0000000000182433
AUTHOR
Ana Cervero
The role of the leptin in reproduction.
Since its discovery in 1994, leptin has appeared to be a pleiotrophic hormone, governing energy homeostasis and affecting many tissues in the body. Numerous pieces of evidence have accumulated showing that leptin potentially plays an important role in the control of the reproductive function.This review presents the major concepts for the role of leptin in the modulation of reproductive function. As a marker of the nutritional status, leptin affects the hypothalamo-pituitary-gonadal axis, regulating gonadotrophin-releasing hormone and luteinising hormone secretion, and appears to be a permissive factor in the onset of the puberty. This protein and its receptor have been found in the reprodu…
Human endometrial CD98 is essential for blastocyst adhesion.
Background Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans. Methods and Principal Findings Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surfac…
The leptin system during human endometrial receptivity and preimplantation development.
The leptin system is implicated in the regulation of body weight and reproductive function, acting at endocrine and paracrine levels. This ligand-receptor system is mandatory for embryonic implantation in rodents. Here, we investigate the expression pattern of total leptin receptor (OB-R(T)), the long form (OB-R(L)) and short isoforms HuB219.1 and HuB219.3 in the human endometrium. Furthermore, we studied leptin and OB-R(T) mRNA during human embryonic preimplantation development and the embryonic regulation of the endometrial OB-R(L). Leptin receptor expression and its isoforms increase in the luteal phase and peak in the late part. Leptin receptor was localized at the epithelial and glandu…
A combined approach for gene discovery identifies insulin-like growth factor-binding protein-related protein 1 as a new gene implicated in human endometrial receptivity.
In the past, human endometrial receptivity has been investigated by chasing specific molecules throughout the menstrual cycle. Now the genomic approach allows us to investigate the hierarchical contribution of a high number of genes to a specific function. In this study, we analyzed differentially the gene expression pattern of 375 human cytokines, chemokines, and related factors, plus that of their receptors, in endometrial receptivity. To do this, we used a combined approach of human endometrium and cell lines. We have compared the gene expression pattern in receptive vs. prereceptive human endometria and contrasted the results with gene expression in the highly adhesive cell line (to JAR…
Embryonic adhesion is not affected by endometrial leptin receptor gene silencing.
Objective In rodents, evidence suggests that the leptin system is mandatory for embryonic implantation. We aimed to investigate the functional relevance of the endometrial leptin receptor (OB-R) in the adhesion phase of human implantation. Design We used an in vitro model for embryonic adhesion, composed of a human endometrial cell line (HEC1-A) and B6C3F1 mouse embryos. The OB-R gene was silenced in a stable manner by RNA interference, and embryonic adhesion rates were analyzed. Setting Research laboratory at a university-affiliated center. Intervention(s) RNA interference. Main Outcome Measure(s) Embryonic adhesion in cells treated with OB-R RNAi. Result(s) The OB-R shRNA-transfected cell…
Proprotein convertase 5/6 is critical for embryo implantation in women: regulating receptivity by cleaving ebp50, modulating ezrin binding, and membrane-cytoskeletal interactions
Establishment of endometrial receptivity is vital for successful embryo implantation; its failure causes infertility. Epithelial receptivity acquisition involves dramatic structural changes in the plasma membrane and cytoskeleton. Proprotein convertase 5/6 (PC6), a serine protease of the proprotein convertase (PC) family, is up-regulated in the human endometrium specifically at the time of epithelial receptivity and stromal cell decidualization. PC6 is the only PC member tightly regulated in this manner. The current study addressed the importance and mechanisms of PC6 action in regulating receptivity in women. PC6 was dysregulated in the endometrial epithelium during the window of implantat…
Determinants of endometrial receptivity.
Understanding the molecular changes that occur during the window of implantation is fundamental to our knowledge of human reproduction. Lately, the development of microarray technology has allowed this process to be studied from a global molecular perspective. In the last 2 years, researchers have focused their efforts on throwing light on the gene expression profile of the receptive endometrium. The genes hold the key to the development of the endometrium at any stage, and we have focused our work on the window of implantation. The four most recently published works in this field have revealed a long list of genes that are up- or downregulated at the time of implantation. Although these st…
Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system.
Objective To summarize the effects of novel hormones (leptin, ghrelin, adiponectin, resistin, and PYY3-36) secreted from adipose tissue and the gastrointestinal tract that have been discovered to exert different effects on several reproductive functions, such as the hypothalamic–pituitary–gonadal axis, embryo development, implantation physiology, and clinically relevant conditions. Design A MEDLINE computer search was performed to identify relevant articles. Result(s) Leptin and ghrelin exert important roles on body weight regulation, eating behavior, and reproduction, acting on the central nervous system and target reproductive organs. As a marker of adequate nutritional stores, these horm…