Abstract
Cryptorchidism, registered at birth or later, is the most common birth defect in males in western countries, estimated to affect around 2–3% of newborn boys, declining to around 2% at 3 months. We have previously described a potential association between stressful life events (SLEs) in pregnancy and reduced semen quality and testosterone levels in adult offspring. Both outcomes are believed to share a common etiology with cryptorchidism thus increased risk of cryptorchidism in boys exposed to prenatal SLEs may be plausible. The risk of cryptorchidism associated with prenatal SLE amongst 1,273 male Generation 2 offspring was estimated using the Western Australian Pregnancy (Raine) Study. SLEs are discrete experiences that disrupt an individual's usual activities causing a life change and readjustment, such as death of a relative or friend, divorce, illness or job loss. Mothers prospectively reported SLEs, during pregnancy at gestational weeks (GW) 18 and 34 using a standardized 10-point questionnaire. A boy was diagnosed as cryptorchid if one or both testes was non-palpable in the scrotum and not able to be manipulated into the scrotum. Twenty-four (2%) cryptorchid boys were identified. Mean (standard deviation) of SLE exposures in GW34 was 1.1 (1.2) for non-cryptorchid boys and slightly higher 1.5 (1.8) for cryptorchid boys, similar differences were observed in GW18. Adjusted odds ratio [OR] and 95% confidence intervals (CI) for risk of cryptorchidism in early (18-weeks) and late gestation (34-weeks) according to prenatal SLE exposures were: 1.06 (95% CI: 0.77–1.45) and 1.18 (95% CI: 0.84–1.67), respectively. This is the first-time report on the possible relationships between exposure to early and late pregnancy SLEs and risk of cryptorchidism in a birth cohort. Prenatal SLE exposure was not associated with a statistically significant increase in the risk of cryptorchidism in male offspring. A small case population limits the statistical power of the study and future larger studies are required to evaluate this potential association.
Highlights
Cryptorchidism is the most common anomaly in males in western countries and is estimated to affect around 2–3% of full-term newborn boys, declining to around 2% at 3 months [1]
We have previously described a potential association between exposure to maternal stressful life events (SLEs) in pregnancy and reduced semen quality and testosterone levels in the male offspring in adulthood [16], we hypothesize that maternal SLE exposures may increase the risk of cryptorchidism as these outcomes are considered symptoms of disrupted development of the reproductive system [3, 17]
A significantly higher proportion of cryptorchid boys were exposed to the SLE “Death of a relative” reported at GW18 as well as “partners involuntary job loss” and “money problems” reported in the GW34 (Table 1)
Summary
Cryptorchidism is the most common anomaly in males in western countries and is estimated to affect around 2–3% of full-term newborn boys, declining to around 2% at 3 months [1]. Non-chemical exposures, including stressful life events (SLEs), may disrupt the prenatal hormonal milieu as well and gestational exposure to SLEs has been identified as having deleterious reproductive effects on human male fetuses [11]. This is supported by animal studies which suggest that stressors (such as prenatal restraint of the animal) during pregnancy can affect reproductive function in male offspring including delayed testicular descent [12,13,14,15]
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