A proteomic study of the effects of nutrient restriction in utero on postnatal metabolism

It is widely recognized that protein restriction in utero may cause metabolic and endocrine adaptations, which may be of benefit to the neonate on a short-term basis but may cause adverse long-term conditions such as obesity, Type 2 diabetes, metabolic syndrome, hypertension and cardiovascular diseases. Adequate foetal and early post natal nutrient and energy supply is therefore essential for adult animal health, performance and life span. In this project it was investigated the progressive adaptations of the hepatic proteome in male mink offspring exposed to either a low protein (FL) or an adequate protein (FA) diet in utero fed either on a low protein (LP) or on an adequate (AP) diet from weaning until sexual maturity. Specifically, the aim was to determine the metabolic adaptations at selected phases of the animal’s first annual cycle and establish the metabolic priorities occurring during those phases. The three different morphological stages studied during the first year of development included, end of bone growth at 4 months of age, maximal fat accretion at 6 months of age and sexual maturity at 12 months of age. A reference proteome of mink liver coming from these different animal groups were generated using 2D electrophoresis coupled to MALDI-TOF analysis and the way in which dietary treatment affect their proteome was established. Approximately 330 proteins were detected in the mink liver proteome. A total of 27 comparisons were carried out between all different animal groups which resulted in 20 differentially expressed proteins. An extensive survey was conducted towards the characterization of these proteins including their subcellular localization, the biological processes in which they are involved and their molecular functions. This characterization allowed the identification of proteins in various processes including the glycolysis and fatty acid metabolism. The detailed analysis of the different dietary treatment animal groups was indicative of differences in metabolism and also to changes associated with development in mink.

Evidence for interplay between genes and maternal stress in utero: monoamine oxidase A polymorphism moderates effects of life events during pregnancy on infant negative emotionality at 5 weeks

The low activity variant of the monoamine oxidase A (MAOA) functional promoter polymorphism, MAOA-LPR, in interaction with adverse environments (G × E) is associated with child and adult antisocial behaviour disorders. MAOA is expressed during foetal development so in utero G × E may influence early neurodevelopment. We tested the hypothesis that MAOA G × E during pregnancy predicts infant negative emotionality soon after birth. In an epidemiological longitudinal study starting in pregnancy, using a two stage stratified design, we ascertained MAOA-LPR status (low vs. high activity variants) from the saliva of 209 infants (104 boys and 105 girls), and examined predictions to observed infant negative emotionality at 5 weeks post-partum from life events during pregnancy. In analyses weighted to provide estimates for the general population, and including possible confounders for life events, there was an MAOA status by life events interaction (P = 0.017). There was also an interaction between MAOA status and neighbourhood deprivation (P = 0.028). Both interactions arose from a greater effect of increasing life events on negative emotionality in the MAOA-LPR low activity, compared with MAOA-LPR high activity infants. The study provides the first evidence of moderation by MAOA-LPR of the effect of the social environment in pregnancy on negative emotionality in infancy, an early risk for the development of child and adult antisocial behaviour disorders.

In utero and lactational exposure to fenvalerate disrupts reproductive function in female rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Reproductive development and function of female rats exposed to di-eta-butyl-phthalate (DBP) in utero and during lactation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

SPERM QUALITY IN ADULT MALE RATS EXPOSED TO CADMIUM IN UTERO and LACTATION

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Functional and Morphological Reproductive Aspects in Male Rats Exposed to Di-n-Butyl Phthalate (DBP) in Utero and During Lactation

The potential adverse reproductive effects, with emphasis on the epididymis, of in utero and lactational exposure to 100 mg/kg/d di-n-butyl phthalate (DBP) in adult male rat offspring were investigated. The fetal testis histopathology was also determined. The selected endpoints included reproductive organ weights, sperm motility and morphology, sperm epididymal transit time, sperm quantity in the testis and epididymis, hormonal status, fetal testis and epididymal histopathology and stereology, and androgen receptor (AR), aquaporin 9 (AQP9), and Ki-67 immunoreactivities. Pregnant females were divided into two groups: control (C) and treated (T). The treated females received DBP (100 mg/kg/d, by gavage) from gestation day (GD) 12 to postnatal day (PND) 21, while control dams received the vehicle. Some pregnant dams were killed by decapitation on GD20, and testes from male fetuses were collected for histopathogy. Male rats from other dams were killed at PND 90. Fetal testes from treated group showed Leydig-cell clusters, presence of multinucleated germinative cells, and increase of the interstitial component. Testosterone levels and reproductive organ weights were similar between the treated and control adult groups. DBP treatment did not markedly affect relative proportions of epithelial, stromal, or luminal compartments in the epididymis; sperm counts in the testis and epididymis; sperm transit time; or sperm morphology and motility in adult rats. The AR and AQP9 immunoreactivities and proliferation index were similar for the two groups. These results showed that fetal testes were affected by DBP as evidenced by testicular histopathologic alterations, but reproductive parameters and epididymal structure/function were not significantly altered in the adult animals exposed to 100 mg/kg DBP in utero and during lactation.

