Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring

Abstract

Over the last decade, there has been a significant increase in average paternal age when the first child is conceived, either due to increased life expectancy, widespread use of contraception, late marriages and other factors. While the effect of maternal ageing on fertilization and reproduction is well known and several studies have shown that women over 35 years have a higher risk of infertility, pregnancy complications, spontaneous abortion, congenital anomalies, and perinatal complications. The effect of paternal age on semen quality and reproductive function is controversial for several reasons. First, there is no universal definition for advanced paternal ageing. Secondly, the literature is full of studies with conflicting results, especially for the most common parameters tested. Advancing paternal age also has been associated with increased risk of genetic disease. Our exhaustive literature review has demonstrated negative effects on sperm quality and testicular functions with increasing paternal age. Epigenetics changes, DNA mutations along with chromosomal aneuploidies have been associated with increasing paternal age. In addition to increased risk of male infertility, paternal age has also been demonstrated to impact reproductive and fertility outcomes including a decrease in IVF/ICSI success rate and increasing rate of preterm birth. Increasing paternal age has shown to increase the incidence of different types of disorders like autism, schizophrenia, bipolar disorders, and childhood leukemia in the progeny. It is thereby essential to educate the infertile couples on the disturbing links between increased paternal age and rising disorders in their offspring, to better counsel them during their reproductive years.

Men without Sperms

“…Firstly, the 12.0% prevalence of azoospermia in the overall study group accords with the 10% -15% quoted by Gudeloglu and colleague [7] but much less than the 40% reported by Bashed et al [24] in Bangladesh. Earlier and recent studies have also shown decline in some semen quality with age [25] [26] such as lower ejaculate volume and sperm motility [27] [28] and increased paternal age with sperm quality [29]. There appears to be a phenomenon of gradual reduction in sperm quality of Africans as reported in a recent study [30].…”

Moving beyond a maternal perspective to child survival

“…As expected, there exists a strong correlation between maternal and paternal age at birth in VOLUME 53 __ OCTOBER 15, 2016 EDITORIAL India (r=0.72, P<0.0001) suggesting substantial residual confounding at the family/household level including support for a strong presence of assortative mating [11]. While it has been hypothesized that there may be mechanisms where paternal age could affect birth outcomes [17] (e.g., quality of sperm, epigenetic or DNA changes), it would mainly be observed among older males (>50 years) [18]. In the absence of any biologic mechanisms for younger fathers, we should expect the maternal effects to be much larger at younger ages.…”

D-Galactose-Induced Animal Model of Male Reproductive Aging

“…There were negative associations between increasing paternal age and reduction in testicular volume up to 31% and reduction testicular size. 10 This decreased testicular volume is also attributed to the decrease in number of spermatogenic and Sertoli cells. Histologically, degenerative changes in germinal epithelium and decreased number of Leydig cells can be observed.…”

“…Further, it has been shown that luteinizing hormone (LH) levels have a reverse relationship with serum testosterone levels in the case of aging. 10 The most scientists approve the free radicals/ oxidative stress theory that underlying many conditions related to aging process. This theory states that the age-related accumulation of free radicals and superoxide leads to damage of macromolecular components such as carbohydrates, lipids, proteins and nucleic acids which are the building blocks of cellular structure.…”