium intake during pregnancy was the strongest predictor of blood pressure of the offspring during adulthood. CONCLUSIONS: This experiment supports previous studies in humans suggesting a link between calcium intake during pregnancy and blood pressure in the offspring, and provides an animal model to explore the mechanisms involved in such association.

Animals↗

PubMedDate not supplied

Effects of perinatal loratadine exposure on male rat reproductive organ development.

Normal pre- and postnatal male reproductive development and function is dependent upon testicular androgen production and is sensitive to antiandrogenic perturbations. It was of interest to determine if the H(1) histamine antagonist loratadine had the potential to alter androgen-mediated reproductive development in the rat, a sensitive species for detecting antiandrogenic effects. Loratadine was administered orally by gavage to pregnant Sprague-Dawley rats at doses of 4, 12 or 24 mg/kg from gestation day 7 to postnatal day 4, encompassing the period of androgen-dependent male reproductive development. Vehicle control rats received 0.4% aqueous methylcellulose. Dams were allowed to deliver naturally and rear their offspring until postnatal day 21. On postnatal day 21 male offspring were retained for further evaluation of androgen-dependent endpoints and the female offspring were euthanized and their sex confirmed internally. Males were necropsied from postnatal day 72 to 85. Dams administered 24 mg/kg of loratadine exhibited a transient 45% decrement in maternal body weight gain at the initiation of dosing (gestation days 7-9). Mean pup body weight on postnatal days 1 and 4 were approximately 4% lower than controls. No other effects on offspring growth were observed. Anogenital distance on postnatal day 1 was unaffected by loratadine exposure. Loratadine exposure did not induce the retention of nipples in male rats, affect preputial separation, or induce external malformations, including hypospadias. Seminal vesicle and prostate weights were not decreased by loratadine exposure. These data clearly demonstrate that systemic loratadine exposure, in multiples up to 26 times clinical exposure levels, does not exhibit in vivo antiandrogen activity, as evidenced by the absence of alterations or malformations in androgen-dependent reproductive tissues in male rats exposed to loratadine during the critical period of androgen-dependent development.

Androgens↗

PubMedDate not supplied

Counseling patients exposed to ionizing radiation during pregnancy.

Health physicists and knowledgeable clinicians have the responsibility to counsel women of reproductive age about the reproductive risks of ionizing radiation exposure before conception or during pregnancy. It is important to realize that lay individuals have many misconceptions about the reproductive risks of ionizing radiation. Many patients who have already had or will undergo some type of radiological test are apprehensive about the reproductive and developmental risks of diagnostic radiological procedures. Epidemiological studies and animal studies indicate that high exposures of ionizing radiation can cause miscarriage, congenital malformations, growth retardation, stillbirth, and cancer. With the exception of cancer, there are threshold exposures for those outcomes, with exposures below certain radiation doses not increasing the reproductive or developmental risks. The threshold exposure for birth defects at the most sensitive stage of development is 0.2 Gy, and the threshold for growth retardation and miscarriage is even higher. However, embryonic loss can occur from low exposures during the preimplantation and presomite stages of development ("the all or none period"). This is a stage when the embryo is more likely to die than survive malformed. The most sensitive period for the induction of mental retardation is from the 8th week to the 15th week of gestation. The threshold for deterministic effects increases after early organogenesis and also as the exposure is protracted, e.g., with radionuclides or multiple radiological procedures. Awareness that the threshold dose for developmental effects increases as the fetus develops complicates counseling because we do not have definitive data on threshold exposures at all stages of gestation. Ionizing radiation exposures prior to pregnancy represent a very low risk for the increased incidence of genetic disease in the offspring of the parents who have had radiation exposures to the ovary or testes. Counseling patients requires knowledge of embryology, genetics, radiation teratology, and the principles of teratology in order for the counselor to provide sympathetic, accurate, scholarly advice.

Abnormalities, Radiation-Induced↗

PubMed1975

Offspring of subfertile parents. A preliminary survey.

This preliminary survey reports findings among offspring of subfertile parents. Combining neonatal death, low birth weight and major anomalies, 11 of 60 livebirths (18%) were affected, indicating that subfertility adversely influences neonatal morbidity and mortality. Information was available for 49 of 56 children and there were none with developmental delay nor was there an increase in malformations or minor behavioral or learning disorders. Although numbers are small, these observations suggest that children of subfertile parents who survive the neonatal period do not differ from the normal population.

