Leptin and reproduction

Abstract

Leptin, the product of the ob gene, is a small peptide molecule synthesized by white adipocytes with an important role in the regulation of body fat and food intake. Leptin and leptin receptor mRNA were first detected in the brain and hypothalamus but now their ubiquitous presence has been demonstrated. Leptin receptor signal transduction involves the activation of signal transducer and activator of transcription (STAT)-3, a member of the transcription family of proteins. Leptin is regulated by hormones and cytokines, interleukin-1, tumour necrosis factor-alpha and transforming growth factor-beta, linking this molecule with the inflammatory response. In addition, emerging evidence has demonstrated that this molecule is related to reproductive function. This small protein is present in the ovary and decidua, in mature oocytes and during embryonic development and trophoblast invasion. Animal models have demonstrated that leptin-deficient ob/ob mice are sterile; however, fertility can be restored by exogenous leptin. In addition, embryos implanted in STAT-3-deficient mice degenerate rapidly and are the target disruption of STAT-3-provoked embryonic lethality. Leptin acts as a novel placental hormone participating in the control of fetal growth and development. Leptin could be a modulator for invasive features of cytotrophoblast cells. We postulate that leptin may have an autocrine/paracrine role in human implantation and placentation.

The utility of serum leptin and follicular fluid leptin, estradiol, and progesterone levels during an in vitro fertilization cycle

“…Another study has shown a possible relationship with the implantation process by demonstrating an increase in leptin receptor levels in healthy non-pregnant women during the menstrual cycle reaching a peak near ovulation, then declining at menstruation [5].…”

Gene expression and protein distribution of leptin and its receptor in bovine oocytes and preattachment embryos produced in vitro

“…Furthermore, these molecules were identified in balloon-like structures connected to the apical surface of granulosa cells . Leptin is localised in human and mouse ovaries (Gonzalez et al, 2000) and in human follicular fluid (Welt et al, 2003) pointing the potential source of exogenous leptin and the site of entry. Studies show that mitochondria regularly migrate during oocyte maturation.…”

“…Moreover, the presence of leptin receptor in mouse, bat (Zhao et al, 2004), rat (Smith and Waddell, 2002) and human (Castellucci et al, 2000) placenta seems to support the idea of leptin's importance at the later stages of trophoblast invasion as well as during foetal development. In addition to its expression in the developing embryo, leptin has also been detected in mouse uterine fluid (Kawamura et al, 2003) and found to be secreted by human endometrium (Gonzalez et al, 2000). In vitro studies on mice showed that leptin stimulates the secretion of b3-integrin and promotes cell adhesion to the extracellular matrix proteins (Yang et al, 2006).…”

“…On the other hand, an elevated concentration of leptin in the serum (59.48 ng/ml) appeared to reduce ovarian stimulation, response and follicle maturation in humans with associated poor embryo quality and pregnancy failure (Anifandis et al, 2005), indicating that there is a need to maintain a certain physiological level of leptin. Moreover, biochemical analyses reveal a higher level of leptin in the culture medium of competent human blastocysts as compared to that of low-quality embryos (Gonzalez et al, 2000). The actions of leptin may involve both the paracrine and autocrine pathways.…”

“…The actions of leptin may involve both the paracrine and autocrine pathways. The protein has been identified in mouse oviduct fluid (Kawamura et al, 2003), pig oviduct epithelium (Craig et al, 2005) and human endometrium (Gonzalez et al, 2000) as well as human and mouse oocytes and preimplantation embryos . The spatial distribution of leptin protein in mouse and human oocytes and preimplantation embryos is polarised within the oocyte and after fertilisation .…”