A matter of insulin: Developmental programming of body weight regulation

Alterations of the intrauterine and early postnatal nutritional, metabolic and hormonal environment may cause a predisposition for disorders and diseases throughout later life. Studies in offspring of diabetic mothers (ODM) have decisively contributed to this perception and our understanding of causal mechanisms. Hormones in particular are environment-dependent organizers of the developing organism. When they are present in non-physiological concentrations during critical periods of early development, they can dose-dependently lead to a permanent malprogramming of fundamental regulatory systems. Worthy of note, fetal and neonatal hyperinsulinism is the pathognomic feature in ODM. Epidemiological, clinical, as well as experimental data obtained by our group during the past two decades indicate that insulin itself, when occurring in elevated concentrations during perinatal life, may program the development of obesity and diabetes. Similarly, this may occur due to general increase of fetal food supply, e.g., in overweight pregnant women and neonatal overfeeding. From a clinical point of view, universal screening and therapy for all types of diabetes during pregnancy as well as avoidance of early postnatal overfeeding, especially by promoting breast feeding, are, therefore, recommended. These measures might serve as causal approaches to a genuine primary prevention.     

Effect of vitrification of mouse oocyte on the behavior of adult offspring

Objective

To evaluate the effect of vitrification of mouse oocytes on the behavior of adult offspring.

Study design

Oocytes from mice were vitrified, warmed and inseminated, and two-cell embryos were transferred to foster mothers. The behavioral characterization of the offspring was detected by the Morris water maze test, forced swimming test, and elevated plus maze test, and compared to that of offspring from fresh oocytes.

Results

Offspring produced by vitrified oocytes showed normal motor function. In the Morris water maze test of spatial learning there was a slightly decreased time spent in the quadrant containing the platform relative to mice from fresh oocytes, but the difference did not reach statistical significance. In addition, offspring from vitrified oocytes did not exhibit alterations in emotional behavior.

Conclusion

No alterations were found in the behavioral characterization of adult offspring from vitrified oocytes compared with those from fresh oocytes.     

Obesity and age at menarche

A cohort study of 3,169 girls born in April 1984-April 1987 in Odense and Aalborg, Denmark, was performed to examine whether maternal prepregnancy body mass index (BMI) accounted for daughter's age of menarche (AOM) and, if so, whether it accounted for part or all of the association between daughter's BMI and AOM. Multiple regression analyses adjusted for covariates indicated a weak inverse association between maternal BMI and AOM and a much stronger inverse association between offspring BMI and AOM independent of maternal BMI.     

恐伤母研究子代肾虚的行为遗传

用猫吓孕鼠方法制造母代“恐伤肾”模型 ,然后对子代鼠的自由活动、攀登爬行、趋食、逃离电击区等8种遗传行为进行测试 ,结果发现 :先天肾虚子代鼠可有多种本能行为降低     

Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: A nested case–referent study

According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case–referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case‐index mother pair, three or four matched referent‐referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06–0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2–12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98–1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. © 2009 UICC     

Fatherhood status and prostate cancer risk

BACKGROUND: Whether fatherhood status affects prostate cancer risk remains controversial. Recently, it was proposed that childless men are at lower prostate cancer risk than men with children and that men with sons may be at lower risk than men with daughters only. METHODS: National population-based register data were used to address these associations between fatherhood status and prostate cancer risk. The cohort comprised all men born in Denmark between 1935 and 1988, among whom 3400 developed prostate cancer during a total of 51.6 million person-years of follow-up between 1968 and 2003. RESULTS: Childless men were found to be at a 16% reduced risk of prostate cancer compared with fathers (rate ratio [RR] of 0.84; 95% confidence interval [95% CI], 0.73-0.95). The sex of the offspring did not affect prostate cancer risk (fathers with sons vs fathers without sons: RR of 0.99; 95% CI, 0.90-1.08). Among fathers, a significant trend was observed of gradually reduced prostate cancer risk with increasing number of children (P = .009), a pattern applying to both sons (P = .01) and daughters (P = .04). CONCLUSIONS: Our national cohort study corroborates the view that men without children constitute a group that is at a moderately reduced risk of prostate cancer. Among men with children, there appears to be a linear decline in prostate cancer risk with increasing number of children that is independent of the sex of the offspring.     

氯胺酮对SD大鼠后代学习记忆功能影响的实验研究

目的研究孕期大鼠接受氯胺酮全身麻醉对其后代学习记忆功能的影响。方法将30只怀孕SD大鼠随机均分成氯胺酮组和对照组,每组15只。氯胺酮组怀孕SD大鼠经尾静脉持续输注氯胺酮麻醉2h,对照组则给予等体积的生理盐水。于出生后20d和30d用Morris水迷宫测试各大组所产子鼠的学习记忆功能,用透射电子显微镜观察两组子鼠海马组织超微结构。结果出生后20d和30d氯胺酮组子鼠逃避潜伏期较对照组长,出生后30d氯胺酮组子鼠第2次水迷宫试验所测得的逃避潜伏期明显较对照组长,差异有统计学意义（P〈0．05）,氯胺酮组子鼠海马组织神经元超微结构出现明显异常。结论母体孕期接受氯胺酮全身麻醉对SD大鼠后代学习记忆功能有损害作用,其机制与氯胺酮可引起后代海马区神经元损害有关。     

Maternal High-Fiber Diet Protects Offspring against Type 2 Diabetes

Previous studies have reported that maternal malnutrition is linked to increased risk of developing type 2 diabetes in adulthood. Although several diabetic risk factors associated with early-life environment have been identified, protective factors remain elusive. Here, we conducted a longitudinal study with 671 Nile rats whereby we examined the interplay between early-life environment (maternal diet) and later-life environment (offspring diet) using opposing diets that induce or prevent diet-induced diabetes. Specifically, we modulated the early-life environment throughout oogenesis, pregnancy, and nursing by feeding Nile rat dams a lifelong high-fiber diet to investigate whether the offspring are protected from type 2 diabetes. We found that exposure to a high-fiber maternal diet prior to weaning significantly lowered the risk of diet-induced diabetes in the offspring. Interestingly, offspring consuming a high-fiber diet after weaning did not develop diet-induced diabetes, even when exposed to a diabetogenic maternal diet. Here, we provide the first evidence that the protective effect of a high-fiber diet can be transmitted to the offspring through the maternal diet, which has important implications in diabetes prevention.