Adolescent↗

PubMed2026

Mechanisms of Hexavalent Chromium-Induced Reproductive Toxicity: A Focus on the Ovary and Placenta.

Hexavalent Chromium (Cr(VI)) is a Group A carcinogen, mutagen, and teratogen. Cr(VI) has been used by more than 50 industries, and its contamination of drinking water is widespread across the United States (U.S.). Epidemiological data of women who lived in Willits, California, U.S., indicate that environmental exposure to Cr(VI) adversely affects pregnancy outcomes and the health of their immediate offspring, resulting in a low birth rate, pregnancy loss, and spontaneous abortion, and their children (F1 offspring) experienced birth defects. However, the molecular mechanisms behind Cr(VI)-induced reproductive and developmental toxicity are poorly understood. Cr(VI) enters cells through anion transporters and is rapidly reduced to Cr(III) by endogenous antioxidants within the cell. Cr(III) forms adducts with DNA, which can block DNA replication and transcription; abnormal repair can lead to DNA double-strand breaks, mutations, micronucleus formation, chromosomal abnormalities, and increased genomic instability. Cr(VI) induces oxidative stress via the Fenton reaction, generating free radicals, and depleting antioxidants, thereby promoting apoptosis via p53-dependent and independent pathways, resulting in follicular atresia and accelerated reproductive aging. Antioxidant supplementation with resveratrol, vitamin C, and edaravone mitigates Cr(VI) toxicity in the ovary. Cr(VI) disrupts meiosis in metaphase II oocytes by causing DNA strand breaks, altering F-actin dynamics, disturbing microtubules, and leading to chromosome missegregation. Gestational exposure to Cr(VI) also disrupts placental function through multiple mechanisms by targeting trophoblast lineages. The current review focuses on genotoxicity, oxidative stress, and other mechanisms by which Cr(VI) disrupts the female reproductive and endocrine systems, with particular emphasis on the ovary and placenta.

Hexavalent chromium↗

PubMed1995

[Steinert's disease and pregnancy. A case report and recent literature].

Steinert's disease or myotonic dystrophy is a heredo-degenerative neuroendocrinal dystrophy. It is an autosomal dominant disorder. The arising of a congenital myotonic dystrophy of one of the new-born children of the maternity hospital enabled to diagnose the Steinert's disease of his mother. A review of the international literature enabled us to recall its interactions with pregnancy. There is an aggravation of myotonia and multiple obstetric complications such as miscarriage, premature onset of labor, polyhydramnios, stillbirth, difficulties during the evacuation, atonic postpartum hemorrhage, anesthetic-accidents. The congenital variant of myotonic dystrophy (6 to 30% of the cases) is a severe disease with a high mortality. It is only seen in the offspring of mothers who themselves have myotonic dystrophy. The myotonic dystrophy gene has been isolated and the mutation-causing myotonic dystrophy was found to result from a series of trinucleotide (CTG) repeats located in the 3' untranslated region of the gene. The direct diagnosis is henceforth possible both on the fetus and parents. Steinert's disease and its association with pregnancy are rare, especially when the affected parent has hypogonadism. The diagnosis of the congenital form is difficult because of the mother is unaware of the disorder. Family and personal history may give hints: hydramnios, appearance delay and reduced fetal movements, and the association at birth of generalized hypotonia with neonatal respiratory distress.

Adult↗

PubMed2001

A single institutional experience with 43 pregnancies in essential thrombocythemia.

OBJECTIVES: We describe the periconception circumstances and outcome of 43 consecutive pregnancies in an unselected group of young women with essential thrombocythemia (ET). PATIENTS AND METHODS: We retrospectively studied 74 consecutive cases of young women with ET seen at our institution, among whom 43 pregnancies occurred in 20 patients. RESULTS: Of the 43 pregnancies, 22 (51%) were successful (21 term and 1 preterm live births) and 21 (49%) ended in miscarriages (1 ectopic pregnancy, 2 elective abortions, 16 first-trimester spontaneous abortions, 1 stillbirth at 22 wk, and 1 abruptio placentae at 33 wk). Management of ET at the time of conception included either no specific therapy (16 cases) or the use of aspirin alone (24 cases), a cytoreductive agent (2 cases), or heparin (1 case). There were no significant differences with respect to platelet count or the effect of treatment with aspirin, either at the time of conception or during the first trimester, among cases of successful pregnancies (22), all miscarriages (21), or first-trimester spontaneous abortions (16). The findings were similar when the analysis was restricted to only first-time pregnancies. In patients with multiple pregnancies, the outcome of a subsequent pregnancy was not predicted by the outcome of the first. In general, in successful cases the last two trimesters were mostly uneventful, with healthy offspring being reported in all cases. CONCLUSIONS: Pregnant patients with ET have an increased risk of first-trimester abortion which is not predictable by preconception platelet count or aspirin therapy. In addition, our experience does not support the use of prophylactic platelet apheresis during delivery.

