Faithful segregation of replicated chromosomes is essential for maintenance of genetic stability and seems to be monitored by several mitotic checkpoints. Various components of these checkpoints have been identified in mammals, but their physiological relevance is largely unknown. Here we show that mutant mice with low levels of the spindle assembly checkpoint protein BubR1 develop progressive aneuploidy along with a variety of progeroid features, including short lifespan, cachectic dwarfism, lordokyphosis, cataracts, loss of subcutaneous fat and impaired wound healing. Graded reduction of BubR1 expression in mouse embryonic fibroblasts causes increased aneuploidy and senescence. Male and female mutant mice have defects in meiotic chromosome segregation and are infertile. Natural aging of wild-type mice is marked by decreased expression of BubR1 in multiple tissues, including testis and ovary. These results suggest a role for BubR1 in regulating aging and infertility.

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BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice.

BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. METHODS A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n = 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. RESULTS A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93-1.43) for underweight, 1.11 (1.01-1.21) for overweight, 1.28 (1.06-1.55) for obese and 2.04 (1.59-2.62) for morbidly obese men. CONCLUSIONS Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further.

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BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis

Objectives—This report presents nationally representative estimates and trends for infertility and impaired fecundity—two measures of fertility problems—among women aged 15–44 in the United States. Data are also presented on a measure of infertility among men aged 15–44. Methods—Data for this report come primarily from the 2006–2010 National Survey of Family Growth (NSFG), which consisted of 22,682 interviews with men and women aged 15–44, conducted from June 2006 through June 2010. The response rate for women in the 2006–2010 NSFG was 78%, and for men was 75%. Selected trends are shown based on prior NSFG years. Results—The percentage of married women aged 15–44 who were infertile fell from 8.5% in 1982 (2.4 million women) to 6.0% (1.5 million) in 2006–2010. Impaired fecundity among married women aged 15–44 increased from 11% in 1982 to 15% in 2002, but decreased to 12% in 2006–2010. Among all women, 11% had impaired fecundity in 2006–2010. Both infertility and impaired fecundity remain closely associated with age for nulliparous women. Among married, nulliparous women aged 35–44, the percentage infertile declined from 44% in 1982 to 27% in 2006–2010, reflecting greater delays in childbearing over this period. Among married women in 2006–2010, non-Hispanic black women were more likely to be infertile than non-Hispanic white women. Some form of infertility (either subfertility or nonsurgical sterility) was reported by 9.4% of men aged 15–44 and 12% of men aged 25–44 in 2006–2010, similar to levels seen in 2002.

Infertility and impaired fecundity in the United States, 1982-2010: data from the National Survey of Family Growth.

Was human nature designed by natural selection in the Pleistocene epoch? The dominant view in evolutionary psychology holds that it was--that our psychological adaptations were designed tens of thousands of years ago to solve problems faced by our hunter-gatherer ancestors. In this provocative and lively book, David Buller examines in detail the major claims of evolutionary psychology - the paradigm popularised by Steven Pinker in The Blank Slate and by David Buss in The Evolution of Desire - and rejects them all. This does not mean that we cannot apply evolutionary theory to human psychology, says Buller, but that the conventional wisdom in evolutionary psychology is misguided. Evolutionary psychology employs a kind of reverse engineering to explain the evolved design of the mind, figuring out the adaptive problems our ancestors faced and then inferring the psychological adaptations that evolved to solve them. Evolutionary psychologists claim many discoveries based on this approach, including the evolutionary rationale for human mate preferences (that males prefer nubile females and females prefer high-status males) and "discriminative parental solicitude" (the idea that stepparents abuse their stepchildren at a higher rate than genetic parents abuse their biological children). In the carefully argued central chapters of Adapting Minds, Buller scrutinises several of evolutionary psychology's most highly publicised "discoveries." Drawing on a wide range of empirical research, including his own large-scale study of child abuse, he shows that none is actually supported by the evidence. Buller argues that our minds are not adapted to the Pleistocene, but, like the immune system, are continually adapting, over both evolutionary time and individual lifetimes. We must move beyond the reigning orthodoxy of evolutionary psychology to reach an accurate understanding of how human psychology is influenced by evolution. When we do, Buller claims, we will abandon not only the quest for human nature but the very idea of human nature itself.

