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Environmental Factor, April 2015

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Pregnancy hormone plays a role in fetal response to hormone disruptors

By Kathleen Louden

Headshot of Jennifer Adibi

Adibi is a promising early-stage researcher, funded through the NIH Pathway to Independence Award program. (Photo courtesy of Jennifer Adibi)

Early exposure in the human womb to phthalates, which are common environmental chemicals, disrupts the masculinization of male genitals, according to an NIEHS-funded study that was presented March 8 at the Endocrine Society meeting in San Diego. Phthalates are hormone-altering chemicals, called endocrine disruptors, and are found in many plastics, containerized foods, and personal care products.

The clinical study confirms similar results of animal studies and provides new information about how phthalates target a main pregnancy hormone, said the lead scientist, Jennifer Adibi, Sc.D. of the University of Pittsburgh. 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.”

“Jennifer’s research has potential to be paradigm changing, because she is investigating the role of the placenta in mediating the effects of endocrine disruptors during early human development,” said Thad Schug, Ph.D., who oversees NIEHS grants related to reproduction and the endocrine system.

Linking phthalates, hCG, and human development

The researchers wanted to study whether phthalates disrupt male sexual differentiation and whether they do so by acting on hCG. They used an emerging biological marker of hormonal action in utero, the 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 used data from a multicenter NIEHS-funded study called The Infant Development and Environment Study, or TIDES, which studied a cohort of 780 pregnant women and their children from 2010 to 2013.

Sex-linked differences

By analyzing data from 362 women, Adibi and colleagues found that higher levels of hCG in the mothers’ blood were strongly associated with a shorter anogenital distance in male, but not female, babies.

Also, higher levels in mothers’ urine of two metabolites 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 an analytical method known as statistical causal inference, the investigators estimated the degree to which these chemicals affected anogenital distance by way of hCG. The researchers reported that in female babies, hCG explained about 8 percent of the effect of phthalates on the genitals, and in males, it was responsible for 20 to 30 percent. 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.

(Kathleen Louden is a contract writer for the Endocrine Society. This story is based on the Endocrine Society press release.)

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