Thyroid Hormones and Functional Ovarian Reserve: Systemic vs. Peripheral Dysfunctions.

Thyroid hormones (THs) exert pleiotropic effects in different mammalian organs, including gonads. Genetic and non-genetic factors, such as ageing and environmental stressors (e.g., low-iodine intake, exposure to endocrine disruptors, etc.), can alter T4/T3 synthesis by the thyroid. In any case, peripheral T3, controlled by tissue-specific enzymes (deiodinases), receptors and transporters, ensures organ homeostasis. Conflicting reports suggest that both hypothyroidism and hyperthyroidism, assessed by mean of circulating T4, T3 and Thyroid-Stimulating Hormone (TSH), could affect the functionality of the ovarian reserve determining infertility. The relationship between ovarian T3 level and functional ovarian reserve (FOR) is poorly understood despite that the modifications of local T3 metabolism and signalling have been associated with dysfunctions of several organs. Here, we will summarize the current knowledge on the role of TH signalling and its crosstalk with other pathways in controlling the physiological and premature ovarian ageing and, finally, in preserving FOR. We will consider separately the reports describing the effects of circulating and local THs on the ovarian health to elucidate their role in ovarian dysfunctions.