Short communicationRestriction of placental vasculature in a non-human primate: A unique model to study placental plasticity
Introduction
Animal models of placental compromise have focused on fetal outcomes [1], [2], [3], while placental adaptations have been largely overlooked. Furthermore, interspecies differences in placental structure [4] and methodology to mimic vascular insufficiency (e.g., embolization [5] or carunclectomy [6]), limit the translational value of some animal models for human research. The hemochorial placenta of the rhesus monkey is similar to human, but is distinguished by two lobes [7]. The umbilical cord attaches centrally to a primary lobe (approximately 60% of the functional placental unit) and clusters of bridging vessels supply a structurally independent secondary lobe. The bi-lobed placenta can be exploited to provide a non-human primate (NHP) model of placental compromise by ligating the feto-placental blood vessels that bridge the primary and secondary placentas, so called inter-placental bridging vessel ligation (IPVL). Myers and co-workers reported IPVL at 98–102 days gestation (dGA) in the NHP results in asymmetrical fetal growth restriction (FGR) [8]. In contrast, Novy et al. reported that earlier IPVL at 80–90 dGA resulted in compensatory placental growth (increased DNA content) with an absence of FGR [9]. These observations suggest there may be a critical window for placental plasticity near mid-gestation which may compensate for relative utero-placental insufficiency and allow normal fetal growth. However, the impact of placental circulatory and metabolic adaptations on fetal development and the long-term consequences of fetal programming on adult onset disease remain to be elucidated [10], [11]. This model was originally developed prior to the knowledge of developmental programming, and before the availability of non-invasive vascular imaging techniques. Therefore, we have re-established this NHP model utilizing IPVL at two distinct gestational ages (80 and 110 days) followed by concurrent longitudinal ultrasound studies of maternal utero-placental and fetal hemodynamic adaptations. We report our methods and initial results to highlight the feasibility of this novel animal model and to suggest avenues for future research on the mechanisms which mediate adaptations to in utero vascular insults.
Section snippets
Methods
This protocol was approved by the Institutional Animal Care and Use Committee of the ONPRC, and humane animal care was followed. We performed inter-placental vessel ligation surgery at either early (80 dGA, n = 4) or late (110 dGA, n = 3) gestation [9]. Term gestation for the rhesus monkey is approximately 167 days. Hysterotomy was performed in the uterine fundus without exteriorization of the fetus. Amniotic fluid was aspirated and returned prior to uterine closure. Placental bridging vessels were
Results and discussion
The primary finding of this study is that inter-placental vessel ligation in the rhesus monkey results in a number of adaptive responses in the placenta, fetus and mother. Fetal growth tended to be diminished in the late group (312 ± 18 g body weight) compared to the early group (340 ± 12 g); predicted body weight for rhesus macaque fetuses at 140 dGA is 361 ± 49 g [8]. Compensatory changes in the primary (functional) placental lobe included an increase in mean weight (97 g vs. 71 g) and thickness (1.3 vs.
Funding support
K99 HD055059, 4R00 HD055053, RR00163, R01 HL087710.
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2022, American Journal of Obstetrics and GynecologyCitation Excerpt :Decreased placental perfusion and fetal oxygen availability occurred most significantly at middle to late gestation but was the lowest at G110, 50 days after ethanol cessation. Although early alcohol exposure seemed to impact fetal birthweight in a smaller subset of animals,23 in this larger cohort, preserved fetal growth and placental weight were observed, suggestive of the NHP placenta’s adaptive capabilities to early transient environmental perturbations19,50 compared with chronic prenatal insults throughout gestation.25,51,52 Despite this compensatory response, the reduced placental oxygenation at G135 combined with the presence of placental microinfarctions suggested a persistent placental injury that could further disrupt fetal development in ongoing pregnancies.
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Placental villous hypermaturation is associated with improved neonatal outcomes
2019, PlacentaCitation Excerpt :However, none of these effects were significant when adjusting for birthweight (data not shown). Clinically, accelerated maturation is viewed as a sign of utero-placental insufficiency and this interpretation is supported by experimental evidence from a non-human primate model [31]. The term “accelerated placental maturation” is used to describe a variety of related phenotypes, and in the present study we examined placental villous hypermaturation (PVH [18]) where a preterm placenta has the morphological appearance of a term placenta.