The trophoblast plug during early pregnancy: a deeper insight

Abstract

During the first trimester of pregnancy, foetal endovascular trophoblasts invade into maternal spiral arteries, accumulate and form plugs in the lumen of the vessels. These plugs only allow blood plasma to seep through. Hence, during the first trimester of pregnancy, a first flow of fluids through the placental intervillous space is established, resulting in a physiological oxygen gradient between mother and foetus. The trophoblast plugs block spiral arteries until the beginning of the second trimester (11–14 weeks). In parallel, uterine glands are invaded and opened by endoglandular trophoblasts towards the intervillous space of the placenta, without showing the formation of plugs (Moser et al. in Hum Reprod 25:1127–1136, 2010, Hum Reprod Oxf Engl 30:2747–2757, 2015). This enables histiotrophic nutrition of the embryo prior to onset of maternal blood flow into the placenta. Failure of these endovascular and endoglandular invasion processes may lead to miscarriage or pregnancy disorders such as intrauterine growth restriction (IUGR). After dissolution of the plugs, the onset of maternal blood flow allows maternal blood cells to enter the intervillous space and oxygen concentrations rise up. In this study, we demonstrate for the first time serial cross sections through a trophoblast plug in a first trimester placental bed specimen. Invaded and plugged arteries as well as invaded uterine glands in week 11 of gestation are visualized with specific immunohistochemical double staining techniques. We show that spiral artery plugs appear throughout the placental invasion zone and illustrate erythrocytes stowed due to trophoblast plugs. In addition, we give evidence of the presence of MMP-1 in plugs of invaded spiral arteries. The results reveal a better understanding and a closer insight into the morphological appearance of trophoblast plugs and the consequences for placental and uterine blood flow.

Hypoxia regulates placental angiogenesis via alternatively activated macrophages

“…[38][39][40] Failure of this process may be associated with preeclampsia. 22,41 It is interesting to note that exposure of macrophages to severe hypoxia for 48 hours abolished Hif1a mRNA expression ( Figure 3).…”

“…19 Hofbauer cells are involved in placental vasculogenesis and angiogenesis by regulating endothelial cells. 22 Although resembling an ischemiareperfusion-type injury, this is a normal physiological event, yet its significance to placental development is not fully understood. 21 Early in the 2nd trimester, the plug dissolves and maternal blood flow is now able to enter the intervillous spaces, thereby increasing O 2 levels up to 8% O 2 (60 mm Hg).…”

“…21 Early in the 2nd trimester, the plug dissolves and maternal blood flow is now able to enter the intervillous spaces, thereby increasing O 2 levels up to 8% O 2 (60 mm Hg). 22 Although resembling an ischemiareperfusion-type injury, this is a normal physiological event, yet its significance to placental development is not fully understood.…”

Developmental onset of cardiovascular disease—Could the proof be in the placenta?

“…6,29 During the first trimester, spiral arterioles are luminally obstructed by trophoblastic plugs, which then loosen and permit maternal blood flow into the intervillous space during the second and third trimesters. 6,30 The venous system also undergoes enlargement in diameter, increased distensibility, and reduced elastin content which should enhance venous capacity. 27 The umbilical cord arises from embryonic cells and is the conduit between the fetus and placenta.…”

In focus in HCB: from cell biology to tissue structure and function

“…Ohlmann, Tamm and coworkers performed morphological and biochemical studies on embryonic and postnatal transgenic mice with ocular overexpression of transforming growth factor-β, documenting mesenchymal transdifferentiation of retinal pigment epithelial (RPE) cells, diminished RPE vascular endothelial growth factor production, consequent atrophy of the choriocapillaris, and photoreceptor apoptosis (Ohlmann et al 2016). Weiss, Huppertz, Moser and coworkers studied first trimester human placenta, analyzing trophoblast plugs in spiral arteries and uterine glands to further our understanding of the role of these phenomena for placental blood flow (Weiss et al 2016). Finally, Hartmann, Bergmann, Fietz and coworkers collected morphological, biochemical and functional evidence indicating that steroid synthesis via sulfatase pathway in Sertoli cells may contribute to paracrine and intracrine regulation in human testis (Hartmann et al 2016).…”