Association of large scale 4977-bp "common" deletions in sperm mitochondrial DNA with asthenozoospermia and oligoasthenoteratozoospermia

Abstract

OBJECTIVE:To determine the association of large-scale mitochondrial DNA (mtDNA) deletions with abnormal sperm or abnormal flagellar movement of human spermatozoa in asthenozoospermia and oligoasthenoteratozoospermia (OAT) subjects using percoll gradients fractionation and long-range polymerase chain reaction (PCR).DESIGN:We investigated sixty infertile men and thirty normal healthy fertile controls. Of sixty infertile men, 39 were asthenozoospermia and 21 were OAT.MATERIALS AND METHODS:Percoll gradients discontinuous technique was used for separation of spermatozoa on the basis of their motility. Long-range PCR was used for detection of “common” 4977-bp deletions, and primer shift technique was used for confirmation of deletions.RESULTS:Overall fourteen subjects (14/60; 23.3%) of which eight (8/39; 20.5%) asthenozoospermia and six (6/21; 28.6%) OAT had shown deletions of 4977-bp. Deletions were more common (23.3%) in 40% fraction than 60% (11.6%) and 80% (5%) fractions. Sequencing results had shown deleted region of mtDNA.CONCLUSION:Abnormal spermatozoa had more number of mtDNA deletions than normal sperm, and abnormal spermatozoa had lost genes for the oxidative phosphorylation. Our findings suggest that large-scale 4977-bp mtDNA deletions in the spermatozoa from the infertile subjects cause the asthenozoospermic and OAT pathophysiological conditions in infertile males.

Sperm mitochondrial DNA measures and semen parameters among men undergoing fertility treatment

“…Next, to replicate findings from previous publications (Kao et al, 1995; 1998; St John et al., 2001; May-Panloup et al, 2003; Song and Lewis, 2008; Ieremiadou and Rodakis, 2009; Gholinezhad Chari et al., 2015; Ambulkar et al, 2016A; Ambulkar et al, 2016B; Zhang et al, 2016; Gabriel et al, 2012; Mughal et al, 2017; Bahrehmand Namaghi and Vaziri, 2017; Talebi et al, 2017), we examined the associations of mtDNAcn and mtDNAdel with semen parameters. The mean difference (MD) and 95% confidence intervals (CI) from the age and batch adjusted generalized linear models comparing semen parameter values by quartiles of sperm mtDNAcn and mtDNAdel are presented in Table 2.…”

“…Studies comparing sperm fractions based on motility from gradient centrifugation reported that, within individuals, sperm fractions with poorer motility have higher frequencies of mtDNA deletions compared with sperm fractions with higher motility (Kao et al, 1995; Kao et al, 1998; Ieremiadou and Rodakis, 2009; Gholinezhad Chari et al., 2015; Ambulkar et al, 2016a; 2016b), with one exception (St John et al, 2001), which may have been driven by a limited sample size. Similarly, studies of men from different geographic regions, including the USA (Song and Lewis, 2008), England (St John et al, 2001), Greece (Ieremiadou and Rodakis 2009), Taiwan (Kao et al., 1995; Kao et al., 1998), Turkey (Mughal et al, 2017), Iran (Bahrehmand Namaghi and Vaziri, 2017; Talebi et al, 2017), and India (Ambulkar et al, 2016A) reported that sperm mtDNAdel were more frequent among men classified as infertile based on abnormal semen parameters compared with men with normal semen parameters. Investigators of an Australian study, however, did not observe higher mtDNAdel among men with oligospermia or azoospermia compared with men with normospermia (Cummins et al, 1998).…”

Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility

“…If the mtDNA 4977 deletion occurs during spermatogenesis and/or spermiogenesis, the mature spermatozoa are endowed with dysfunctional mitochondria, which can act as a source of ROS. Interestingly, mtDNA 4977 has been recorded in the spermatozoa of infertile males with asthenozoospermia and oligoasthenozoospermia [148,149]. An alternative large-scale mtDNA deletion comprising 7436 bp (mtDNA 7436 ) has also been reported in low-motility human spermatozoa [150].…”

Yishentongluo decoction in treatment of idiopathic asthenozoospermia infertility

“…[ 9 – 15 ] Recently, mitochondrial dysfunction reported in AZS men came to attention, several studies reported this dysfunction is related to idiopathic asthenozoospermia, since sperm motility is regulated by intrinsic factors, and requires an appropriate supply of adenosine triphosphate. [ 16 – 18 ] For adenosine triphosphate synthesis, these gradients are generated by electron transfer maintained by the inner mitochondrial layer. Then energy storage in mitochondria is related to proton concentration and electric potential gradient in cell membrane.…”