• Toxicological Research
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• 제16권3호
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• pp.229-238
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• 2000

The purpose of reproductive toxicity studies is to evaluate all effects resulting from paternal or maternal exposure that interfere with conception, development, birth, and maturation of offspring. In 1966, the US Food and Drug Administration (US FDA) published guidelines for a three-segment study for drug testing to examine adverse effects on fertility and pregnancy. Three segments were proposed: Segment I, Study of Fertility and General Reproductive Performance, to provide information on breeding, fertility, nidation, parturition, neonatal effects and lactation: Segment II, Teratological study, to provide information on embryo toxicity and teratogenicity: and Segment III. perinatal and Postnatal Study, to provide information on late fetal development, labour and delivery, neonatal viability, and growth and lactation. The classic guideline is still used to this day with only monor modification throughout the world. In the present review, the principles and methods of reproductive toxicity studies are discussed with special attention given to scientific issues.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.116-116
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• 2003

2-Bromopropane (2-BP), a halogenated propane analogue, is a substitute for chlorofluorocarbones (CFCs) which have a great potential to destroy the ozone layer and to warm the earth's environment. The present study was undertaken to evaluate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure during the gestational days (GO) 6 through 17 in ICR mice.(omitted)

• Toxicological Research
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• 제22권2호
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• pp.127-133
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• 2006

Recently, we have reported that the environmental pollutant 2-bromopropane (2-BP) induces a significant embryo-fetal developmental toxicity in rats. However, the cause of developmental toxicity and the relationship between maternal and developmental toxicities could not be elucidated because the developmental toxicity of 2-BP was observed only in the presence of maternal toxicity The in vitro teratogenicity study using whole embryo culture was carried out to understand the teratogenic properties and the possible mechanism of teratogenicity induced by 2-BP in rats. Rat embryos aged 9.5 days were cultured in vitro for 48 hrs at medium concentrations of 0, 1, 3, or 10 mg/ml of 2-BP. Embryos were evaluated for growth, differentiation, and morphological alterations at the end of the culture period. At 10 mg/ml, 2-BP caused a delay in the growth and differentiation of embryos and an increase in the incidence of morphological alterations, including altered yolk sac circulation, abnormal axial rotation, craniofacial hypoplasia, open neuropore, absent optic vesicle and kinked somites. At 3 mg/ml, only a delay in the growth and differentiation of embryos was observed. There were no adverse effects on embryonic growth and development at the concentration of 1 mg/ml. The results showed that the exposure of 2-BP to rat embryos results in a developmental delay and morphological alterations at dose levels of 3 mg/ml culture media or higher and that 2-BP can induce a direct developmental toxicity in rat embryos.

• 대한수의학회지
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• 제43권4호
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• pp.657-666
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• 2003

The present study was undertaken to evaluate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure during the gestational days (GD) 6 through 19 in Sprague-Dawley rats. The test chemical was administered subcutaneously to pregnant rats at dose levels of 0, 375, 750 and 1250 mg/kg/day. During the test period, clinical signs, mortality, body weights and food consumption were examined. All dams were subjected to caesarean section on GD 20 and their fetuses were examined for external, visceral and skeletal abnormalities. At above 750 mg/kg, toxic effects including signs of toxicity, suppressed body weight, decreased gravid uterine weight and reduced food intake were observed in pregnant dams. An increase in the fetal deaths, a decrease in the litter size, a reduction in the fetal body weight and an increase in the incidence of fetal morphological alterations were also found. There were no adverse effects on either pregnant dams or embryo-fetal development at a dose level of 375 mg/kg. These results suggest that a 14-day subcutaneous dose of 2-BP is embryolethal and teratogenic at above 750 mg/kg/day in pregnant rats. In the present experimental condition, the no-observed-adverse-effect level of 2-BP is considered to be 375 mg/kg/day for dams and embryo-fetuses, respectively.

• Neonatal Medicine
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• 제28권3호
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• pp.124-132
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• 2021

Purpose: Neonatal near miss (NNM) allows for the detection of risk factors associated with serious newborn complications and death, the prevention of which could reduce neonatal mortality. This study was conducted with the objective of identifying predictors for NNM in a tertiary hospital in Bangalore city. Methods: This was an unmatched case-control study involving 120 NNM cases and 120 controls. NNM was determined using Pileggi-Castro's pragmatic and management criteria. Data was collected from in-patient hospital records and interviews of postpartum mothers. Multiple logistic regression of exposure variables was performed to calculate adjusted odds ratio (AOR) with 95% confidence interval (CI). Results: Significant predictors were maternal age ≥30 years (AOR, 5.32; 95% CI, 1.12 to 9.29; P=0.041), inadequate antenatal care (ANC) (AOR, 8.35; 95% CI, 1.98 to 51.12; P=0.032), <3 ultrasound scans during pregnancy (AOR, 12.5; 95% CI, 1.60 to 97.27; P=0.016), maternal anaemia (AOR, 18.96; 95% CI, 3.10 to 116.02; P=0.001), and any one obstetric complication (hypertensive disorder in pregnancy, diabetes in pregnancy, preterm premature rupture of membranes, prolonged labour, obstructed labour, malpresentation) (AOR, 4.34; 95% CI, 1.26 to 14.95; P=0.02). Conclusion: The predictors of NNM identified has important implications for public health policy and practice whose modifications can improve NNM. These include expanding essential ANC package to include ultrasound scans, ensuring World Health Organization recommendations of eight ANC visits, capacity building at all levels of health care to strengthen routine ANC and obstetric care for effective screening, referral and management of obstetric complications.

