No abstract

Perturbations in the levels of serotonin expression have a significant impact on behavior and have been implicated in the pathogenesis of several neuropsychiatric disorders including anxiety, mood and appetite. Fetal programming is a risk factor for the development of metabolic diseases during adulthood. Moreover, previous studies have shown that serotonin (5-HT), dopamine and leptin are important in energy balance. In the present study, the impact of maternal malnutrition-induced prenatal undernutrition (UN) was investigated in mice and the expression of 5-HT1A, dopamine (D)1, D2 and Ob-Rb receptors was analyzed in the hypothalamus during adulthood. The UN group showed a low birth weight compared with the control group. With regard to receptor expression, 5-HT1A in the UN group was increased in the hypothalamus and D1 was reduced, whereas D2 showed an increase from postnatal day (P)14 in the arcuate nucleus. Ob-Rb receptor expression was increased in the hypothalamus at P14 and P90. These observations indicated that maternal caloric restriction programs a postnatal body weight gain in offspring with an increased food intake in early postnatal life which continues into adulthood. In addition, UN in mice was found to be affected by Ob-Rb, 5-HT1A and D1/2 receptor expression, indicating that these observations may be associated with hyperphagia and obesity.

Numerous clinical studies have reported the association between high circulating levels of lipocalin-2 (LCN2) and metabolic diseases. However, only few studies have addressed sexually dimorphic, either in its circulating concentration or in its expression in other organs. To the best of our knowledge, LCN2 and the 24p3 receptor (24p3R), have not been identified in gonads; therefore, the present study analyzed their mRNA expression profile and cellular localization in gonads collected from fetal rats at 21 days post coitum, as well as from neonatal rats at 0, 2, 4, 6, 12, 20 and 30 postnatal days. Semiquantitative polymerase chain reaction and immunohistochemical assays revealed that the LCN2 mRNA during perinatal and pre-pubertal stages presented a sex-specific expression pattern, being higher in ovaries than in testes collected at these stages. Furthermore, the mRNA levels of the long and short isoforms of the 24p3R (507 and 350 bp, respectively), were lower in female gonads from postnatal day 0 onwards in comparison with the levels observed in males, but before birth, the short isoform of the 24p3R was higher in ovaries than in testes. In addition, in females, the abundance of mRNA of this isoform was drastically diminished at 24 h after birth. Furthermore, this specific expression profile of LCN2 and 24p3R at perinatal and prepubertal stages coincides with events of cellular proliferation and apoptosis within both gonads. Immunohistochemical assays revealed that in ovaries, LCN2 and 24p3R are present in germinal and somatic cells of follicles, while in testes, this adipokine and its receptor are only located in germinal cells. These findings suggest that in murine gonads, LCN2/24p3R signaling may be involved either in cell proliferation or cell death driven by gonadotropin-independent or -dependent mechanisms.

obesity represents a global health and economic burden, affecting millions of individuals worldwide. This pathology is associated with a chronic low-grade inflammatory state that is partially responsible for the development of other cardiometabolic complications. clinical studies have reported an association between high circulating levels of lipocalin-2 (lcn2) and increased body weight. additionally, there is scientific evidence demonstrating the impact of maternal obesity on fetal programming. The latter and the fact that the authors previously found that lcn2 and its receptor (24p3r) are expressed in the gonads of wild-type rats, led to the analysis of their mRNA profile and cellular localization in gonads collected from the offspring of obese rats at 21 days postconception (dpc), and 0, 2, 4, 6, 12, 20 and 30 days postnatal (dpn) in the present study. Semi-quantitative Pcr revealed a statistically significant downregulation of Lcn2 and 24p3R mrna at 21 dpc in the ovaries (P<0.01) and testicles (P<0.001) of the offspring of obese mothers. at 30 dpn, the relative expression of Lcn2 mRNA decreased significantly in the ovaries of the experimental group (P<0.05), while Lcn2 mrna expression was not detectable in testicles. regarding 24p3R, its mRNA was only significantly decreased at 21 dpc in ovaries of pups of obese mothers. at 30 dpn, the change in females was not significant. conversely, in testicles, 24p3R mrna levels increased slightly in the experimental group at 30 dpn. The lcn2 protein signal was less intense in gonadal tissue sections from 30 dpn offspring of obese rats (P<0.001), whereas the 24p3r signal was downregulated in ovaries (P<0.001) and slightly upregulated in testicles. it was concluded that maternal obesity changes the expression of lcn2 and 24p3r in the gonads of the offspring of obese rats, possibly through fetal programming. The consequences of this dysregulation for the offspring's gonadal function remains to be determined. 1 cardiovascular and Metabolic diseases research unit; 2 endocrine research unit, national Medical center,