Abortion, Induced↗

PubMed2001

Perinatal outcome of pregnancy after GnRH antagonist (ganirelix) treatment during ovarian stimulation for conventional IVF or ICSI: a preliminary report.

BACKGROUND: Gonadotrophin-releasing hormone (GnRH) antagonists have been proven safe and effective, with no adverse effects on offspring in animal studies. Careful study of pregnancy outcome in humans is mandatory. METHODS AND RESULTS: This preliminary report includes follow-up data of patients treated with the GnRH antagonist, ganirelix, during ovarian stimulation for IVF or ICSI. In total, 333 patients were randomized in a multicentre, double-blind, dose-finding study of ganirelix, at six different doses ranging from 0.0625 to 2 mg. In total, 68 vital intrauterine pregnancies were established that resulted in the birth of 46 singletons, 12 twins and one triplet. Follow-up of the 67 pregnant patients (one subject was lost to follow-up) revealed six miscarriages (9%). Of the 61 subjects with an ongoing pregnancy, two with a singleton pregnancy did not give birth to a live-born infant (one spontaneous abortion in week 19, and one intrauterine death in week 27). The mean gestational age was 39.4 weeks for singleton pregnancies, and 36.6 weeks for multiple pregnancies. In total, 73 infants (33 boys, 40 girls) were born. A birth weight <2500 g was reported for 8.7% and 54.2% of the infants resulting from singleton and twins delivery respectively. One major congenital malformation was diagnosed; a boy with Beckwith-Wiedemann syndrome (exomphalos and macroglossia). Seven minor malformations were reported among five infants. CONCLUSIONS: In this first follow-up study, the incidence of adverse obstetrical and neonatal outcome was comparable with reported incidences for IVF-embryo transfer pregnancies.

Adult↗

PubMed2005

Teenage children of teenage mothers: psychological, behavioural and health outcomes from an Australian prospective longitudinal study.

In many industrialised countries teenage pregnancy and teenage parenthood have in recent years been identified as social and public health problems that need to be tackled. A number of studies have looked at various outcomes for teenage mothers and their offspring, and many report a strong association with poverty for the mother both before and after having a child. Few studies, however, adequately control for socioeconomic circumstances when examining health and related outcomes. Most studies have focused on perinatal outcomes in the offspring with few looking at later health and development. In Australia, where the rate of teenage pregnancy is relatively high compared to other comparable countries, teenage pregnancy is a not prominent policy concern. As such, Australia offers the opportunity to study the outcomes of teenage parenthood in a country where there may be less stigma than in countries that portray teenage parenthood as a major health and/or social problem. This paper reports findings from the Mater-University Study of Pregnancy (MUSP) and its outcomes, a prospective study of women, and their offspring, who received antenatal care at a major public hospital (Mater Misericordiae Hospital) in South Brisbane, Australia, between 1981 and 1984. We have examined the associations of maternal age (< or =18 years (n=460) versus >18 years (n=4800)) at first antenatal visit with offspring psychological, behavioural and health characteristics when the offspring--the teenage children of teenage mothers--were aged 14 years. Multiple logistic regression was used to determine the effect of maternal and family characteristics on associations between maternal age and childhood outcomes at age 14. Results show that the 14 year old offspring of mothers who were aged 18 years and younger compared to those who were offspring of older mothers were more likely to have disturbed psychological behaviour, poorer school performance, poorer reading ability, were more likely to have been in contact with the criminal justice system and were more likely to smoke regularly and to consume alcohol. However, maternal age was not associated with health outcomes in their offspring at age 14 years. Indicators of low socioeconomic position and maternal depression were also associated with poorer psychological, cognitive and behavioural outcomes among 14 year olds. In addition children from poorer socioeconomic backgrounds and whose mothers were depressed were more likely to have self-reported poor health, asthma, to have been admitted to hospital twice or more since birth and to be bed-wetters at age 14. The associations between maternal age and psychological distress, school performance, and smoking and alcohol use were all largely explained by socioeconomic factors, maternal depression, family structure and maternal smoking. These findings confirm that not all teenage mothers and their offspring have adverse outcomes, and that many if not the majority have good outcomes.

