Quantitative proteomic profile analysis of thyroid dysfunction effects on seminal vesicles and repercussions on male fertility.

Hypothyroidism and thyrotoxicosis are associated with male reproductive disorders, but little is known about the influence of the thyroid hormone milieu on seminal vesicle (SV) function and metabolism. In this sense, we investigated the effects of hypothyroidism and thyrotoxicosis induced in adulthood Wistar male rats on SV function and identified new thyroid hormone targets on male reproduction regulation using novel proteomic approaches. Hypothyroidism reduces SV size and seminal fluid volume, which are directly associated with low testosterone and estradiol levels, while thyrotoxicosis increases Esr2 and Dio1 expression in the SV. We found 116 differentially expressed proteins. Hypothyroidism reduces the expression of molecular protein markers related to sperm viability, capacitation and fertilization, protection against oxidative stress and energetic metabolism in SV, while it increases the expression of proteins related to tissue damage. In conclusion, thyroid dysfunction in the adult phase impairs several morphological, molecular and functional characteristics of SV.

Proteomic Profiles of Thyroid Gland and Gene Expression of the Hypothalamic-Pituitary-Thyroid Axis Are Modulated by Exposure to AgNPs during Prepubertal Rat Stages.

Silver nanoparticles (AgNPs) have potent antimicrobial activity and, for this reason, are incorporated into a variety of products, raising concern about their potential risks and impacts on human health and the environment. The developmental period is highly dependent on thyroid hormones (THs), and puberty is a sensitive period, where changes in the hormonal environment may have permanent effects. We evaluated the hypothalamic-pituitary (HP)-thyroid axis after exposure to low doses of AgNPs using a validated protocol to assess pubertal development and thyroid function in immature male rats. For stimulatory events of the HP-thyroid axis, we observed an increase in the expression of Trh mRNA and serum triiodothyronine. Negative feedback reduced the hypothalamic expression of Dio2 mRNA and increased the expression of Thra1, Thra2, and Thrb2 mRNAs. In the pituitary, there was a reduced expression of Mct-8 mRNA and Dio2 mRNA. For peripheral T3-target tissues, a reduced expression of Mct-8 mRNA was observed in the heart and liver. An increased expression of Dio3 mRNA was observed in the heart and liver, and an increased expression of Thrb2 mRNA was observed in the liver. The quantitative proteomic profile of the thyroid gland indicated a reduction in cytoskeletal proteins (Cap1, Cav1, Lasp1, Marcks, and Tpm4; 1.875 µg AgNP/kg) and a reduction in the profile of chaperones (Hsp90aa1, Hsp90ab1, Hspa8, Hspa9, P4hb) and proteins that participate in the N-glycosylation process (Ddost, Rpn1 and Rpn2) (15 µg AgNP/kg). Exposure to low doses of AgNPs during the window of puberty development affects the regulation of the HP-thyroid axis with further consequences in thyroid gland physiology.