BEST OF ESHRE & ASRM 2019

Phthalate exposure and anomalies in male reproductive health

Published 27 March 2019

The threat posed to humans, animals and the environment by plastic pollution dominates global discourse. But it is not just the plastics themselves that are a hazard. The hormone-disrupting abilities of the chemicals used in them, as in countless common household items, may have consequences for male reproductive development.

A growing body of evidence, as outlined by Shanna Swan from the Icahn School of Medicine at Mount Sinai, New York, shows that boys born to women with high levels of phthalates (added to plastics to increase durability) detected in their urine during pregnancy have reduced anogenital distance (AGD, the distance between the anus and underside of the scrotum). A measurement below two inches (5.08 cm) is a known predictor of low sperm count, and in 2011 Swan's group established a clear link between short AGD and reduced semen quality in young adults.

Falling sperm counts
Systematic reviews of data seem to show a consistent decline in semen quality among men in Western countries. Swann's estimate, from analysing 'thousands of papers', is an overall decline in sperm count of around 1% a year - 'without any indication things were tapering off.'

So the next focus of her work was identifying why. Rising testosterone levels trigger the start of male and female differentiation at around day 18 and 21 of development. This marks the beginning of penis and gonad development along with AGD lengthening, and adequate prenatal testosterone is 'critical', said Swan.

Phthalate exposure
However, studies in rats had demonstrated that anti-androgenic chemicals including phthalates have the ability to lower testosterone levels, or even inhibit its release completely. The resulting 'phthalate syndrome' shortens male AGD and triggers anomalies such as a malformed penis and cryptorchidism. Swan described how phthalate syndrome bears many similarities to testicular dysgenesis syndrome (TDS), where short AGD and poor semen quality are apparent, suggesting a common fetal origin.

Swan, working with the Study for Future Families, investigated the effect of prenatal phthalate exposure on infant genital development in a 2005 study in which mid-gestation urine samples were correlated with AGD, penile width and scrotal size.(1) Results showed that women exposed to the highest quartile of phthalate metabolite had a 13-times greater risk of having a boy with shorter than expected AGD. The risk was five times greater for those in the middle quartile. Penile width and testicular descent were also associated with phthalate exposure and scrotal size.

Further research for the Infant Development and the Environment Study (TIDES) published in 2015 confirmed the first trimester of pregnancy as most sensitive to exposure.(2) A total of 753 infants with first trimester phthalate exposure had their AGD and penis measured at birth and at one year, with results demonstrating an inverse correlation with phthalate concentration. 'We concluded that AGD was a reliable biomarker, repeatable and related to androgen exposure,' said Swan. The suggestion was that even at current low levels environmental exposure to phthalates can adversely affect male genital development, with implications for later reproductive health.

This was indicated in a study performed by Swan in unselected male students in 2011 in which AGD was a strong correlate of all semen parameters and a predictor of low sperm concentration.(3) Thus, in terms of male fertility, AGD does appear to matter, with environmental factors including phthalates an emerging culprit in developmental and reproductive toxicity.

1. Swan SH, Main KM, Liu F, et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect 2005; 113: 1056–1061.

2. Swan SH, Sathyanarayana S, Barrett ES, et al. TIDES Study Team . First trimester phthalate exposure and anogenital distance in newborns. Hum Reprod. 2015;30(4):963–972.

3. Mendiola J, Stahlhut RW, Jørgensen N, et al. Shorter anogenital distance predicts poorer semen quality in young men in Rochester, New York. Environ Health Perspect 2011; 119: 958–963.

SPERM COUNT

The decline in sperm count has become steeper since 2000

CAMPUS: MALE INFERTILITY

Many more questions than answers at male reproductive health Campus meeting