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Inhibition of activin A signalling in a mouse model of pre-eclampsia

Lim R, Adhikari S, Gurusinghe S, Leaw B, Acharya R, Rahman R, et al.

Placenta, 2015 Aug;36(8):926-31.
PMID: 26138362 DOI: 10.1016/j.placenta.2015.06.004

Pre-eclampsia remains a major cause of maternal and fetal morbidity and mortality. Despite intensive research over the last 50 years, significant therapeutic advances have yet to be realised. We recently reported on the role of activin A in the pathophysiology of pre-eclampsia, whereby a pre-eclampsia-like disease state was induced in pregnant mice through activin A infusion. Using the same animal model, the effects of inhibiting activin A signalling on this pre-eclampsia-like disease state have now been assessed with low molecular weight compounds structurally related to activin-receptor-like kinase (ALK) inhibitors.
Raised prorenin and renin concentrations in pre-eclamptic placentae when measured after acid activation

Singh HJ, Rahman A, Larmie ET, Nila A

Placenta, 2004 Aug;25(7):631-6.
PMID: 15193869

The aim of the study was to ascertain if there was any difference in the levels of prorenin and active renin between pre-eclamptic and normotensive feto-placental tissues.

Matched MeSH terms: Placenta/chemistry*
Charlie Loke: contributions from Tennis Court Road--past, present and future

Moffett A

Placenta, 2003 Apr;24 Suppl A:S4-9.
PMID: 12842407
Weight, volume and surface area of placenta of normal pregnant women and their relation to maternal and neonatal parameters in Malay, Chinese and Indian ethnic groups

Sivarao S, Vidyadaran MK, Jammal AB, Zainab S, Goh YM, Ramesh KN

Placenta, 2002 10 4;23(8-9):691-6.
PMID: 12361688

This study was conducted to determine the effect of ethnicity on maternal, placental and neonatal parameters. Maternal, placental, and the newborn parameters were corrected for gestational age. The male:female sex ratio was 1:1.03. One hundred and forty-four freshly delivered placentae from 55 Malaysian, 51 Chinese, and 38 Indian normal healthy patients were collected and standard stereological methods used to estimate the placental parameters. Pearson's correlation, Spearman's correlation and 1-way ANOVA were used to test significance of differences. Placental surface area, placental weight and placental volume of Indians were lower than Malays (P< 0.05). Placental weight correlated significantly with neonatal length (r=0.527), birthweight (r=0.665), head circumference (r=0.371) and booking weight (r=0.193) while placental volume correlated with neonatal length (r=0.588), birthweight (r=0.688), head circumference (r=0.384), parity (r=0.202) and booking weight (r=0.219) at P< 0.05. Indian babies weight and length were less than Chinese and Malay babies (P< 0.05) while booking weight of Indian mothers was less than those of Chinese mothers (P< 0.05). Even after being corrected for booking weight, placental parameters of Indian patients were still significantly less than Malays and Chinese (P< 0.05).

Matched MeSH terms: Placenta/anatomy & histology*; Placenta/physiology
Notes on placentation in the Suina

Macdonald AA, Bosma AA

Placenta, 1985 1 1;6(1):83-91.
PMID: 3991477

We examined the gross and microscopic anatomy of placental tissues and umbilical cords from six species representing the three living families of the Suina. These species included, of the Suidae, the wart hog (Phacochoerus aethiopicus), the giant forest hog (Hylochoerus meinertzhageni), the domestic pig (Sus scrofa), and the banded pig of Malaysia (Sus scrofa vittatus); of the Tayassuidae, the white-lipped peccary (Tayassu pecari); of the Hippopotamidae, the hippopotamus (Hippopotamus amphibius) and the pigmy hippopotamus (Choeropsis liberiensis). All these species have a diffuse epitheliochorial placenta. The chorion is folded, and has on its surface rows of shallow ripples or villi, interrupted by round, oval or irregularly shaped areolae. Placental capillaries indent the epithelial layer covering the tops and sides of the interareolar villi, but not the columnar cell layer lying in the troughs between these villi or covering the areolae. Cuboidal cells cover the crests of the villi in the Suidae and Hippopotamidae, whereas in the Tayassuidae the epithelium is syncytial in appearance. The similarities in placental structure between the six species are more apparent than the differences. Suidae and Tayassuidae have smooth umbilical cords containing two arteries and one vein; those of the Hippopotamidae are pustule-encrusted and contain two arteries and two veins.

Matched MeSH terms: Placenta/anatomy & histology*; Placenta/ultrastructure
Fulltext Activin A and pathologies of pregnancy: a review

Barber CV, Yo JH, Rahman RA, Wallace EM, Palmer KR, Marshall SA

Placenta, 2023 May;136:35-41.
PMID: 37028223 DOI: 10.1016/j.placenta.2023.03.008

Activin A is a two-subunit protein belonging to the transforming growth factor β superfamily. First discovered almost three decades ago, it has since been implicated in diverse physiological roles, ranging from wound repair to reproduction. After 30 years of research, altered activin A levels are now understood to be associated with the development of various diseases, making activin A a potential therapeutic target. In pregnancy, the placenta and fetal membranes are major producers of activin A, with significantly enhanced serum concentrations now recognised as a contributor to numerous gestational disorders. Evidence now suggests that circulating levels of activin A may be clinically relevant in the early detection of pregnancy complications, including miscarriage and preeclampsia. This review aims to summarise our current understanding of activin A as a potential diagnostic marker in common pregnancy pathologies.
Non-hypertensive gestational diabetes mellitus: Placental histomorphology and its association with perinatal outcomes

Lai YM, Tan GC, Shah SA, Abd Rahman R, Mohd Saleh MF, Mansor S, et al.

Placenta, 2024 Mar 06;147:21-27.
PMID: 38278001 DOI: 10.1016/j.placenta.2024.01.012

INTRODUCTION: Gestational diabetes mellitus (GDM) exerts a great impact on the placenta and reflects changes on placentas both morphological and functionally. The aims of this study are to evaluate the prevalence of placental histopathological lesions in pregnancies complicated by GDM compared to gestational age-matched controls, and their association with maternal and fetal complications.
METHODS: Fifty-four singleton GDM-complicated pregnancies were recruited and compared to 33 consecutive normal pregnancies. Two pathologists, blinded to all clinical data, reviewed and evaluated all histological samples of the placentas in accordance with Amsterdam criteria. Relevant demographic, clinical data and primary birth outcomes were recorded.
RESULTS: A myriad of histomorphological abnormalities, including chronic inflammation (n = 9/54, p = 0.031), histological chorioamnionitis (n = 23/54, p placentas compared to the controls. Additionally, GDM significantly increased the risk of fetal complications, including macrosomia/fetal growth restriction (n = 13/54, p = 0.004).
DISCUSSION: Histoarchitectural abnormalities were observed more frequently in placentas of GDM pregnancies compared to the controls. Our findings support the hypothesis that diabetic-induced damage in the placental function may be associated with the increased in fetal growth disorders in GDM-complicated pregnancies.
Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction - A prospective study

Hong J, Crawford K, Daly M, Clifton V, da Silva Costa F, Perkins AV, et al.

Placenta, 2024 Aug 30;156:20-29.
PMID: 39232442 DOI: 10.1016/j.placenta.2024.08.016

INTRODUCTION: The aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality.
METHODS: This was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified.
RESULTS: There were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively).
CONCLUSION: MVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.