Adolescent↗

PubMed2004

Multiple effects of theobromine on fetus development and postnatal status of the immune system.

Caffeine and its active derivative, theobromine, are probably the most frequently ingested pharmacologically active substances. Considering their uninhibited transport via the placental barrier as well as immature enzymatic activities and metabolic pathways in embryos and infants resulting in the longer half-life of methyloxanthines and their accumulation, unrestrained uptake of these substances might result in noticeably more pronounced biological effects during pregnancy and the postnatal period. Our previous studies have shown that methyloxanthines are significant inhibitors of angiogenic growth factors production and angiogenesis itself. We have hypothesized that increased uptake of these substances might affect embryonal angiogenesis and, later in the postnatal period, maturation and functional activity of the offspring's immune system. The study was performed on 2-month-old Balb/c mice fed theobromine 2 or 6 mg/day during pregnancy and lactation. On day 18 of pregnancy the number and weight of embryos were assessed as was their tissue angiogenic activity, using the cutaneous angiogenesis assay. In the group of 4-week-old sucklings, body and spleen were weighed together with the trunk, and tail and limb length were measured. Six weeks after birth the splenocytes' mitogen-induced activity and their ability to induce graft-versus-host reaction as well as the humoral response to SRBC antigen were evaluated. Content of theobromine in the embryos' tissue was estimated by high liquid performance chromatography (HPLC). Theobromine feeding resulted in significant inhibition of embryo growth as assessed by their weight and decreased angiogenic activity of their tissue. The theobromine content in embryo tissue from treated groups was higher than in the controls, and the difference was close to significant. In the postnatal period the discrepancies in the treated 4-week-old group's development were also observed in the significantly shorter limbs in comparison to the controls. Moreover in the treated group of 6-week-old sucklings, considerable variations in the immune system's functional activity were registered as far as cellular and immune response were concerned. Respectively, the splenocytes' mitogen-induced proliferative activity was significantly suppressed while the graft-versus-host reaction was up-regulated, and the serum antibodies titer was elevated in correspondence to the observed spleen enlargement. We concluded that a theobromine-enriched diet affects progeny development in both prenatal and postnatal periods. Consequently, particular attention should be paid to the reduction of theobromine consumption, and most probably that of other methyloxanthines, during pregnancy and lactation.

Angiogenesis Inhibitors↗

PubMed2004

Prenatal glucocorticoid exposure alters hypothalamic-pituitary-adrenal function and blood pressure in mature male guinea pigs.

Pregnant guinea pigs were treated with dexamethasone (1 mg kg(-1)) or vehicle on days 40-41, 50-51 and 60-61 of gestation, after which animals delivered normally. Adult male offspring were catheterized at 145 days of age and subjected to tests of hypothalamic-pituitary-adrenal (HPA) axis function in basal and activated states. Animals exposed to dexamethasone in utero (mat-dex) exhibited increased hippocampus-to-brain weight ratio, increased adrenal-to-body weight ratio and increased mean arterial pressure. There were no effects on gestation length, birth weight and postnatal growth. There were no overall differences in diurnal plasma adrenocorticotropic hormone (ACTH) and cortisol profiles, though there were subtle differences during the subjective afternoon between control and mat-dex offspring. A significant decrease in initial ACTH suppression was observed following dexamethasone injection in mat-dex offspring compared to control offspring. Molecular analysis revealed significantly increased MR mRNA expression in the limbic system and particularly in the dentate gyrus in mat-dex offspring. In the anterior pituitary, both pro-opiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA levels were significantly elevated in mat-dex offspring. In conclusion, (1) repeated prenatal treatment with synthetic glucocorticoid (sGC) permanently programmes organ growth, blood pressure and HPA regulation in mature male offspring and these changes involve modification of corticosteroid receptor expression in the brain and pituitary; (2) the effects of prenatal sGC exposure on HPA function appear to change as a function of age, indicating the importance of investigating HPA and cardiovascular outcome at multiple time points throughout life.

Adrenal Cortex↗