The hormone-altering chemicals known as phthalates are pervasive. They are found in many plastics, containerized foods, personalized hair products—and the placenta.

The placenta responds to phthalates by altering the levels of a key pregnancy hormone, human chorionic gonadotropin (hCG), and the consequences can be dire. For example, masculinization of male genitals can be disrupted, as measured by anogenital distance, the distance between the anus and the genitals. In men, a short anogenital distance is associated with decreased sperm count and infertility.

These findings emerged from research led by the University of Pittsburgh Graduate School of Public Health. The research suggests that clinical testing in pregnancy might look for early signs of chemical exposure. Doing so might guide interventions that could protect the health of the developing fetus.

Details of the research will be presented March 5 at the Endocrine Society’s 97th annual meeting in San Diego. The Endocrine Society has already posted the researchers’ abstract, which is entitled, “Placental Human Chorionic Gonadotropin Is Associated with Sex-Specific Development and the Response to Endocrine Disruptors.”

The abstract describes how researchers, led by Jennifer Adibi, M.P.H., Sc.D., assistant professor of epidemiology at Pitt Public Health, analyzed data collected from 362 women and their babies who participated in a multicenter investigation called The Infant Development and the Environment Study (TIDES). Between 2010 and 2012, the women gave blood and urine samples in their first trimester of pregnancy and allowed researchers to take measurements of the babies at birth.

Dr. 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 (MnBP) and monobenzyl phthalate (MBzP), 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% of phthalates' effect on the genitals and in males, it was responsible for 20–30%, the researchers reported. It is unclear why the effect varies by sex, Dr. Adibi said.

“For every log unit increase in urinary MEHP [or monoethylhexyl phthalate] and MnBP, male [anogenital distance] decreased by 1.2 mm,” noted the abstract. “If we administered a hypothetical substance that completely blocked the effect of hCG, then MEHP and MnBP would induce only a 0.87 mm and 0.99 mm decrease in AGD respectively.”

“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,” Dr. Adibi said. “There is growing societal concern over pediatric disorders that have a basis in the fetal period and which may be more common in one sex or another, such as autism, attention deficit disorder, obesity, asthma, and infertility. It is important to find out if chemicals in our food or environment might influence these conditions.”

Dr. Adibi elaborated on the findings in a video that was posted to YouTube.

“The early placenta is a site of endocrine disruption, and a contributor to the development of the fetal genitalia.  hCG may partially mediate the effects of phthalates on fetal genitalia,” the abstract concluded. “By monitoring of first trimester hCG, normalized by fetal sex, we may have the opportunity to identify abnormal development, intervene, and improve the health of the child.”

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