Testicular aging, male fertility and beyond

Never before have parents in most Western societies had their first children as late as in recent decades. What are the central reasons for postponement? What is known about the link between the delay of childbearing and social policy incentives to counter these trends? This review engages in a systematic analysis of existing evidence to extract the maximum amount of knowledge about the reasons for birth postponement and the effectiveness of social policy incentives. The review followed the PRISMA procedure, with literature searches conducted in relevant demographic, social science and medical science databases (SocINDEX, Econlit, PopLine, Medline) and located via other sources. The search focused on subjects related to childbearing behaviour, postponement and family policies. National, international and individual-level data sources were also used to present summary statistics. There is clear empirical evidence of the postponement of the first child. Central reasons are the rise of effective contraception, increases in women's education and labour market participation, value changes, gender equity, partnership changes, housing conditions, economic uncertainty and the absence of supportive family policies. Evidence shows that some social policies can be effective in countering postponement. The postponement of first births has implications on the ability of women to conceive and parents to produce additional offspring. Massive postponement is attributed to the clash between the optimal biological period for women to have children with obtaining additional education and building a career. A growing body of literature shows that female employment and childrearing can be combined when the reduction in work-family conflict is facilitated by policy intervention.

The germline mutation rate in human males, especially older males, is generally much higher than in females, mainly because in males there are many more germ-cell divisions. However, there are some exceptions and many variations. Base substitutions, insertion-deletions, repeat expansions and chromosomal changes each follow different rules. Evidence from evolutionary sequence data indicates that the overall rate of deleterious mutation may be high enough to have a large effect on human well-being. But there are ways in which the impact of deleterious mutations can be mitigated.

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.