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Mysteries and Controversies of the Placenta

Pregnancy bump with heart John HopeFor an organ the female body makes and then sheds all within less than a year, the placenta has long held a place of reverence in human culture. But for scientists, the placenta still holds some mysteries and now some scholarly controversy.

The organ, which supplies a developing baby oxygen and nutrients, has always been thought by physicians to be free of bacteria and to protect the fetus from infection. But that view was questioned when a prominent 2014 study claimed that the normal placenta harbors a microbiome -- communities of bacteria, viruses and other microscopic organisms -- all its own, and may even seed a newborn with its first population of helpful bacteria. The study garnered much attention in the press, with a New York Times headline, “Study Sees Bigger Role for Placenta in Newborns’ Health”

“Will this be a productive lead, or will it fizzle out? Time will tell us,” commented Martin J. Blaser, director of the human microbiome program at NYU Langone Medical Center, in the NYT article.

Indeed, it’s two years later, and the story has a new chapter. A recent study published in the Microbiome Journal by a Penn team of microbiologists and ob-gyn doctors disputes the purported existence of a unique placental microbiome.

“Our study is like a shot across the bow,” said senior author Frederic D. Bushman, PhD, chair of Microbiology, and co-principal investigator of the PennCHOP Microbiome Program. “We could not find any evidence of a unique placental microbiome. Data like these are important to share, so the research community can wrestle with the implications and work toward a consensus.”

Bacterial infection of the placenta is thought to be involved in pregnancy complications, but the suggestion of a unique resident microbiome associated with healthy placenta was novel.

“A challenge in working with specimens with low levels of bacterial DNA, such as in placental samples, is that some or all of the bacterial DNA detected in sequencing data may come from background DNA in the air or commercial reagents used in experimental procedures,” Bushman said.

To get a better handle on the existence of a unique, resident placental microbiome, the team compared bacterial DNA from placental samples from six women who had healthy deliveries to a matched set of controls, as well as to oral and vaginal samples from the same women. Multiple types of “negative control” samples were collected as standards for comparing background DNA measurements to that in samples from the placentas. These control samples involved reagents used to purify DNA and materials normally used in placental sample preparation.

“We could not distinguish a difference between bacterial DNA in placental samples and the background control samples,” said co-senior author Samuel Parry, MD, chief of the Division of Maternal-Fetal Medicine. However, oral and vaginal samples did show characteristic, distinctive microbial composition as measured by their DNA sequences and as expected from many previous studies.

For this study, Parry, who researches ways to prevent preterm birth, looked to Bushman for data on placentas from normal births and lab controls as a baseline. Next, Parry plans to study placentas and bacteria from more than 500 women who deliver their babies early.

In light of the team’s latest findings, a group of five March of Dimes Centers of Research on preterm birth, including one at Penn, is setting up new studies to examine placental bacterial colonization in healthy and diseased placentas, if they exist, and to investigate how those finding might play a role in decreasing the number of babies born too soon.

In fact, studying placental dysfunction is one of the Penn center’s three main areas of investigation. They are working on identifying changes in the mitochondria, metabolic patterns, epigenetics, and the microbiome that may cause placental dysfunction, and ultimately lead to preterm birth. The center complements Penn Medicine’s Prematurity Prevention Program, which aims to identify women at risk for premature labor and/or delivery.

All of these efforts are banking on discovering more knowledge about a little studied, ephemeral organ essential to helping moms deliver healthy babies.

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