Methods of Assisted Reproduction May Be Connected to Risk of Using Sperm with Impaired DNA Integrity

That Can Lead to Spontaneous Abortion or Delivery of a Child With Congenital Abnormalities

Przegl Lek. 2006;63(9):800-2.Links
[Influence of DNA damage on fertilizing capacity of spermatozoa][Article in Polish]


Sikora J, Kempisty B, Jedrzejczak P, Jagodziński PP.
Katedra i Zakład Biochemii i Biologii Molekularnej Akademii Medycznej im. K. Marcinkowskiego w Poznaniu.

DNA damage in the male germ line cells is correlated with male infertility. Nuclear DNA damage in mature sperm includes single strand nicks and double strand breaks that can arise as a consequence of errors in chromatin rearrangement during spermiogenesis, abortive apoptosis, and oxidative stress. Methods of assisted reproduction may be connected with a risk of the using of sperm with impaired DNA integrity that can lead to spontaneous abortion or delivery of a child with congenital abnormalities.

-------------------------------------------------------------------------------------


1: Asian J Androl. 2006 Jan;8(1):11-29. Links
Sperm chromatin structure and male fertility: biological and clinical aspects.Erenpreiss J, Spano M, Erenpreisa J, Bungum M, Giwercman A.
University of Lund, Fertility Centre, Malmö University Hospital, Malmö SE 205 02, Sweden. Juris.Erenpreiss@med.lu.se

Sperm chromatin/DNA integrity is essential for the accurate transmission of paternal genetic information, and normal sperm chromatin structure is important for sperm fertilizing ability. The routine examination of semen, which includes sperm concentration, motility and morphology, does not identify defects in sperm chromatin structure. The origin of sperm DNA damage and a variety of methods for its assessment are described. Evaluation of sperm DNA damage appears to be a useful tool for assessing male fertility potential both in vivo and in vitro. The possible impact of sperm DNA defects on the offspring is also discussed.

PMID: 16372115 [PubMed - indexed for MEDLINE]


------------------------------------------------------------------------------------



Genomics. 2002 Jan;79(1):58-62. Links
Paternal origins of complete hydatidiform moles proven by whole genome single-nucleotide polymorphism haplotyping.Fan JB, Surti U, Taillon-Miller P, Hsie L, Kennedy GC, Hoffner L, Ryder T, Mutch DG, Kwok PY.
Affymetrix, 3380 Central Expressway, Santa Clara, CA 95051, USA.

Complete hydatidiform moles (CHMs) are diploid tumors that result from fertilization of an empty ovum by a haploid 23,X sperm. In most cases, the resulting duplication of the genome gives rise to a 46,XX genotype and is thought to be androgenetic in origin. If this hypothesis is correct, then the genotypes of all polymorphic markers in CHMs should be homozygous. We used a dense set of single-nucleotide polymorphism (SNP) markers, evenly spaced throughout the genome, to definitively test this hypothesis. We genotyped genomic DNA samples from five CHMs and their corresponding maternal samples with 1494 SNP markers using high-density microarrays (HuSNP). As predicted, the maternal samples were heterozygous at >25% of the markers, which is consistent with the expected average heterozygosity of this panel of SNPs. In contrast, the five CHM samples were heterozygous at <0.75% of the SNP markers, which shows that these diploid tumors consist of a duplicated set of chromosomes. Because the CHM genotypes represent the haplotypes of their genomes, our results show that long-range haplotypes can be obtained easily with this resource and that a collection of such samples is a simple way to obtain reference haplotypes for association studies in various populations.

PMID: 11827458 [PubMed - indexed for MEDLINE]

CNVs in spermatozoa or other germ cells?

"CNVs can also be involved in disease indirectly by influencing gene expression through positional effects. The change may be quite distant from a disease-causing gene, but it could adversely influence its expression. The presence of a CNV may also alter the architecture of the genome such that it is more prone to further changes to occur in subsequent mitoses or meioses."

We are just seeing the tip of the iceberg. Certainly to best understand possible complexities, CNV-type investigations should be incorporated into all genetic studies going forward… at least I would hope so.








CNVs in spermatogonia and/or other germ cells?

HI,

That is a very interesting line of research. I am not aware of any groups doing this kind of work (CNVs in spermatozoa or germ cells).

Thanks,

Armand Zini



CMAJ • August 29, 2006; 175 (5). doi:10.1503/cmaj.060218.
© 2006 CMA Media Inc. or its licensors




--------------------------------------------------------------------------------
Review

Sperm DNA damage: clinical significance in the era of assisted reproduction
Armand Zini and Jamie Libman
From the Division of Urology, Department of Surgery, McGill University, Montréal, Que.

Correspondence to: Dr. Armand Zini, Rm. 2304, St. Mary's Hospital, 3830 Lacombe Ave., Montréal QC H3T 1M5; fax 514 734-2718; armand.zini@ssss.gouv.qc.ca

Abstract

Evidence suggests that damage to human sperm DNA might adversely affect reproductive outcomes and that the spermatozoa of infertile men possess substantially more sperm DNA damage than do the spermatozoa of fertile men. This is particularly relevant in an era where advanced forms of assisted reproductive technologies are commonly used (technologies that often bypass the barriers to natural selection), because there is some uncertainty regarding the safety of using DNA-damaged spermatozoa. In this review, we outline our current understanding of how sperm DNA is organized, what causes sperm DNA damage, what impact this damage may have on reproductive capacity and whether tests of sperm DNA damage are clinically useful.



Zini, Armand M.D.


Clinical Interest : Male Infertility
Research Interest : Sperm DNA integrity
Semen oxidants
Varicocele
Undergraduate studies : Mariannopolis College
Health Sciences
1980-1982

McGill University
B.Sc. in Biochemistry
1982-1985
Medical school :
McGill University
1985-1989


Urology Training :
McGill University
1989-1994
Fellowship : Cornell University, New York
Male Infertility
1994-1996
Current Appointment : Associate Professor
Department of Surgery

Grants Currently Held : Physicians Services Incoporated, Ontario
Current Address : St. Mary's Hospital
3830 Lacombe
Montreal, Quebec
Tel: (514) 345-3511 ext:3282

DELETIONS

Small deletions are less likely to be fatal; large deletions are usually fatal - but always, there is variation based on what genes are lost. Some medium-sized deletions lead to recognizable human disorders.Deletion of a number of base pairs that is not evenly divisible by three will lead to a frameshift mutation, causing all of the codons occurring after the deletion to be read incorrectly during translation, producing a severely altered and potentially nonfunctional protein.

Deletions are responsible for an array of genetic disorders, including some cases of male infertility and two thirds of cases of Duchenne muscular dystrophy.[1] A deletion of part of the short arm of chromosome 5 results in a syndrome called Cri du chat,[1] also known as "cry of the cat" syndrome. It is found in approximately 1 in 50,000 live births. The surviving infants have a distinctive cry, severe mental retardation, and shortened life span.