The Endocrine Society

The Endocrine Society

Perspective from Michael L. Eisenberg, MD
March 05, 2015
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Secreted placental hormones could help identify fetal abnormalities related to EDCs in both sexes

Perspective from Michael L. Eisenberg, MD
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SAN DIEGO — Human chorionic gonadotropin could partially mediate the effects of endocrine-disrupting phthalates on female genitalia sustained in the womb, according to research presented at The Endocrine Society annual meeting.

Monitoring human chorionic gonadotropin (hCG) in the first trimester of pregnancy, with normalization for fetal sex, could allow clinicians to identify abnormal development and intervene, according to researchers.

“It offers a possibility to better utilize secreted placental hormones in the first trimester to gauge normal vs. abnormal sex-specific fetal development, which could have implications for clinical practice, population monitoring and epidemiologic research,” Jennifer Joan Adibi, MPH, ScD, of the University of Pittsburgh, said during a press conference.

In a multicenter prospective cohort of 362 pregnant women, Adibi and colleagues evaluated the relationships of hCG with anogenital distance (AGD) in both male and female neonates, and with urinary phthalates. The investigators also explored whether phthalates, through their action on hCG, disrupt male sexual differentiation.

The researchers measured phthalates and hCG in urine and serum samples, respectively, obtained during the first trimester. Trained study staff performed neonatal exams.

The investigators used multivariate linear regression to estimate sex-specific associations of the placental hormones with AGD in males (AS, anus to scrotum; AP, anus to penis) and females (AF, anus to fourchette; AC, anus to clitoris).

The same method was used to gauge birth weight for gestational age by z-score, and urinary concentrations of five phthalates — mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), monoethylhexyl phthalate (MEHP) and monoethyl phthalate (MEP).

The researchers generated z-scores for the analyte values to combine data across centers. Causal inference methods were applied to gauge the total effect of phthalates and hCG on AGD, which was then compared with the controlled direct effect of the phthalates after removing the hCG effect. 

High (90th percentile) vs. low (10th percentile) hCG was associated with 6% shorter AGD-AS in male and 6.8% longer AGD in female neonates (interaction of hCG by fetal sex, P = .02). Higher MnBP and MBzP were both associated with higher hCG expression in female neonates and lower expression in male (interaction P-value = .01). Neither AGD-AP nor AGD-AC correlated with first trimester placental hormones.

Male AGD decreased by 1.2 mm for every log-unit increase in urinary MEHP and MnBP. With hCG hypothetically blocked, MEHP and MnBP would induce 0.87-mm and 0.99-mm decreases, respectively, in AGD.

“There needs to be more research and more understanding at the population level about how these relationships work in the first trimester and how they relate to the outcomes in the babies at birth and beyond,” Adibi said. “Our data is showing that even though most of the literature and research has been focused on male development, phthalate exposure and placental hormones could be playing a role in female sex-specific development.” – by Allegra Tiver

Reference:

Adibi JJ. Abstract OR42-5. Presented at: The Endocrine Society Annual Meeting; March 5-8, 2015, San Diego. 

Disclosure: Adibi reports no relevant financial disclosures.

Editor's Note: On March 17, we corrected the first sentence in the ninth paragraph of this article to clarify study findings. The Editors regret this error.