Maternal hyperglycemia affects cell proliferation signalling and stromal organization in the prostate of neonatal and juvenile rat offspring.

Gestational diabetes mellitus is a common medical complication during pregnancy. It creates a hyperglycemic environment and impacts offspring development, increasing the risk of long-term complications, including obesity, impaired glucose metabolism and cardiovascular disease. The impact of gestational diabetes on the prostates of adult offspring has already been described; however, it is not known whether these effects are due only to the maternal condition or whether the offspring develop them throughout life. This investigation evaluated the prostates of neonatal and juvenile offspring of hyperglycemic rats due to diabetes. Diabetes was induced with streptozotocin (50 mg/kg, ip) in pregnant Wistar rats and the prostates of 7- or 30-day-old pups from healthy (PC7, PC30) or diabetic (PD7, PD30) mothers were evaluated. We found reduced body weight in pups of PD7 and PD30 and prostate weight in PD30. Prostate branching was not affected, but a reduction in apoptotic levels was associated with impaired acinar bud canalization in neonates. Additionally, PD7 presented reduced ERK1/2 phosphorylation, cell proliferation and collagen, but fibroblasts were increased. In PD30, there was a reduction in the area of the secretory epithelium and stroma, but the luminal area was increased. Moreover, fibroblasts, smooth muscle cells, collagen and metalloproteinase 2 were decreased in these juvenile pups. These data indicate that maternal hyperglycemia inactivates an important cell proliferation signaling pathway in the prostate in the first postnatal days (which is restored in the juvenile period), but it was not sufficient to avoid epithelial and stromal atrophy. This effect on postnatal gland development may impact the reproductive capacity of the prostate in adult life.

Peixoto LFF ，Sudário LED ，Silva MDGCE ，Mascarenhas FNADP ，Muniz EH ，Zanon RG ，Ribeiro DL ... -  《-》

Streptozotocin-Induced Maternal Hyperglycemia Increases the Expression of Antioxidant Enzymes and Mast Cell Number in Offspring Rat Ventral Prostate.

Gestational diabetes mellitus (GDM) has increased in recent years. Although the cellular and molecular mechanisms involved in GDM-increased risk factors to offspring remained poorly understood, some studies suggested an association between an increase in oxidative stress induced by maternal hyperglycemia and complications for both mothers and newborns. Here, we investigated the impact of maternal hyperglycemia followed by maternal insulin replacement during lactation on the expression of antioxidant enzymes and mast cell number in offspring ventral prostate (VP) at puberty. Pregnant rats were divided into three groups: control (CT); streptozotocin-induced maternal hyperglycemia (MH); and MH plus maternal insulin replacement during lactation (MHI). Male offspring were euthanized at postnatal day (PND) 60 and the VP was removed and processed for histology and Western blotting analyses. Maternal hyperglycemia delayed prostate maturation, and increased mast cell number catalase (CAT), superoxide dismutase (SOD), glutatione-s-transferase (GST-pi), and cyclooxygenase-2 (Cox-2) expression in the offspring of hyperglycemic dams. Maternal insulin replacement restored VP structure, mast cell number and antioxidant protein expression, except for Cox-2, which remained higher in the MHI group. Thus, an increase in oxidative stress induced by intrauterine hyperglycemia impacts prostate development and maturation, which persists until puberty. The overall improvement of maternal metabolism after insulin administration contributes to the restoration of prostate antioxidant enzymes and secretory function. Taken together, our results highlighted that imbalanced physiological maternal-fetal interaction contributes to the impairment of reproductive performance of the offspring from diabetic mothers. Anat Rec, 300:291-299, 2017. © 2016 Wiley Periodicals, Inc.

Camargo AC ，Dos Santos SA ，Rinaldi JC ，Constantino FB ，Colombelli KT ，Scarano WR ，Felisbino SL ，Justulin LA ... -  《-》

Effects of maternal diabetes on male offspring: high cell proliferation and increased activity of MMP-2 in the ventral prostate.

Damasceno AA ，Carvalho CP ，Santos EM ，Botelho FV ，Araújo FA ，Deconte SR ，Tomiosso TC ，Balbi AP ，Zanon RG ，Taboga SR ，Góes RM ，Ribeiro DL ... -  《-》

[Effects of severe hyperglycaemia in pregnancy and early overfeeding on islet development and insulin resistance].

Zeng CJ ，Zhang L ，Yang HX 《-》

Impact of gestational diabetes and lactational insulin replacement on structure and secretory function of offspring rat ventral prostate.

Clinical and experimental studies have shown that exposure to adverse conditions during the critical stages of embryonic, fetal or neonatal development lead to a significantly increased risk of later disease. Diabetes during pregnancy has been linked to increased risk of obesity and diabetes in offspring. Here, we investigated whether mild gestational diabetes mellitus (GDM) followed or not by maternal insulin replacement affects the ventral prostate (VP) structure and function in male offspring at puberty and adulthood. Pregnant rats were divided into the following 3 groups: control (CT); streptozotocin (STZ)-induced diabetes (D); and D plus insulin replacement during lactation (GDI). The male offspring from different groups were euthanized at postnatal day (PND) 60 and 120. Biometrical parameters, hormonal levels and prostates were evaluated. Mild-GDM promoted reduction in the glandular parenchyma and increased collagen deposition. Insulin replacement during lactation restored the VP morphology. Most importantly, mild-GDM decreased the androgen-induced secretory function as determined by prostatein expression, and insulin replacement reversed this effect. Our results demonstrated that mild GDM impairs VP parenchyma maturation, which is associated with an increase in the fibromuscular stroma compartment. Functionally, the reduction in the VP parenchyma decreases the glandular secretory activity as demonstrated by low expression of prostatein, a potent immunosuppressor factor that protects sperm from immunologic damage into the feminine reproductive tract. This change could lead to impairment of reproductive function in male offspring from diabetic mothers. Maternal insulin replacement during the weaning period apparently restores the prostate function in male offspring.

Santos SA ，Rinaldi JC ，Martins AE ，Camargo AC ，Leonelli C ，Delella FK ，Felisbino SL ，Justulin LA Jr ... -  《-》