The analysis of mitochondrial DNA haplogroups and variants for in vitro fertilization failure in a Han Chinese population

Abstract

In this study, we aimed to investigate the associations of mitochondrial DNA (mtDNA) haplogroups and variants with in vitro fertilization (IVF) failure. A retrospective, comparative study of 260 fresh IVF cycles in a Han Chinese population was performed from July 2011 to April 2014. Seventy-three couples had low fertilization rates (≤30%) or total fertilization failure, and 187 controls with normal fertilization were included. Human sperm mtDNA haplogroups and variants were determined by polymerase chain reaction (PCR), nested PCR and direct sequencing. One unreported point variant, A15397G, and two novel deletions at positions 8270-8278 and 8276-8284 were found in this study. A homozygous variant, G9053A in MT-ATP6, was detected in 4 of the 73 cases with fertilization failure, whereas this substitution was not detected in the control group (p < 0.01). The frequency of the point 10397 homozygous variant in MT-ND3 in the IVF failure group was markedly lower than that in the control group (p < 0.05). Furthermore, this study showed that the frequencies of point 8701 and 8943 heterozygous variants in MT-ATP6 in the IVF failure group were also markedly lower than those in the control group (p < 0.05). In addition, the frequency of haplogroup Z was markedly higher in the IVF failure group than in the control group (p < 0.05). Our results suggested that MT-ATP6 variants might be possible causes of IVF failure, but the 10397 homozygous variant in MT-ND3 might help decrease the risk of developing IVF failure. Furthermore, this study indicated that men with haplogroup Z might inherit a higher risk of IVF failure in the Han Chinese population.

Forensic Relationship between ATP6 Gene and Sperm Motility in a Saudi Population

“…Those studies could support the application of mtDNA haplogroups of the infertile men in forensic caseworks. Mao et al (2016) revealed that males with haplogroup Z might accumulate a higher risk of in vitro fertilization failure in Han Chinese men group. Similarly, the present study revealed that the OAT of Saudi men could be found in H5a, M25 and U7 ATP6 haplogroups.…”

Association between sperm mitochondrial ND2 gene variants and total fertilization failure

“…In addition, MT-ND4 might be associated with Chinese male infertility (Ni et al 2017). Our previous study suggested that MT-ATP6 variants might be possible causes of IVF failure, but MT-ND3 homoplasmic variant 10397 might help decrease the risk of IVF failure (Mao et al 2015(Mao et al , 2016. In this study, we discuss the relationship between mitochondrial genes and fertilization failure, laying a foundation for studying the association between fertilization failure and the sperm MT-ND gene variants.…”

“…However, another study showed that the mtDNA haplogroup R was a strong, independent predictor of sperm motility in the Han Chinese population, conferring a 2.97-fold decreased chance of asthenozoospermia compared with those without haplogroup R (Feng et al 2013). In addition, our previous study indicated that men with haplogroup Z might inherit a higher risk of IVF failure in the Han Chinese population (Mao et al 2016). Haplogroups D and G are subgroups of haplogroup M, with diagnostic single-nucleotide polymorphism markers m.5178C>A and m.4833A>G, respectively.…”

“…The protocol for sperm preparation and total genomic DNA extraction was performed as described previously by our group (Mao et al 2015(Mao et al , 2016. The primer sequences, along with their nested PCR reaction conditions and GenBank Accession serial numbers, are shown in Table 6.…”

“…All sample genes underwent direct sequencing using 3730 DNA Sequencing Analysis Gene Mapper® Version 4.0 (Applied Biosystems, Foster City, CA, USA). In the forward and reverse sequencing of two positive sequences, if the second wave height was greater than 10% of the same site crest, it was considered a heteroplasmic variant (Lacan et al 2009;Kloss-Brandstätter et al 2010;Mao et al 2016).…”