Early Life Events Predict Adult Testicular Function; Data Derived From the Western Australian (Raine) Birth Cohort

Abstract

Exposures to maternal smoking and higher cord blood estrogens at delivery were associated with a reduced sperm output in adulthood. Optimal adult testicular function depends on being born at or above average weight, and maintaining optimal growth and adiposity into adulthood.

The Early Life Influences on Male Reproductive Health

“…In a cohort of Australian men followed from birth, men born with gestational appropriate birth weights were significantly less likely to be grouped in the lowest quartile for their total motile sperm counts. Those men who were born preterm demonstrated reduced serum testosterone levels in adulthood, suggesting an adverse influence of growth restraint and prematurity on later life testicular function [41]. A prospective Danish birth cohort study of more than 2500 live born males found statistically significant associations between cryptorchidism and low birth weight, prematurity, being small for gestational age, substantial vaginal bleeding in pregnancy and breech presentation, which is in accordance with other studies [42].…”

“…The first study to formally examine the association of maternal oestrogen exposure on male reproductive development was a longitudinal cohort study of almost 400 adult males. It found that sperm output in adulthood was inversely correlated with cord serum oestradiol and oestrone [41]. Furthermore it has been reported that oestrogenic chemical exposure can also cause cryptorchidism [9].…”

“…Exposure to cigarette smoking in utero has consistently been shown to negatively impact on male reproductive development, and in fact maternal smoking exposure during pregnancy may have a stronger effect on subsequent spermatogenesis than a man's own smoking in later life [8]. Reductions in median sperm output and total motile sperm are evident, and substantial [41]. One Danish cross-sectional study showed maternal smoking during pregnancy to be associated with earlier onset of puberty, lower final adult height, higher BMI, reduced testicular volume, lower total sperm count, reduced spermatogenesis-related hormones (inhibin-B and FSH) and higher free testosterone [55].…”

“…A relationship between increasing incidence of disorders of development of the male reproductive tract, declining sperm counts and exposure to exogenous oestrogen in utero has been postulated for many years [53]. Animal studies have previously shown that exposure to exogenous oestrogens [60,61] and environmental xenoestrogens [61,62] can damage testicular function, however concern that ubiquitous and increasing global oestrogen pollution may have effect on testicular function have so far been unconfirmed by the lack of alteration in domestic animal sperm production over the past century [41,63]. Hence this view does have its detractors [64].…”

Experimentally induced testicular dysgenesis syndrome originates in the masculinization programming window

“…Moreover, testing whether such adult-onset disorders originate in fetal life is challenging in humans, as it requires "looking back in time" over 20 or more years (2,11). Consequently, the TDS hypothesis remains largely untested and unproven (12,13), although circumstantial supporting evidence from clinical studies has grown progressively (1,3,5,14,15). If the TDS hypothesis was proved correct, it would refocus research effort in humans toward identifying causal factors acting via the pregnant mother that might be preventable.…”