• Clinical and Experimental Pediatrics
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• 제65권2호
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• pp.85-89
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• 2022

Background: There is evidence of a relationship between prenatal excess androgen exposure and central nervous developmental problems and attention-deficit/hyperactivity disorder (ADHD) in the offspring of mothers with polycystic ovary syndrome (PCOS). Purpose: Here we aimed to use a meta-analysis to investigate whether the offspring of mothers with PCOS are at an increased chance of developing ADHD. Methods: Three main English databases were searched for articles published through December 2020. The Newcastle-Ottawa Scale was used to assess study quality. Study heterogeneity was determined using I² statistics and publication bias was assessed using Begg and Egger tests. The results are presented as odds ratio (OR) and relative ratio (RR) estimates with 95% confidence intervals (CIs) using a random-effects model. Results: Six articles (3 cohort and 3 case-control studies; 401,413 total ADHD cases) met the study criteria. Maternal PCOS was associated with an increased risk of ADHD in the offspring based on OR and RR (OR, 1.42; 95% CI, 1.27-1.57) and (RR, 1.43; 95% CI, 1.35-1.51), respectively. There was no heterogeneity among the included articles based on OR (I²=0.0%, P=0.588) and RR (I²=0.0%, P=0.878). Conclusion: Our study showed that maternal PCOS is a risk factor for ADHD. Therefore, screening their offspring for ADHD should be considered part of the comprehensive clinical care of women with PCOS.

• 한국발생생물학회지:발생과생식
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• 제4권1호
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• pp.95-100
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• 2000

환경에 방출되어 있는 많은 내분비교란물질들은 사람과 동물의 내분비계에 교란을 일으킬 수 있는 잠재력을 가진다. 뇌의 성분화는 생식소 호르몬 영향하에 비가역적으로 진행되며 흰쥐의 경우 이 시기는 임신말기에서 생후 7∼10일 가량이다. 최근에 본 연구진은 횐쥐의 뇌 성 분화의 결정적인 시기에 발현되는 KAP3유전자를 클로닝하였다 (Choi ＆ Lee, 1999). KAP3의 기능은 신경세포를 포함한 세포에서 aronal tansport를 조절하는 것으로 알려져 있다. 본 연구에서는 흰쥐 뇌 발생의 결정적인 시기에 내분비 교란물질인 Dichlorodiphenyl trichloroethane (DDT)가 KAP3유전자 발현과 성분화에 미치는 영향을 검토하였다. DDT에 노출된 임신 17일된 흰쥐 태아 암컷과 수컷의 뇌에서 KAP3 mRNA의 발현이 증가하였다. 그러나 출생후 DDT에 노출된 흰쥐 암컷과 수컷의 뇌에서는 KAP3 mRNA의 발현은 감소하였다. 또한 태어난 직후 DDT에 노출된 경우 체중이 현저히 감소하였으며 수정율도 DDT에 노출되지 않은 흰쥐에 비하여 크게 낮았다. 이러한 결과는 내분비 교란물질인 DDT가 뇌의 성 분화와 관련된 유전자인 KAP3의 전사에 영향을 미치며, 내분비 교란물질에 노출된 태아의 뇌 분화에서 독성을 보이는 것을 의미한다. 그리고 KAP3유전자는 동물의 신경세포의 발생에 미치는 내분비 교란 물질의 독성을 분자생물학적으로 연구하기 위한 유전자 지표로도 사용 가능하다고 생각된다.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제17권1호
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• pp.40-50
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• 2006

