Maternal health during pregnancy has a direct impact on the risk and severity of neurodevelopmental disorders (NDDs) in the offspring, especially in the case of drug exposure. However, little progress has been made to assess the risk of drug exposure during pregnancy due to ethical constraints and drug use factors. We collected and manually curated sub-pathways and pathways (sub-/pathways) and drug information to propose an analytical framework for predicting drug candidates. This framework linked sub-/pathway activity and drug response scores derived from gene transcription data and was applied to human fetal brain development and six NDDs. Further, specific and pleiotropic sub-/pathways/drugs were identified using entropy, and sex bias was analyzed in conjunction with logistic regression and random forest models. We identified 19 disorder-associated and 256 regionally pleiotropic and specific candidate drugs that targeted risk sub-/pathways in NDDs, showing temporal or spatial changes across fetal development. Moreover, 5443 differential drug-sub-/pathways exhibited sex-biased differences after filling in the gender labels. A user-friendly NDDP visualization website ( https://ndd-lab.shinyapps.io/NDDP ) was developed to allow researchers and clinicians to access and retrieve data easily. Our framework overcame data gaps and identified numerous pleiotropic and specific candidates across six disorders and fetal developmental trajectories. This could significantly contribute to drug discovery during pregnancy and can be applied to a wide range of traits.
Humans ; Female ; Pregnancy ; Neurodevelopmental Disorders/metabolism* ; Male ; Prenatal Exposure Delayed Effects ; Fetal Development/drug effects* ; Drug Discovery/methods* ; Brain/metabolism*

Animals ; Caffeine/adverse effects* ; Central Nervous System Stimulants/adverse effects* ; Dose-Response Relationship, Drug ; Female ; Fetal Growth Retardation/chemically induced* ; Immune System Diseases/chemically induced* ; Male ; Organ Size/drug effects* ; Pregnancy ; Pregnancy Complications/immunology* ; Rats ; Spleen/growth & development*

Objective: To verify the health advisory for short-term exposure to phenol. Methods: The method of this validation experiment was the same as the US Environmental Protection Agency (EPA) methodology for toxicology experiments used to determine phenol drinking water equivalent level (DWEL). Pregnant female Sprague-Dawley rats were administered phenol in distilled water by gavage at daily doses of 15, 30, 60, 120, and 240 mg/kg body weight (b.w.) from implantation (the 6th day post-mating) to the day prior to the scheduled caesarean section (the 20th day of pregnancy). The following information was recorded: general behavior; body weight; number of corpus luteum, live birth, fetus, stillbirth, and implantation; fetal gender; body weight; body length; tail length; and abnormalities and pathomorphological changes in the dams. Results: In the 60 mg/kg b.w. dose group, the mortality of pregnant rats increased with increasing doses, suggesting maternal toxicity. Fetal and placental weights decreased as phenol dose increased from 30 mg/kg b.w., and were significantly different compared those in the vehicle control group, which suggested developmental toxicity in the fetuses. However, the phenol-exposed groups showed no significant change in other parameters compared with the vehicle control group ( > 0.05). Conclusion Despite using the same method as the US EPA, a different NOEAL of 15 mg/(kg·d) was obtained in this study.
Animals ; Dose-Response Relationship, Drug ; Environmental Pollutants ; toxicity ; Female ; Fetal Development ; drug effects ; Phenol ; toxicity ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Toxicity Tests, Acute

