Abstract
The aim of this study wasto assess the in vitro effects of levothyroxine (LT4) on conventional and bio-functional sperm parameters and its implications on fertility. Patients with male idiopathic infertility were enrolled and subjected to examination of the seminal fluid and capacitation according to the WHO 2010 criteria and flow cytometric sperm analysis for the evaluation of bio-functional sperm parameters. LT4 significantly increased the percentage of spermatozoa with high mitochondrial membrane potential (MMP), decreased the percentage of spermatozoa with low MMP and increased sperm motility already at a concentration of 0.9 pmol L−1. Therefore, LT4 significantly reduced sperm necrosis and lipid peroxidation ameliorating chromatin compactness. These effects of LT4 were evident at a concentration of 2.9 pmol L−1, close to the physiological free-thyroxine (FT4) concentrations in the seminal fluid of euthyroid subjects. We showed a beneficial role of thyroid hormones on sperm mitochondrial function, oxidative stress and DNA integrity. The results of this in vitro study could have a clinical application in patients with idiopathic infertility, clarifying the role of thyroid function on male fertility.
Highlights
It is known that the thyroid hormones (THs), 3,5,3 -triiodothyronine (T3) and thyroxine (T4) impact the reproductive function, and thyroid dysfunction is associated with an adverse effect on fertility, both in men [1,2] and women [3]
We showed a beneficial role of thyroid hormones on sperm mitochondrial function, oxidative stress and DNA integrity
Our study investigated the 4i.nDviistrcousesffieocnts of LT4 on human sperm motility and bio-functional sperm parameters at physiological concMenatnraytiaosnpsecats omfetahseupreodssinblethreolseemofinTaHlsflauriedy, eftortothbe cfilrasrtiftieimd.eO. uAr csctourddyininglvye,swtigeatseedletchteedina vpihtryosieoffloecgtiscaolf dLoTs4eo(2n.9hupmaonl Lsp−1e)rmof mLTo4tilaintydacnodncbeino-tfruanticotniosnraelspspeectrimveplyarlaomwetre(r0s.9atppmhoylsiLo−lo1)giacnadl choingcheenrt(r9a.t9iopnms oalsLm−1e)afosurroeudr in vtihteroseexmpienraiml eflnutisd. , for the first time
Summary
It is known that the thyroid hormones (THs), 3,5,3 -triiodothyronine (T3) and thyroxine (T4) impact the reproductive function, and thyroid dysfunction is associated with an adverse effect on fertility, both in men [1,2] and women [3]. Hypothyroidism shows sperm abnormalities partly similar to those reported in hyperthyroidism with an arrest of spermatogenesis, reduction of sperm vitality and an increase of oxidative stress with lipid peroxidation [4,8,9], as well as asthenozoospermia in humans [7]. These semen alterations are reversible both in hypo- and hyperthyroidism and disappear upon achieving euthyroidism [7]. The role of THs on male reproductive function and on sperm parameters is still unclear and the scientific evidence is conflicting. All in vitro studies have been performed on animal models; no study has addressed bio-functional and conventional sperm parameters regarding humans
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