Prenatal exposure to common chemical, phthalates, found in some plastics disrupts masculinization of male genitals

Phthalates are hormone-altering chemicals, called endocrine disruptors, and are found in many plastics, containerized foods and personal care products.

The clinical study not only confirms similar results of animal studies, it also provides new information about how phthalates target a main pregnancy hormone, said the principal investigator, Jennifer Adibi, MPH, ScD, assistant professor, University of Pittsburgh Graduate School of Public Health. This hormone, known as human chorionic gonadotropin (hCG), is made during pregnancy by the placenta and can be measured in the mother's blood and urine.

"The placenta, which is an extension of the fetus and a target of the chemicals in our bodies, broadcasts information early in pregnancy, through hCG, about what might be occurring to the fetus (from) chemical exposure," Adibi said. "We may be able to act on this information to protect the pregnancy and the long-term health of the future child."

The researchers wanted to show whether prenatal exposure to phthalates, which block the male hormone testosterone, disrupts male sexual differentiation and whether they do so by acting on hCG. They used a newer biological marker of hormonal action in utero: anogenital distance at birth, which is the distance between the anus and the genitals. Studies in male animals and in young men show that a longer anogenital distance correlates with better fertility and that a short anogenital distance is strongly associated with greater risk of a low sperm count.

Adibi and her co-workers conducted their research using data from a multicenter study called The Infant Development and the Environment Study, or TIDES. The National Institute of Environmental Health Sciences funded Adibi's work and TIDES, which was performed from 2010 to 2013 in 780 pregnant women and their children. Women gave blood and urine samples in their first trimester of pregnancy and allowed researchers to take measurements on the babies at birth.

The new research analyzed data from 362 women. Adibi and colleagues found that higher levels of hCG in the mothers' blood were strongly associated with a lower anogenital distance in male babies (specifically the distance from the anus to the scrotum), but not in female infants.

Also, higher levels in mothers' urine of two metabolites (residues) of a prevalent phthalate, mono-n-butyl phthalate and monobenzyl phthalate, were strongly associated with lower levels of hCG in women carrying male babies and with higher hCG levels in those carrying female babies.

Using statistical causal inference, the investigators estimated the degree to which these chemicals affected the infants' anogenital distance by way of hCG. In female babies, hCG explained about 8 percent of phthalates' effect on the genitals and in males, it was responsible for 20 to 30 percent, the researchers reported. It is unclear why the effect varies by sex, Adibi said.

"Our study is the first to show that hCG is a target of phthalate exposure in early pregnancy and to confirm previous findings that it is a critical hormone in male development," Adibi said. "Increased knowledge of placental hormones and their relationships to the baby's health may one day improve our ability to detect fetal abnormalities earlier in pregnancy," she said.