The gonadal expression pattern of lipocalin‑2 and 24p3 receptor is modified in the gonads of the offspring of obese rats

Abstract

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,

Overview of the expression patterns and roles of Lipocalin 2 in the reproductive system

“…In this study, the expression of the LCN2 receptor SLC22A17 was shown in germ cells at different developmental stages (42). On the contrary, a consecutive study done by the same group in 2020, reporting detectable LCN2 expression in Sertoli and Leydig cells (56). Although both publications contain manufacturer information on the antibody used (which was the same), only one of the studies provides information on the catalog number, therefore, it cannot be completely ruled out that different antibodies were used.…”

“…This scenario was as well observed in rat testicles of pups from obese mothers compared with control animals (56). However, the molecular mechanisms of Lcn2 regulation are poorly understood, but there is a general assumption that SLC22A17 and megalin play essential roles (56). Further studies should aim to understand the molecular mechanisms, which in turn will also allow conclusions to be drawn about the physiological function of LCN2.…”

“…Obesity affects not only LCN2 expression in adipocytes ( 58), but also in the reproductive tract. A study using rats showed that ovarian LCN2 strongly decreased in pups from obese mothers compared with pups of mothers fed control diet (56). This scenario was as well observed in rat testicles of pups from obese mothers compared with control animals (56).…”

“…A study using rats showed that ovarian LCN2 strongly decreased in pups from obese mothers compared with pups of mothers fed control diet (56). This scenario was as well observed in rat testicles of pups from obese mothers compared with control animals (56). However, the molecular mechanisms of Lcn2 regulation are poorly understood, but there is a general assumption that SLC22A17 and megalin play essential roles (56).…”