In utero protein restriction causes growth delay and alters sperm parameters in adult male rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exposição in utero ao desregulador endocrino bisfenol A e ao agente quimiopreventivo indol-3-carbinol: efeitos sobra a morfogênese e a suscetibilidade à carcinogênese prostática

Pós-graduação em Biologia Geral e Aplicada - IBB

Programaçao fetal por restrição proteica in utero: avaliação do imprinting estrogênico nas próstatas ventral e dorsolateral do rato Wistar

Pós-graduação em Biologia Geral e Aplicada - IBB

Exposição in utero ao desregulador endócrino Bisfenol A e à Genisteína: efeitos sobre a morfogênese e a susceptibilidade a carcinogênese prostática em ratos Sprague-Dawley

Pós-graduação em Patologia - FMB

Avaliação da exposição ao propionato de testosterona em ratas fêmeas in utero e lactação

It is known that exposure to substances in the environment can contribute to various reproductive disorders, especially if such exposure occurs during critical periods of development such as the intra-uterine and postnatal. The female reproductive system may be the target of androgens, both as a result of exposure to environmental chemicals, or by pathological conditions (polycystic ovary syndrome or congenital adrenal hyperplasia).Usually, little attention is given off in relation to the study of androgenic effects in the female reproductive axis. This study aims to evaluate the effects of exposure to androgens on the development, structure and reproductive function in rats whose mothers were exposed to testosterone propionate from gestational day 12 (DG12) after weaning - postnatal day 21 (DPN21) . For this purpose, pregnancy rats were divided into four groups: a control group that received corn oil (vehicle) and three groups receiving testosterone propionate in doses of 0.05 mg / kg / day, 0.1 mg / kg / day and 0.2 mg / kg / day, all under the same experimental conditions. The possible effects of exposure were assessed using reproductive parameters, such as a measure of anogenital distance, count areolas / nipples, age at vaginal opening and first estrus (puberty indicative installation), weight and histological evaluation of the reproductive organs ( uterus and ovaries), weight of the kidneys, liver and pituitary hormone levels, regularity of the estrous cycle, sexual behavior and fertility. Such analysis is important in understanding the effects of androgen exposure on the female genital system, especially on the reproductive potential, and processes that may involve morphofunctional changes. In these experimental conditions, it is concluded that treatment with PT caused reduction in body weight and initial masculinization in females without cubs, however, commit further sexual development

Genistein reduces the noxious effects of in utero bisphenol A exposure on the rat prostate gland at weaning and in adulthood

Bisphenol A (BPA) is one hormonally active chemical with potential deleterious effects on reproductive organs, including breast and prostate. In contrast, genistein (GEN) is the major phytoestrogen of soy that presents potential protective effects against hormone-dependent cancers, including that of the prostate. Thus, pregnant Sprague-Dawley rats were treated with BPA at 25 or 250 μg/kg/day by gavage from gestational day (GD) 10-21 with or without dietary GEN at 250 mg/kg/chow (∼5.5 mg/kg/day). Then, male offspring from different litters were euthanized on post-natal day (PND) 21 and 180. At PND21, BPA 25 exposure induced early prostatic changes while dietary GEN attenuated some deleterious actions this xenoestrogen on epithelial cell proliferation levels, androgen receptor expression and prostatic architecture in male offspring. At PND180, a significant increase in incidence of prostatic multifocal inflammation/reactive hyperplasia and atypical hyperplasia were observed in male offspring from dams that received BPA 25. On the other hand, maternal GEN feeding attenuated some the adverse effects of BPA 25 on prostate disease at late-in-life. This way, the present findings point to preventive action of dietary GEN on deleterious effects of gestational BPA exposure in both early and late prostate development in offspring F1.

Criptorquidia e exposição in utero ao di(n-butil)-ftalato e à acrilamida: avaliação morfológica do dano testicular

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)