Parental ethanol consumption can influence the offspring phenotype. In this way, we analyzed the impairments of maternal and paternal high ethanol consumption during postpuberty on the physical development, feeding pattern, puberty onset and reproductive function of ethanol-naive offspring to birth to adulthood. Female and male UChB rats (voluntary 10%, v/v ethanol consumer) were divided into a control group (C) and an ethanol exposed group (E) from 65 to 80 days of age. The C and E were mated at 100 days. The maternal parameters and offspring development and reproduction parameters were monitored. We observed reduced feeding intake and body weight in the dams of E group throughout gestation and lactation period. Delay in physical development, lower body weight and altered feeding pattern were observed in female and male offspring of E group. In addition, the puberty onset was delayed in both sexes, with lower testosterone levels in the juvenile and pubertal males. There was a prolongation on the estrous and proestrus phases in females from E but the estrous cycle duration did not change between groups. Ovary and uterus weight were reduced in pubertal and adult females from E group. Reduced epididymis and seminal vesicle weight, increased sperm abnormalities, decrease in the daily sperm production and accelerated epididymal transit time were observed in E males. The high maternal and paternal ethanol use on postpuberty impairs the parameters of ethanol-naive offspring inducing alteration on development and reproduction.

Male infertility is responsible for 20-70% of infertility in couples. We investigated the effects of fetal programming with sodium saccharin consumption in testis structure and function and in male offspring fertility. Feed intake and efficiency, organ and fat weight, quantification and expression of AR and PCNA proteins, sperm count and hormonal dosages were performed. Changes in consumption were found in the final weeks of the experiment. Decreases in the expression and quantification of AR and PCNA, tubular diameter and luminal volume, and increase in epithelial and interstitial relative volumes were observed. Lower sperm count and transit and lower estradiol concentration were also found. The consumption of sodium saccharin by the dams programmed the male offspring affecting the HPG axis with alterations in Sertoli cell proliferation, AR expression and quantification, and sperm count. We hypothesize that these changes may be due to the reduction of estradiol that caused the loosening of the tight junctions of the blood-testis-barrier (BTB), causing cell losses during spermatogenesis, also reflecting, under the decrease in tubular diameter with an increase in epithelial volume and consequent decrease in luminal volume. Sodium saccharin programming directly affected the reproductive parameters of male offspring and adult fertility.

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We investigated the effects of fetal programming in rats Sprague–Dawley through the maternal consumption of sodium saccharin on the testicular structure and function in male offspring. Feed intake and efficiency, organ and fat weight, quantification and expression of AR and PCNA proteins, sperm count, and hormone levels were determined. Consumption alterations were found in the final weeks of the experiment. Decreases in AR and PCNA expression and quantification, tubular diameter and luminal volume, and increases in epithelial and interstitial relative volumes were observed. Lower sperm count and transit, and lower estradiol concentration were also found. Sodium saccharin consumption by dams programmed male offspring by affecting the HPG axis with alterations in the Sertoli cell population, in spermatogonia proliferation, the expression and quantification of AR, and in sperm count. We hypothesized that these changes may be due to an estradiol reduction that caused the loosening of adhesion junctions of the blood-testis barrier, causing cell losses during spermatogenesis, also reflected by a decrease in tubular diameter with an increase in epithelial volume and consequent decrease in luminal volume. We conclude that maternal sodium saccharin consumption during pregnancy and lactation programmed alterations in the reproductive parameters of male offspring, thus influencing spermatogenesis.

Resumo A Talidomida foi um medicamento amplamente comercializado na década de 1950, lançada ao mercado como um medicamento "completamente seguro e atóxico". Após sua descoberta como antiemético, foi indicado ao uso em gestantes e lactantes para tratamento de enjôos matinais. Na década de 1960, notou-se um aumento significativo no número de casos de nascimentos com malformação congênita de membros (chamada de Focomelia) sendo logo associada a droga devido a ingestão do medicamento nas semanas iniciais da gestação para o tratamento de enjôos matinais. Inúmeros casos de Embriopatia da Talidomida foram relatados, esta sendo uma condição que afeta vários órgãos e tecidos, porém a mais comum é a focomelia. Nosso estudo aponta quais são as alterações relacionadas a ingestão de talidomida nas semanas iniciais do desenvolvimento embrionário e alguns dos mecanismos descobertos que possam estar relacionados com essa patologia. Para isso foi realizada uma pesquisa descritiva de levantamento bibliográfico a partir de publicações científicas dos últimos dez anos. Concluímos portanto que a talidomida possui capacidade não só de causar danos nos membros mas também em órgãos internos e externos, além de outras que se evidenciam apenas na vida adulta, como o autismo. Para além, nosso estudo mostrou que o Brasil, mesmo após o medicamento ter sido banido a nível mundial, não regulamentou a fabricação e nem a distribuição deste, o que causou uma segunda geração de casos após 1960.

The relationship between adolescent ethanol uses and its impacts throughout life is not conclusive. Thus, we evaluated if the low and high consumption of ethanol during the postpuberty period interferes with reproduction in adulthood, the ethanol-naive offspring development and if there are dose-related effects. Females and males rats were divided into three groups: low drinker (L), with UChA rats fed with ethanol ad libitum drinking < 1.9 g / kg / day, high drinker (H), with UChB rats fed with ethanol ad libitum drinking from 2 to 5 g / kg / day, and control (C), with rats without access to ethanol. The L and H groups were exposed to ethanol 10% (v/ v) from 65 to 80 days, with withdrawal after this period. The study was conducted in two phases. The retrospective analysis (1st phase) verified the consumption of ethanol between sexes, the litter size, and the sex ratio of offspring. The gestational and reproductive parameters of parents and the development of pups were analyzed in the 2nd phase. We observed a higher consumption of ethanol in females and a reduced litter size in both drinkers groups. Body weight gain and gestational feed consumption were lower in L and H. The offspring body weight was also lower associated with alteration in landmarks of physical development. The high postpubertal ethanol use accents the impacts on consumers and offspring. The paternal and maternal reproductive organs weight was altered in group H, with an increase in morphologically abnormal sperm. We conclude that low and high post-pubertal alcohol consumption impairs reproductive parameters, even after withdrawal with long-term effects. Ethanol-naive offspring are also harmed, with effects associated with the dose of ethanol.

The relationship between adolescent ethanol uses and its impacts throughout life are not conclusive. Thus, we evaluated if the low and high consumption of ethanol at postpuberty interferes with the reproduction, ethanol-naive offspring and if the effects are dose-related. Female and male rats were divided into three groups: low drinker (L), high drinker (H), and control (C). The L and H groups were exposed to ethanol to 10% from 65 to 80 days with withdrawal after this period. The ethanol consumed by low drinkers was 1.41 ± 0.21 g/ kg / day and high drinkers 4.59 ± 0.45 g/ kg / day. The study was conducted in two phases. The 1st phase verified the reproductive capacity in adulthood on generations (litter size and sex ratio). Data were collected over ten years. The 2nd phase analyzed the parent reproductive parameters (body weight, reproductive organ weight, sperm parameters and estrous cycle) and the pup development. We observed a reduced litter size in both drinker groups. Gestational body weight gain and feed consumption were lower in L and H. We observed an alteration in reproductive organs weight in both sexes of H. Females presented a longer estrous cycle duration. Males presented an increase in abnormal sperm, a decrease in sperm count and accelerated transit time. The ethanol-naïve offspring development was also impaired. We conclude that low and high postpubertal alcohol use impairs long-term reproductive parameters, even after alcohol withdrawal. There is also impaired ethanol-naive offspring. Besides, the effects are dose-related.