연구목적 : 본 연구는 성학대 피해 아동에게서 나타나는 성행동을 분석하고, 인구학적인 변인, 가족변인, 성학대 피해 특성의 관련성에 대해 알아보고자 하였다. 방 법 : 성학대 피해가 확인된 2-13세 이하의 아동 121명을 대상으로 하였다. 아동성행동척도(CSBI)와 소아우울척도, 소아불안척도 및 한국 부모용 아동 청소년 행동평가 척도가 실시되었다. 각 척도의 점수와 성학대 사건의 특성, 인구통계학적인 변인, 가족 변인 등에 따른 차이 검증과 상관분석이 이루어졌다. 결 과 : 분석결과, CSBI점수가 3세경에 정점을 이루었다가 점차 감소하는 양상을 보였다. $2{\sim}5$세 집단에서 비교적 가벼운 신체 접촉과 자위 및 성기노출의 시인빈도가 높았다. 물건으로 자위를 하거나 항문 속에 물건을 넣는 등의 명백히 부적절한 성적 행동이 $2{\sim}11%$에서 보고되었는데, 대부분 5세 미만의 아동에서 나타났다. 성학대 사건의 특징 중 가해자와의 면식이 있는 집단에서 CSBI 점수가 의미 있게 높게 나타났으며(p<.05), 음경의 질 삽입이나 가해자의 성기 노출이 있었던 경우에도 CSBI 점수가 의미 있게 높게 나타났다(p<.05). 어머니의 학력이 대졸 이상인 집단에서 CSBI 점수가 의미 있게 높았고(p<.05) 양친부모가 모두 있는 가정의 아동보다는 편부 편모 및 조부모나 기타 사람들에게서 양육되는 집단의 아동에서도 CSBI 점수가 의미 있게 증가되는 양상을 드러내었다(p<.05). 결 론 : 연령이 낮을수록, 가해자가 면식이 있는 사람일수록, 음경의 질 삽입이 있거나 가해자의 성기에 노출되었을수록, 어머니의 교육 수준이 대졸 이상일수록, 그리고 아동의 심리적 지지체계가 부족할수록 보다 많은 성행동을 보이는 것으로 나타났다. 또한, 보호자의 정서적인 상태와 성격특성도 성행동의 증가에 의미 있는 영향을 미치는 것으로 나타났다. 본 연구의 함의와 제한점, 및 추후 연구의 방향에 대해 논의하였다.

• Toxicological Research
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• 제24권4호
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• pp.263-271
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• 2008

Recently we reported that 2-bromopropane (2-BP) has maternal toxicity, embryotoxicity, and teratogenicity in Sprague-Dawley rats. The aims of this study are to examine the potential effects of 2-BP administration on pregnant dams and embryo-fetal development, and to investigate the effects of metabolic activation induced by phenobarbital (PB) on developmental toxicities of 2-BP. Pregnant rats received 1000 mg/kg/day subcutaneous 2-BP injections on gestational days (GD) 6 through 10 (Group II and Group IIII) or 11 through 15 (Group IV). Pregnant rats in Group III received an intraperitoneal PB injection once daily at 80 mg/kg/day on GD 3 through 5 for induction of the liver metabolic enzyme system. Control rats received vehicle injections only on GD 6 through 15. All dams underwent caesarean sections on GD 20 and their fetuses were examined for external, visceral, and skeletal abnormalities. Significant adverse effects on pregnant dams and embryo-fetal development were observed in all the treatment groups, and the maternal and embryo-fetal effects of 2-BP observed in Group II were higher than those seen in Group IV. Conversely, maternal and embryo-fetal developmental toxicities observed in Group III were comparable to those seen in Group II. These results suggest that the potential effects of 2-BP on pregnant dams and embryo-fetal development are more likely in the first half of organogenesis (days $6{\sim}10$ of pregnancy) than in the second half and that the metabolic activation induced by PB pre-treatment did not modify the developmental toxic effects of 2-BP in rats.

• Biomolecules & Therapeutics
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• 제20권2호
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• pp.226-233
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• 2012

Ethanol exposure during gestational period is related to growth retardation, morphological abnormality, and even in neurological abnormalities including attention deficit/hyperactivity disorder (ADHD)-like behaviors on offspring. However, relatively little is known about the effects of maternal ethanol consumption prior to conception on their offspring. In this study, we investigated whether maternal ethanol administration during preconceptional phase produces ADHD-like behaviors in the rat offspring. Sprague-Dawley (SD) female rats were administrated ethanol via intragastric intubation with dosing regimen of 6 g/kg daily for 10 consecutive days and treated female rats then mated with non-treated male SD rats after 8 weeks. Another group subjected to the same procedure as those conducted on ethanol treated group except the saline administration instead of ethanol. Offspring was tested for their ADHD-like behaviors using open field test, Y maze test and impulsivity test that is performed in the aversive electronic foot shock paradigm. Offspring of preconceptional ethanol treated (EtOH) group showed hyperlocomotive activity, attention deficit and impulsivity. And reduction of striatal dopamine transporter (DAT) level was observed by Western blot in the EtOH group, compared to control (Con) group, while the immunohistochemical analysis exhibited increased expression of norepinephrine transporter (NET) in the frontal cortex. These results suggest that maternal ethanol consumption in the preconceptional phase induces ADHD-like behaviors in offspring that might be related to the abnormal expression of DAT and NET in rat.