Objective: To investigate the effects of docosahexenoic acid (DHA) supplementation on infant's growth and BMI during pregnancy. Methods: A total of 1 516 healthy pregnant women delivered their babies in two maternal and child health care hospitals in Beijing and were chosen as the subjects in this cohort study from May to October 2015. Self-developed questionnaires were used to gather general information of the subjects, including age, height, weight, weight gain during pregnancy, delivery mode, DHA supplementation etc., before giving birth. Information on body length, weight, head circumference and BMI at birth and 6 months postnatal, of the infants were recorded. Breast milk was collected to test the fatty acid profiles by using the gas chromatography (GC) method at one to three months postnatally. Results: The overall rate of DHA supplementation was 47.76% among the pregnant women, in which introduction of DHA from the early and second stage of the pregnancy accounted for 49.31% and 39.64% respectively. When DHA supplementation began from the early pregnant stage, the DHA concentration showed an increase in the milk (P<0.05), whereas the supplementation began from the second and third stages did not affect the milk DHA concentration (P>0.05). Higher height and lower BMI were seen in the infants at birth and 6 months in the supplementation group when comparing to the non-supplementary group (P<0.05), with the greatest effects noticed in the earliest supplementation group. Specifically, the head circumference appeared larger from the early pregnant stage in the DHA supplementary group, than that in the non-supplement group (P=0.001). The increment of head circumference was larger than that in the other groups when the infants were 6-month old (P<0.01). Results from the partial regression analysis showed that during pregnancy, there were positive correlations between DHA supplementation and height (r=0.324, r=0.216), head circumference (r=0.221, r=0.302) as well as the increment of head circumference (r=0.276) at birth and 6 months (P<0.05). Whereas, a negative correlation was shown between DHA and the infants' BMI (r=-0.310, r=-0.371) (P<0.05) when supplementation was given during maternal pregnancy. Conclusions: When DHA supplementation program was carried out during maternal pregnancy, it could increase the height and head circumference and inhibit the rapid increase of BMI in the infants BMI. Our findings seemed helpful in promoting brain development and preventing the childhood obesity.
Body Height ; Body Mass Index ; Body Weight ; Child Development/drug effects* ; Cohort Studies ; Dietary Supplements ; Docosahexaenoic Acids/pharmacology* ; Female ; Humans ; Infant ; Infant, Newborn/physiology* ; Maternal-Fetal Exchange ; Parturition ; Pregnancy ; Pregnancy Outcome ; Prenatal Care ; Weight Gain

The study aims to investigate the embryo-fetus development toxicity of the novel PPAR-δ agonist HS060098 on SD rats. The pregnant rats that were randomly divided into the solvent control group (1% hydroxypropyl methyl cellulose water solution) and HS060098 suspension groups (10, 30 and 100 mg x kg(-1) xd(-1)) were orally administered with HS060098 suspension or vehicle during the gestation of 6 -15 days (GD6-15). At termination (GD20), female rats were sacrificed. The pregnant females were evaluated by corpora lutea count, implantation sites, existence and death of embryos. Fetal sex, weight, externals, variations and malformations of viscus and skeleton were observed. The results show that there were no significant abnormality in maternal general conditions and fetal appearance as well as viscera, but in the 100 mg x kg(-1) x d(-1) group, the maternal weight gain decreased greatly (P < 0.01) and the skeletal ossification delayed remarkably (P < 0.01); in the 30 mg x kg(-1) xd(-1) group, the fatal and litter number of incompletely ossified sternebrae II was higher than those of the control group (P < 0.05); the skeletal malformations occurred in all dose groups, which indicate that the novel PPAR-δ agonist HS060098 had maternal toxicity and adversely effected fetal skeletal development under the experimental conditions.
Animals ; Bone and Bones ; drug effects ; Embryonic Development ; drug effects ; Female ; Fetal Weight ; PPAR delta ; agonists ; Pregnancy ; Rats ; Toxicity Tests

In recent years there have been more widely and deeply studies in investigating melamine toxicity. Generally, it is believed that the main target of melamine is the urinary system. However, previous studies revealed that it also had additional biological actions. Obviously, the toxicity mechanisms of melamine have not been fully clarified. It is well known that fetus and infant periods play the most fundamental role in the brain development. And melamine can pass through the placental and blood-brain barrier, and then exerts toxic effects on the central nervous system. This article reviewed the reports about the topic in recent years, for better understanding the dangers of melamine to infants and providing experimental data for further study.
Animals ; Blood-Brain Barrier ; drug effects ; Brain ; growth & development ; Central Nervous System ; drug effects ; Cognition ; drug effects ; Female ; Humans ; Maternal-Fetal Exchange ; drug effects ; Pregnancy ; Triazines ; pharmacokinetics ; toxicity

Animals ; Cadmium Radioisotopes ; toxicity ; Female ; Fetal Development ; drug effects ; Fetus ; Maternal-Fetal Exchange ; Pregnancy ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of nonylphenol (NP) exposure on the genital development of fetal male rats in pregnant rats, and to measure the mRNA and protein expression of insulin-like factor3 (Insl-3) in the testicular tissue of fetal rats.