Adapting Minds: Evolutionary Psychology and the Persistent Quest for Human Nature

This study compares the relative effects of advancing male age on multiple genomic defects in human sperm [DNA fragmentation index (DFI), chromatin integrity, gene mutations, and numerical chromosomal abnormalities], characterizes the relationships among these defects and with semen quality, and estimates the incidence of susceptible individuals for a well characterized nonclinical nonsmoking group of 97 men (22-80 years). Adjusting for confounders, we found major associations between age and the frequencies of sperm with DFI and fibroblast growth factor receptor 3 gene (FGFR3) mutations associated with achondroplasia (P < 0.01) with no evidence for age thresholds. However, we found no associations between age and the frequencies of sperm with immature chromatin, aneuploidies/diploidies, FGFR2 mutations (Apert syndrome), or sex ratio in this cohort. There were also no consistent correlations among genomic and semen-quality endpoints, except between DFI and sperm motility (r = -0.65, P < 0.001). These findings suggest there are multiple spermatogenic targets for genomically defective sperm with substantially variable susceptibilities to age. Our findings predict that as healthy males age, they have decreased pregnancy success with trends beginning in their early reproductive years, increased risk for producing offspring with achondroplasia mutations, and risk of fathering offspring with Apert syndrome that may vary across cohorts, but with no increased risk for fathering aneuploid offspring (Down, Klinefelter, Turner, triple X, and XYY syndromes) or triploid embryos. Our findings also suggest that the burden of genomic damage in sperm cannot be inferred from semen quality, and that a small fraction of men are at increased risk for transmitting multiple genetic and chromosomal defects.

https://www.pnas.org/content/pnas/103/25/9601.full.pdf

Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm

Background Although the effect of maternal age on fertility is well known, it is unclear whether paternal age also affects fertility. This cross-sectional study sought to characterize the association between age and semen quality, a well-known proxy of fertility status. Methods A convenience sample of 97 non-smoking men (aged 22-80 years) without known fertility problems was recruited from a national government laboratory. The men provided semen samples and information relating to lifestyle, diet, medical and occupational details. Semen volume (ml), sperm concentration (x10(6)/ml), total sperm count (x10(6)), motility (%), progressive motility (%) and total progressively motile sperm count (x10(6)) were measured. Results After adjusting for covariates, semen volume decreased by 0.03 ml per year of age (95% CI: -0.05, -0.01); motility decreased by 0.7% per year (95% CI: -0.92, -0.43); progressive motility decreased by 3.1% per year (95% CI: -4.5, -1.6); and total progressively motile sperm count decreased by 4.7% per year (95% CI: -7.2, -2.2). There was a suggested decrease in sperm concentration and count. The proportion of men with abnormal volume, concentration and motility was significantly increased across the age decades. Conclusions In a convenience sample of healthy men from a non-clinical setting, semen volume and sperm motility decreased continuously between 22-80 years of age, with no evidence of a threshold.

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The association of age and semen quality in healthy men

The objective of this report is to characterize the associations between age and semen quality among healthy active men after controlling for identified covariates. Ninety-seven healthy, nonsmoking men between 22 and 80 years without known fertility problems who worked for or retired from a large research laboratory. There was a gradual decrease in all semen parameters from 22-80 years of age. After adjusting for covariates, volume decreased 0.03 ml per year (p = 0.001); sperm concentration decreased 2.5% per year (p = 0.005); total count decreased 3.6% per year of age (p < 0.001); motility decreased 0.7% per year (P < 0.001); progressive motility decreased 3.1% per year (p < 0.001); and total progressively motile sperm decreased 4.8% per year (p < 0.001). In a group of healthy active men, semen volume, sperm concentration, total sperm count, and sperm motility decrease continuously between 22-80 years of age, with no evidence of a threshold.

/pdf/decreases-in-human-semen-quality-with-age-among-healthy-men-qnsn43em3s.pdf

L. Moore

Papers

The association of age and semen quality in healthy men

Decreases in Human Semen Quality with Age Among Healthy Men