Serum Concentrations of Estradiol and Free T₄ Are Inversely Correlated With Sperm DNA Damage in Men From an Infertility Clinic

Abstract

Sperm DNA damage adversely affects male fertility and contributes to poorer embryo development and lower pregnancy rates. Endogenous hormones are critical to spermatogenesis and maintenance of male reproductive function and likely play an important role in human sperm DNA integrity, but this relationship is not fully understood. The present study measured serum hormone levels and sperm DNA damage with the neutral comet assay in 362 male partners of infertile couples. When sperm concentration and other potential confounding variables were included in multiple linear regression, serum estradiol and free T 4 levels were inversely associated with sperm DNA damage. Among other statistically significant associations that were observed, an interquartile range (IQR) increase in estradiol was associated with a 6.3% decline (95% confidence intervals: 29.7%, 22.9%) in comet extent and a 16.2% (222.4%, 29.2%) decline in the percentage of DNA in the comet tail (Tail%), whereas an IQR increase in free T 4 was associated with a 24.4% (231.5%, 217.4%) decline in Tail%. Likewise, in multiple logistic regression, men in the highest estradiol quartile had an 81% reduced risk of having a comet extent value in the highest quartile compared with men in the lowest estradiol quartile. Men in the highest free T 4 quartile had 92% decreased odds of being categorized in the highest Tail% quartile compared with men in the lowest free T 4 quartile. These results suggest that estradiol and free T 4 may have a protective effect against sperm DNA damage, but future mechanistic and epidemiologic studies are needed to confirm these findings.

Exploratory analysis of urinary metabolites of phosphorus-containing flame retardants in relation to markers of male reproductive health

“…6 Despite the lack of correlation (r < 0.1) we recently reported between TPHP concentrations in house dust and DPHP concentrations in urine, 7 in the present study we found that urinary DPHP was associated with decreased sperm concentration and increased serum prolactin (though the association with prolactin was confounded by time of day of sample collection since prolactin levels are also higher in samples collected in the afternoon 20 ) in patterns consistent with our previous report on house dust concentrations of TPHP. 6 Although peculiar, there may be several possible explanations for consistent relationships between these endpoints and two exposure assessment approaches that were not correlated with one another: 1) the significant results for either house dust or urinary biomarker concentrations (or both) are due to chance findings; 2) Both TPHP and DPHP are bioactive, and there may be other uses (e.g., as a plasticizer) and sources of DPHP besides TPHP in house dust, 21 thus both measures may be associated with the same outcome measure but not with each other; 3) DPHP may be a metabolite of other chemicals in addition to TPHP (e.g., certain alkylated triphenyl phosphate isomers used as flame retardants, among others 22 ) that may be associated with these endpoints; 4) Since TPHP exposure may come from sources or locations outside the home (e.g., offices, automobiles), perhaps the two measures reflect differing aspects of exposure and both were associated with substantial but differing error in relation to true exposure.…”

Low 17beta-Estradiol Levels in Cnr1 Knock-Out Mice Affect Spermatid Chromatin Remodeling by Interfering with Chromatin Reorganization

“…In agreement, both antiestrogens and aromatase inhibitors have been reported to interfere with SPT elongation [46,47]. Furthermore, recent epidemiological studies showed that the serum concentrations of either estrogen and free thyroxine (T4) or estrogen and testosterone inversely correlated with sperm DNA damage in men [48,49].…”

“…Moreover, estrogens, directly or indirectly, affected SPZ chromatin acting on the testis rather than epididymis, since histone-to-protamine exchange takes place during spermiogenesis Overall, our results demonstrated that estrogens, indirectly via stimulatory effects on FSH secretion and/or directly via paracrine actions within the testis, play a key role in spermiogenesis. Interestingly, it is still a matter of debate whether FSH and/or estrogen affect chromatin remodeling in SPT in either a synergistic or an independent way with androgens [42,49,58,71,72]. However, the loss of Cnr1 did not impair fertility [15]: this likely occurs because of mechanisms of SPZ selection (Cnr1 À/À mice produce a sperm with heterogeneous histone content and chromatin quality) and/ or DNA repair operating in the female reproductive tract [73].…”

Relationship of seminal plasma antioxidants and serum male hormones with sperm chromatin status in male factor infertility

“…Intact sperm chromatin and sperm maturity are important for the reproductive potential of men [Meeker et al 2008]. Sperm chromatin damage negatively affects fertility potential and it may result in poor embryo quality with low pregnancy rates [Agarwal et al 2004; Lewis and Aitken 2005;Morris et al 2002].…”

“…Sperm chromatin damage may resolve as: i) oxidative stress (OS), ii) poor chromatin packaging or abnormal packing due to defective protamination, iii) abortive apoptosis, and iv) impairment in recombination during spermatogenesis resulting in cell apoptosis [Agarwal and Said 2003;Erenpreiss et al 2006;Sakkas et al 1999]. The most widely reported causes are OS, sperm nuclear protamination, and serum hormones [Appasamy et al 2007;Meeker et al 2008].…”