METHODSA total of 100 pregnant SD rats were equally assigned to blank control group and four NP treated groups. Each rat in the NP treated groups received intragastric administration of NP at doses of 5, 40, 100, or 200 mg/kg/d from day 14 to 19 of gestation, and the rats in the blank control group received intragastric administration of pure peanut oil. The pregnant rats were sacrificed on day 19 of gestation. The body weight and testicular weight of each fetal rat were measured, and the descent of testis was also observed. The mRNA and protein expression of Insl-3 in the testicular tissue of fetal rats was analyzed by reverse transcription-PCR and Western blot.

RESULTSCompared with the blank control group, the 40, 100, and 200 mg/kg NP treated groups showed significantly decreased body weight and weight coefficient of testis (P < 0.05 or P < 0.01), significantly decreased testicular descent (P < 0.05), and significantly decreased mRNA and protein expression of Insl-3 (P < 0.05 or P < 0.01).

CONCLUSIONExposure to nonylphenol can lead to testicular maldevelopment, incomplete testicular descent, and Insl-3 expression downregulation of fetal male rats in pregnant rats.

Animals ; Body Weight ; Female ; Fetal Development ; drug effects ; Insulin ; metabolism ; Male ; Maternal Exposure ; adverse effects ; Organ Size ; Phenols ; toxicity ; Pregnancy ; Proteins ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Testis ; drug effects ; embryology ; pathology

OBJECTIVETo observe the toxicity of hyperoside in rat embryo-fetal development, in order to provide preference for safe use of drugs during gestation period.

METHODHealthy pregnant rats were randomly divided into hyperosid groups (30, 175, 1000 mg x kg(-1) x d(-1)), the positive control group (cyclophosphamide, 7 mg x kg(-1) x d(-1)) and the solvent control group (1% aqueous carboxymethylcellulose). These rats were orally administered with hyperosid or vehicle during 6-15 d after gestation and subcutaneously injected with cyclophosphamide during 11-13 d. Maternal clinical sign, abortions, premature deliveries and body weight were monitored throughout gestation. At termination (gestation days 20), pregnant females were evaluated for clinical symposiums, weight change, corpora lutea count, existence and death of embryos; live fetuses were examined for gender, external, visceral and skeletal malformation and variations.

RESULTAll pregnant rats showed no significant abnormality in appearance, viscera and skeletal development. However, there was a difference between the high-dose group of hyperoside and negative control group in the fetus body weight, the length of the embryos and the length of tail (P < 0.05).

CONCLUSIONPregnant women are suggested to cautiously use hyperoside because it shows certain impact on development of fetal rats under the experimental conditions.

Abelmoschus ; chemistry ; Animals ; Drugs, Chinese Herbal ; toxicity ; Embryonic Development ; drug effects ; Female ; Fetal Development ; drug effects ; Litter Size ; drug effects ; Male ; Pregnancy ; Quercetin ; analogs & derivatives ; toxicity ; Rats ; Rats, Wistar

OBJECTIVETo investigate the potential developmental toxicity of Radix Ophiopogonis decoction in SD rats.

METHODTimed-pregnant SD rats were given Radix Ophiopogonis decoction (26.9 g x kg(-1)) or vehicle (distilled water) by gavage on gestation days 6-17. Maternal clinical sign, abortions, premature deliveries, and body weight were monitored throughout gestation. At termination (gestation days 20) pregnant females were evaluated for clinical status and gestational outcome; live fetuses were examined for gender, external, visceral and skeletal malformation and variations.

RESULTNo deaths, premature deliveries or dose-related clinical signs were attributed to Radix Ophiopogonis decoction. Maternal body weight and body weight gain were not affected. There were no effects on fetus weight and viability, incidences of fetal malformation and variation.

CONCLUSIONThese results demonstrated that Radix Ophiopogonis decoction had no detectable adverse effects in either the treated F0 female rats or the fetuses.

Animals ; Body Weight ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Embryonic Development ; drug effects ; Female ; Fetal Development ; drug effects ; Fetal Weight ; drug effects ; Humans ; Male ; Models, Animal ; Ophiopogon ; chemistry ; Pregnancy ; Random Allocation ; Rats ; Rats, Sprague-Dawley