The ‘beneficial’ adipokines in reproduction and fertility

Abstract

The objective of this study was to review the available information on the signaling proteins produced by adipose tissue in the context of their role in regulating reproductive processes, including ovarian and uterine function. It is well known that both obesity and excessive leanness are associated with reproductive dysfunction. Adipokines are cytokines predominately or exclusively expressed by adipose tissue that circulate and affect target tissues. Four known adipokines, adiponectin, visfatin/ PBEF, omentin and vaspin, all increase tissue sensitivity to insulin, and are thus described as 'beneficial'. There is strong support for a role for adiponectin in the function of the ovary and placenta. There is evidence for direct effects of this adipokine on the late stages of folliculogenesis, and additive interactions of adiponectin with insulin and gonadotropins in inducing periovulatory changes in ovarian follicles. In addition, clinical and genomic studies associate hypoadiponectinemia with obesity-related reproductive disorders, including the polycystic ovarian syndrome. The roles for visfatin/PBEF, omentin and vaspin in reproduction remain to be established. The conclusion thus drawn is that the expression of insulin-sensitizing adipokines varies with adipose abundance. These adipokines have demonstrated both the potential effects on ovarian function and the possible effects on the formation of the placenta, acting through multiple mechanisms.

Effects of adiponectin on human trophoblast invasion

“…In addition to its role in energy homeostasis, adiponectin exerts a protective action against gastric, prostate, and breast cancer development (Mantzoros et al 2004, Bub et al 2006, Ishikawa et al 2007. Some evidence suggests that adiponectin could also directly regulate reproductive and placental processes (Mitchell et al 2005, Campos et al 2008 as already described for another adipocytokine leptin (Chehab 2000). Furthermore, it was demonstrated that, in human endometrium, adiponectin receptor levels are the highest during the luteal period, which corresponds to the embryo implantation period (Takemura et al 2006a).…”

Adipokines in reproductive function: a link between obesity and polycystic ovary syndrome

“…APN is described as a 'beneficial' adipokine in reproduction (Campos et al 2007). Both ADIPOR1 and ADIPOR2 are expressed in human hypothalamus and pituitary (Rodriguez-Pacheco et al 2006, Kubota et al 2007.…”

“…APN, also referred to as ACRP30 or AdipoQ, is the most abundant secreted protein expressed exclusively in adipose tissue (Campos et al 2007, Bohler et al 2010). There are three major forms of APN: a trimeric low-molecular-weight (LMW) form, a hexameric medium-molecular-weight (MMW) form, and a multimeric high-molecular-weight (HMW) form (Kadowaki & Yamauchi 2005, Michalakis & Segars 2010.…”

Adiponectin limits differentiation and trophoblast invasion in human endometrial cells

“…Adiponectin exerts its action via two specific receptors (ADIPOR1 and ADIPOR2) containing seven transmembrane domains but which are structurally and functionally distinct from G-protein-coupled receptors (Yamauchi et al 2003a). By binding to ADIPORs, adiponectin activates a variety of targets, such as protein kinase A, phosphoinositide-3 kinase, mitogen-activated protein kinase and most notably, the AMP-activated protein kinase through which adiponectin exerts its insulin-sensitizing effects (Yamauchi et al 2003a, Campos et al 2008. This adipokine has also been shown to exert anti-inflammatory, anti-angiogenic, antiatherosclerotic, anti-proliferative and pro-apoptotic roles in various cell types (Yamauchi et al 2003b, Dieudonne et al 2006, Duval et al 2016.…”