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Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
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Listeria may be a serious miscarriage threat

Listeria is a common food-borne bacterium that may be a greater risk for miscarriage in early pregnancy than thought.

According to researchers at the University of Wisconsin-Madison (UW-Madison) School of Veterinary Medicine who study how pathogens affect fetal development, the bacterium affects those with stressed immune systems and can change the outcome of pregnancy.

"For many years, listeria has been associated with adverse outcomes in pregnancy, but particularly at the end of pregnancy,"
says Ted Golos, a UW-Madison reproductive physiologist and professor of comparative biosciences and obstetrics and gynecology. "What wasn't known with much clarity before this study, is that it appears it's a severe risk factor in early pregnancy."

Golos and his collaborators published their results Feb. 21, 2017 in the journal mBio.

According to the Centers for Disease Control, listeria makes about 1,600 Americans sick each year, a fairly small number, but higher in newborn babies and older adults with undeveloped or weak immune systems.

"The problem with this organism is not a huge number of cases. It's that when it is identified, it's associated with severe outcomes," says Charles Czuprynski, a UW-Madison professor of pathobiological sciences and director of the UW-Madison Food Research Institute.

Pregnant women are warned to avoid many of the foods — among them unpasteurized milk and soft cheese, raw sprouts, melon and deli meats not carefully handled — that can harbor listeria, as the bacterium is known to cause miscarriage and stillbirth, and premature labor. These severe outcomes demand a zero-tolerance regulatory policy for listeria in ready-to-eat foods.

When it occurs, listeria infection in pregnancy may go unnoticed. The few recognizable symptoms are nearly indistinguishable from the discomfort most newly pregnant women feel.

"It's striking that mom doesn't get particularly ill from listeria infection, but it has a profound impact on her fetus," says Golos, whose work is funded by the National Institutes of Health. "That's familiar now, because we've been talking about the same difference in Zika virus."

Sophia Kathariou, a North Carolina State University professor of food science and microbiology, provided a strain of listeria found to have caused miscarriage, stillbirth and premature delivery in at least 11 pregnant women in 2000. Four pregnant rhesus macaques at the Wisconsin National Primate Research Center were fed doses of the listeria comparable to what one might encounter in contaminated food. Bryce Wolfe, a UW-Madison graduate student studying cellular and molecular pathology who is lead author of the study, monitored the speed and progression of listeria's spread.

"What's particularly striking about the work is the detailed information we now have about the organism. After the animals ingested it, Bryce tracked it being shed in feces and how it showed up in the bloodstream. The ultrasound analysis of the fetus, then show events in terms of where the organism was preceding fetal demise."

Charles J. Czuprynski PhD, Department of Pathobiological Sciences, University of Wisconsin-Madison, Wisconsin, USA

None of the monkeys showed obvious signs of infection before their pregnancies came to abrupt ends. But in tissue samples taken after each monkey experienced intrauterine fetal death, Wolfe found listeria had invaded the placenta — the connection between the mother-to-be and the fetus, which usually prevents transmission of bacteria — as well as the endometrium, the lining of the uterus.

"In that region, there's a rich population of specialized immune cells, and it is exquisitely regulated," says Wolfe. "When you introduce a pathogen into the midst of this, it's not very surprising that it's going to cause some sort of adverse outcome disrupting this balance."

Researchers believe an inflammatory response by the maternal immune systen to the fast-moving listeria keeps the placenta from protecting the fetus.

"It should be a barrier," Golos says. "But we hypothesize that the maternal immune system's attempt to clear the bacteria actually results in collateral damage to the placenta, which allows the bacteria to invade the fetus."

The results suggest listeria (and perhaps other pathogens) may be the culprit in some miscarriages that usually go without diagnosed cause, but the bacteria's stealth and speed may still make it hard to control.

"There are effective antibiotics available as it is treatable. However, because it's asymptomatic, the fetus may be infected by the time anyone realizes the mother is infected."

Bryce Wolfe, graduate student, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Wisconsin, USA

Golos and Wolfe plan to continue work with listeria to better define how the bacterium targets the reproductive tract, its incubation time and the problems it causes leading up to miscarriage. Their goal is to provide basic knowledge about the progression of infection and the maternal immune response to intracellular pathogens in pregnancy, which may help other researchers battling similar dangers such as Zika virus.

Although listeriosis is known to cause significant fetal morbidity and mortality, it is typically recognized in the third trimester of human pregnancy. Its impact on early pregnancy is poorly defined. Here we provide evidence that exposure to L. monocytogenes in the first trimester poses a greater risk of fetal loss than currently appreciated. Similarities in human and nonhuman primate placentation, physiology, and reproductive immunology make this work highly relevant to human pregnancy. We highlight the concept that the maternal immune response that protects the mother from serious disease is unable to protect the fetus, a concept relevant to classic TORCH (toxoplasmosis, other, rubella, cytomegalovirus, and herpes) infections and newly illuminated by current Zika virus outbreaks. Studies with this model, using the well-understood organism L. monocytogenes, will permit precise analysis of host-pathogen interactions at the maternal-fetal interface and have broad significance to both recognized and emerging infections in the setting of pregnancy.

Authors: Bryce Wolfea,b, Gregory J. Wiepza,c, Michele Schotzkoa, Gennadiy I. Bondarenkoa, Maureen Durninga, Heather A. Simmonsa, Andres Mejiaa, Nancy G. Faithd, Emmanuel Sampenee, Marulasiddappa Sureshd, Sophia Katharioug, Charles J. Czuprynskid, Thaddeus G. Golosa

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
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An electron microscope image of the bacteria: Listeria Monocytogenes.
Image Credit: CDC/James Archer

Phospholid by Wikipedia