Teratozoospermia: Its association with sperm DNA defects, apoptotic alterations, and oxidative stress

Abstract

This study was carried out to evaluate the level of nuclear sperm DNA damage in men with isolated polymorphic teratozoospermia and examining its relationship with apoptosis and oxidative stress. A total of 89 subjects were divided into two groups: men with isolated teratozoospermia (n = 69) and men with normal semen parameters (n = 20) as controls. Sperm DNA breaks were determined by using acridine orange staining. The proportion of viable spermatozoa with mitochondrial transmembrane depolarization was detected by fluorescence microscopy through the use of MitoPTJC‐1 staining method. Bivariate Annexin V/6‐CFDA analysis was then set out in order to measure the percentage of both viable and dead spermatozoa with phosphatidylserine (PS) externalization. Seminal antioxidant profile (reduced glutathione (GSHr); oxidized glutathione (GSSG); glutathione S‐transferase (GST)) and total protein sulfhydryl (P‐SH) concentrations were measured spectrophotometrically. Men with isolated teratozoospermia, when compared to controls, showed significantly increased level of single sperm DNA breaks and higher proportions of spermatozoa with phosphatidylserine externalization and mitochondrial depolarization. Among the differently studied oxidative stress seminal parameters, the rates of seminal GSHr, GST, and P‐SH were significantly decreased in the teratozoospermic group. However, the seminal rates of GSSG and GST have decreased, but only GST did not show a significant difference. Interestingly, significant correlations were found between the studied apoptotic markers and the rate of atypical sperm forms with the incidences of head abnormalities. Furthermore, positive inter‐correlations were found between sperm DNA defects, impaired seminal antioxidant status, and the apoptotic sperm markers. Such data provide clear evidence that the apoptotic alterations are closely correlated to abnormal sperm morphology and DNA damage. Moreover, decreased seminal antioxidant profile may be a crucial factor involved in the mechanism of sperm cell death‐mediated DNA breaks in teratozoospermic semen.

Correlation among isolated teratozoospermia, sperm DNA fragmentation and markers of systemic inflammation in primary infertile men

“…The correlations between sperm morphology, sperm DNA integrity and oxidative balance have been recently investigated [ 13 , 27 , 28 ]. In this context, it has been observed that several conditions including inflammatory and infectious diseases may increase systemic and seminal OS, thus leading to impaired sperm morphology [ 29 – 31 ].…”

“…Agarwal et al suggested that spermatozoa with pathological morphology and activated leukocytes were the main source of ROS over-production in semen and that OS might further lead to structural cell defects [ 14 ]. Similarly, Ammar et al found that ROS generated from morphologically abnormal spermatozoa along with impaired seminal antioxidant defence may eventually induce many changes in sperm cells, thus including membrane and DNA damage and cell death [ 13 ].…”

“…As a whole, iTZS has been extensively associated with both spontaneous pregnancy and fertilization outcomes at assisted reproductive technology (ART), but results are mostly inconclusive [9,10,12]. Moreover, previous studies have investigated the relationship between iTZS and sperm DNA damage in males from the general population and in those with MFI [13][14][15]. Infertile men with iTZS showed greater prevalence of chromosomal abnormalities and higher DNA fragmentation indexes compared to controls [15,16].…”

“…Abnormal sperm morphology was also linked to increased levels of reactive oxygen species (ROS) in semen, thus contributing to sperm DNA damage [ 13 , 14 ]. Overall, published literature suggests that infertile men with iTZS have higher rates of sperm DNA fragmentation and imbalanced oxidative stress (OS) status than fertile controls.…”

The Effect of Teratozoospermia on Sex Chromosomes in Human Embryos

“…Over the last decade, cytogenetic investigations of severe teratozoospermia represented one of the most productive areas in the field of male infertility and assisted conception. [1][2][3][4] The effect of isolated teratozoospermia is controversial, with studies showing both improved 5 and worsened [6][7][8][9] assisted reproductive technology (ART) fertilization and/or pregnancy rates with in vitro fertilization outcome (IVF).…”