Obesity as disruptor of the female fertility

Erica Silvestris, Giovanni de Pergola, Raffaele Rosania, Giuseppe Loverro, Erica Silvestris, Giovanni de Pergola, Raffaele Rosania, Giuseppe Loverro

Abstract

Both obesity and overweight are increasing worldwide and have detrimental influences on several human body functions including the reproductive health. In particular, obese women undergo perturbations of the 'hypothalamic pituitary ovarian axis', and frequently suffer of menstrual dysfunction leading to anovulation and infertility. Besides the hormone disorders and subfertility that are common in the polycystic ovary syndrome (PCOS), in obesity the adipocytes act as endocrine organ. The adipose tissue indeed, releases a number of bioactive molecules, namely adipokines, that variably interact with multiple molecular pathways of insulin resistance, inflammation, hypertension, cardiovascular risk, coagulation, and oocyte differentiation and maturation. Moreover, endometrial implantation and other reproductive functions are affected in obese women with complications including delayed conceptions, increased miscarriage rate, reduced outcomes in assisted conception treatments.On the contrary, weight loss programs through lifestyle modification in obese women, have been proven to restore menstrual cyclicity and ovulation and improve the likelihood of conception.

Keywords: Adipokines; Anovulation; Infertility; Obesity; Oocytes.

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Figures

Fig. 1
Fig. 1
Functional properties of adipocites
Fig. 2
Fig. 2
Pathophysioly of insuline resistance. This figure illustrates the complex interactions underlying the pathophysiology of PCOS. Insulin resistance and the resulting hyperinsulinemia are responsible for the majority of the changes found in PCOS. Insulin resistance in PCOS does not occur in all tissues, but rather appears to be tissue-specific. Skeletal-muscle and adipose tissue become insulin resistance resulting in decrease glucose uptake and increased lipolysis, respectively, whereas the ovary, adrenal and liver remain insulin sensitive. In PCOS, hyperinsulinemia occurs as a compensatory response to insulin resistance. This resulting hyperinsulinemia has a stimulatory effect on the ovaries and adrenal glands that leads to enhanced androgen production by these organs. More specifically, excess insulin enhances androgen production in ovarian theca cells in response to luteinizing hormone (LH) stimulation, resulting in follicular arrest and anovulation. In contrast hyperinsulinemia acts to suppress hepatic production of sex hormone-binding globulin (SHBG), the primary binding protein for testosterone in the serum. Therefore, insuline resistance whith compensatory hyperinsulinemia results in hyperandrogenemia
Fig. 3
Fig. 3
Insulin receptor tyrosine kinases. The α subunit binds insulin and the β transmits a signal from bound insulin to the cytoplasm. The insulin signal activates the receptor’s protein kinases domain in the cytoplasm. Proteine kinases from the receptor phosphorylate insuline-response substrates triggering other chemical responses inside the cell. When IGFBPs binds and therefore activates the IGF-Ir, the hepatic synthesis of IGFBP-I is decreased, making IGF-I more biologically available, thus enhancing androgen production by theca interstitial and stromal cells

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