New observations on maternal age effect on germline de novo mutations

Abstract BACKGROUND The effect of maternal age at conception on various aspects of offspring health is well documented and often discussed. We seldom hear about the paternal age effect on offspring health, although the link is now almost as solid as with maternal age. The causes behind this, however, are drastically different between males and females. CONTENT In this review article, we will first examine documented physiological changes linked to paternal age effect. We will start with all morphological aspects of the testis that have been shown to be altered with aging. We will then move on to all the parameters of spermatogenesis that are linked with paternal age at conception. The biggest part of this review will focus on genetic changes associated with paternal age effects. Several studies that have established a strong link between paternal age at conception and the rate of de novo mutations will be reviewed. We will next discuss paternal age effects associated with telomere length and try to better understand the seemingly contradictory results. Finally, severe diseases that affect brain functions and normal development have been associated with older paternal age at conception. In this context, we will discuss the cases of autism spectrum disorder and schizophrenia, as well as several childhood cancers. SUMMARY In many Western civilizations, the age at which parents have their first child has increased substantially in recent decades. It is important to summarize major health issues associated with an increased paternal age at conception to better model public health systems.

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MATERNAL AGE EFFECT ASSOCIATED WITH YELLOW PIGMENT IN MALPIGHIAN TUBES OF DROSOPHILA MELANOGASTER

Canadian Journal of Genetics and Cytology ◽

10.1139/g73-054 ◽

1973 ◽

Vol 15 (3) ◽

pp. 437-442 ◽

Cited By ~ 1

Author(s):

Harry Nickla

Keyword(s):

Maternal Age ◽

Opposite Effect ◽

Age Effect ◽

Yellow Pigment ◽

Medium Effect ◽

Young Females ◽

Maternal Age Effect ◽

Related Compounds ◽

Pigment Accumulation ◽

Rna And Dna

Using chromatographic and fluorometric methods a maternal age effect was demonstrated which involves yellow pigment accumulation in the Malpighian tubes of light (lt) flies. As age of females (lt+/lt and lt/lt) increases, yellow pigment accumulation in lt/lt offspring increases. The influence of maternal age is most dramatic in young females aged 1 to 5 days prior to mating. In addition, fertility decreases as maternal age increases. A medium effect was noted whereby females reared on fresh medium produce lt/lt offspring with slightly more yellow pigment in their Malpighian tubes than offspring of females reared on "worked" medium. The opposite effect was observed for fertility. Results are discussed in terms of accumulation of pteridines (and closely related compounds) as females age and changes in RNA and DNA content in the eggs of aging females.

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Maternal age effect on early human embryonic development and blastocyst formation

Molecular Reproduction and Development ◽

10.1002/(sici)1098-2795(199609)45:1<31::aid-mrd4>3.0.co;2-t ◽

1996 ◽

Vol 45 (1) ◽

pp. 31-37 ◽

Cited By ~ 109

Author(s):

Laurent Janny ◽

Yves J.R. Menezo

Keyword(s):

Embryonic Development ◽

Maternal Age ◽

Age Effect ◽

Blastocyst Formation ◽

Maternal Age Effect ◽

Early Human

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Parental Age and Schizophrenia

The British Journal of Psychiatry ◽

10.1192/bjp.112.490.899 ◽

1966 ◽

Vol 112 (490) ◽

pp. 899-905 ◽

Cited By ~ 22

Author(s):

K. L. Granville-Grossman

Keyword(s):

Maternal Age ◽

Age Effect ◽

Age Effects ◽

Paternal Age ◽

Considerable Importance ◽

Parental Age ◽

Advanced Paternal Age ◽

Older Parents ◽

Maternal Age Effect ◽

Environmental Causes

Reports that schizophrenics have older parents than non-schizophrenics (Barry, 1945; Goodman, 1957; Johanson, 1958; Gregory, 1959) are of considerable importance. If valid, they provide evidence for environmental causes of schizophrenia, and by analogy with other conditions where parental age effects have been noted may give some indication of the nature of these causes. There are, however, inconsistencies in these studies: thus Johanson and Gregory found a significant association between advanced paternal age and schizophrenia, but failed to confirm the maternal age effect noted by Barry and Goodman. These differences indicate the need for further investigation and this paper describes such a study.

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The difficulties in establishing a birth order or maternal age effect in ankylosing spondylitis: Comment on the article by Baudoin et al

Arthritis & Rheumatism ◽

10.1002/art.505 ◽

2002 ◽

Vol 46 (2) ◽

pp. 563-564 ◽

Cited By ~ 2

Author(s):

William H. James

Keyword(s):

Ankylosing Spondylitis ◽

Birth Order ◽

Maternal Age ◽

Age Effect ◽

Maternal Age Effect

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Inverse maternal age effect in monosomy X

Human Genetics ◽

10.1007/bf00287168 ◽

1979 ◽

Vol 51 (2) ◽

pp. 147-151 ◽

Cited By ~ 21

Author(s):

T. Kajii ◽

K. Ohama

Keyword(s):

Maternal Age ◽

Age Effect ◽

Monosomy X ◽

Maternal Age Effect

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Variations in the Maternal Age Effect on Twinning Rates: The Nordic Experience

Twin Research and Human Genetics ◽

10.1375/twin.8.5.515 ◽

2005 ◽

Vol 8 (5) ◽

pp. 515-523 ◽

Cited By ~ 16

Author(s):

Johan Fellman ◽

Aldur W. Eriksson

Keyword(s):

World War Ii ◽

20Th Century ◽

Maternal Age ◽

Regression Line ◽

Temporal Trends ◽

Age Distribution ◽

Age Effect ◽

Strongly Correlated ◽

Maternal Age Effect ◽

Increasing Trends

AbstractMaternal age is the most important nongenetic factor influencing the twinning rate. Every study of the effect of other factors should consider the age distribution of the mothers. Besides standardizing techniques, the age-specific twinning rates are analyzed. Especially, the slope of the regression line is considered when the age-specific twinning rates are regressed against maternal age. How well the maximum age-specific twinning rate measures the variation in the maternal age effect is also studied. The two measures, which are strongly correlated, give consistent results. The proposed methods are applied to data from Finland (1866 to 2003) and Denmark (1855 to 2000). Comparisons with Sweden (1861 to 2000) and Norway (1855 to 2003) are also made. In general, marked decreasing trends in the twinning rates are discernible up to the middle of the 20th century. In Sweden the decline starts around the beginning of the 20th century and is stronger than in Denmark and Norway. The decrease in the twinning rate for Finland, which up to World War II was rather isolated, sets in around the middle of the 20th century and is not as strong as in other Nordic countries. After the minima around 1980, strong increasing trends are noted. This is mainly caused by the influence of the artificial reproduction technologies and particularly the use of fertility-enhancing drugs on the commonly noted dependence between maternal age and the twinning rate. Similar temporal trends can be observed in the slopes of the regression line and in the maximum age-specific twinning rates.

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