Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum.

Abstract

Rare nucleated fetal cells circulate within maternal blood. Noninvasive prenatal diagnosis by isolation and genetic analysis of these cells is currently being undertaken. We sought to determine if genetic evidence existed for persistent circulation of fetal cells from prior pregnancies. Venous blood samples were obtained from 32 pregnant women and 8 nonpregnant women who had given birth to males 6 months to 27 years earlier. Mononuclear cells were sorted by flow cytometry using antibodies to CD antigens 3, 4, 5, 19, 23, 34, and 38. DNA within sorted cells, amplified by PCR for Y chromosome sequences, was considered predictive of a male fetus or evidence of persistent male fetal cells. In the 32 pregnancies, male DNA was detected in 13 of 19 women carrying a male fetus. In 4 of 13 pregnancies with female fetuses, male DNA was also detected. All of the 4 women had prior pregnancies; 2 of the 4 had prior males and the other 2 had terminations of pregnancy. pearance. In a group of 20 primigravidas sampled on more than one occasion postpartum, quinacrine fluorescent signals ("Y body") were seen at a frequency of 0.01-0.1% of lymphocytes. These frequencies were noted to remain "practically unchanged" up until 1 year after delivery, when the study ended. In a related study, Ciaranfi et al. (5) (4) to include samples from women 5-7 years postpartum (5). In a series of 62 women who delivered a male infant, more than half had detectable male lymphocytes 2 years after birth. In some cases, metaphases with a Y chromosome were visualized 5 years postpartum. These studies, although intriguing, were performed in the 1970s using techniques less sensitive and less accurate than those available today.During this decade, investigators using PCR amplification of Y chromosome-specific sequences to identify fetal cells in maternal blood noted "false positive" results-i.e., detection of male DNA when the fetus was female (6, 7). Although laboratory contamination as a source of true false positives can be a concern (8), it appears that, in some cases, the male DNA was a real finding, possibly originating from a prior pregnancy (9). Other investigators studied postpartum maternal samples without using cell separation techniques to enrich for specific subpopulations of fetal cells and concluded that fetal cells did not persist postpartum (10).The study reported here occurred in two parts. Initially, we used a monoclonal antibody to cluster differentiation antigen (CD) 34 to isolate fetal hematopoietic stem cells from the blood of pregnant women. The surprising results, described below, suggested that the gender of the circulating CD34+ cells did not always correlate with the fetal gender of the current pregnancy. This led to the hypothesis that fetal CD34+ cells could persist from a prior pregnancy. We tested this hypothesis by fluorescence-activated cell sorting of four specific subpopulations of mononuclear cells from women who were not presently pregnant but who had previously given birth to a male infant. Although we were in...

Sex redefined

“…It was first identified in the early 1970s -but the big surprise came more than two decades later, when researchers discovered how long these crossover cells survive, even though they are foreign tissue that the body should, in theory, reject. A study in 1996 recorded women with fetal cells in their blood as many as 27 years after giving birth 13 ; another found that maternal cells remain in children up to adulthood 14 . This type of work has further blurred the sex divide, because it means that men often carry cells from their mothers, and women who have been pregnant with a male fetus can carry a smattering of its discarded cells.…”

The influence of fetal loss on the presence of fetal cell microchimerism: A systematic review

“…Most, if not all, pregnant women have fetal cells in their circulation (1). The persistence of these cells for decades after pregnancy has also been demonstrated (2). However, it remains unclear why fetal cells persist in some women, creating a microchimeric state, and not in others.…”

Pregnancy and microchimerism in autoimmune disease: Protector or insurgent?

“…Although male DNA was used as the measure of microchimerism, women with SSc who had sons were studied for T lymphocyte microchimerism without comparison with control women with sons. The absence of appropriate controls was notable in view of the earlier description by Bianchi et al of fetal microchimerism among T lymphocytes in healthy women (2). Subsequent studies confirmed that simple detection of fetal microchimerism is common among T lymphocytes (and also in monocytes, natural killer cells, and B cells) in both women with SSc and healthy women (13).…”