Possible Role of Netrin-1/Deleted in Colorectal Cancer/Vascular Endothelial Growth Factor Signaling Pathway in the Pathogenesis of Placenta Accreta Spectrum: A Case-control Study.

SUMMARY: Netrin-1, an epithelial-secreted protein, plays a key role in placental formation through the promotion of cytotrophoblast proliferation and placental vascular development. These effects are mediated through several receptors, including the deleted in colorectal cancer (DCC) receptor. Placenta accreta spectrum (PAS) is an exaggerated trophoblastic invasion into the uterine myometrium. The exact etiology is unknown, but it is believed that increased trophoblastic invasion, defect decidualization, and/or abnormal angiogenesis might play a role. Our study aimed to investigate the suggested role of macrophage-induced netrin-1/DCC/vascular endothelial growth factor (VEGF) signaling in PAS pathogenesis. A total of 29 women with PAS (as cases) and 29 women with normal pregnancies (as controls) were enrolled in the study. At delivery, placental tissues of both groups were collected and processed for the evaluation of placental netrin-1 level by enzyme-linked immunoassay technique and immunohistochemical analysis of tissue DCC receptor. Placental tissue netrin-1 level of PAS cases showed a statistically significantly higher value than those in the normal group. Significant overexpression of DCC receptors, VEGF, and enhanced macrophage recruitment was noted in PAS cases in comparison to the normal placenta. Macrophage-induced netrin-1/DCC/VEGF signaling might be involved in PAS pathogenesis through the enhancement of trophoblastic angiogenesis.

Experimental obesity and diabetes reduce male fertility: Potential involvement of hypothalamic Kiss-1, pituitary nitric oxide, serum vaspin and visfatin.

Reproductive dysfunction is a common consequence of both obesity and diabetes. This study investigated the impact of obesity and diabetes, alone or combined, on physiological reproductive parameters in male rats. Twenty-four male Wistar Albino rats were divided into four groups: Control; obese non-diabetic; diabetic; and obese diabetic. Obesity was provoked by consumption of a high-fat diet (HFD) consisting of 40% energy from fat for 90 days. Diabetes was induced by an intraperitoneal injection of streptozotocin at a dose of 40 mg/kg/day for three consecutive days. Semen, histopathological, and morphometric analyses were carried out. Serum testosterone, luteinizing hormone (LH), and vaspin and visfatin were measured using ELISA kits. Hypothalamic Kiss-1 mRNA was detected using qPCR and pituitary nitric oxide (NO) was determined using Griess reagent. Our results showed a decrease in semen quality parameters, testosterone, and LH levels with degenerative changes in the testes in experimental groups when compared to control group. This had a positive correlation with hypothalamic Kiss-1 and a negative correlation with pituitary NO and serum vaspin and visfatin. In addition, adverse effects were more pronounced in animals with obesity and diabetes combined compared to rats who were either diabetic or obese. In conclusion, obesity and diabetes, alone or combined, had a negative impact on male rat fertility. Moreover, obesity and diabetes combined had more harmful effects on male fertility when compared with obesity alone. Hypothalamic Kiss-1, pituitary NO, and serum vaspin and visfatin may play a role in the pathophysiology of male infertility-associated with obesity and diabetes.