FOR: The placenta is the villain in the pathogenesis of
preeclampsia.
Padma Murthi1-3 and Shaun P
Brennecke2,3
1Department of Pharmacology, Monash Biomedicine
Discovery Institute, Monash University, Clayton, Victoria, Australia.
2Department of Obstetrics and Gynaecology, University
of Melbourne, Parkville, Victoria, Australia.
3Department of Maternal-Fetal Medicine, Pregnancy
Research Centre, Royal Women’s Hospital, Parkville, Victoria, Australia.
In keeping with legal precedent when prosecuting a case, quoting a pithy
Latin phrase can often be a winning gambit.
Simply put, therefore, in arraigning the placenta as culpable in the
pathogenesis of preeclampsia, sine qua non surely does the trick,
for without a placenta, there is no preeclampsia. While a fetus or a
gravid uterus is usually sufficient for an occurrence of preeclampsia,
neither is in fact necessary. Exhibit one, a hydatidiform mole, bears
witness to the former contention, and exhibit two, an abdominal
pregnancy, to the latter (Redman. N Engl J Med 1990; 323: 478 –
480). It is the placenta that is caught red-handed as the culprit.
Moreover, notwithstanding the continuing validity of Paul Zweifel’s
pronouncement in 1916 (Zweifel, P. Eklampsie. In: Dederlein, A.,
editor. Handbuch Der Geburtshilfe. Bergman: Wiesbade: 1916. p. 672 –
723) that (pre-) eclampsia is a disease of theories, the overwhelming
weight of contemporary research evidence firmly places the placenta
front and centre at the scene of the crime (Burton et al. BMJ 2019; 366:12381.1-15).
While other bodily organs and systems (including renal, hepatic,
cerebral, cardiovascular, haematological) may be complicit in the
grievous bodily harm (GBH) wreaked upon a pregnancy by preeclampsia, the
placenta cannot use their downstream dysfunctions as conviction-avoiding
alibis. The placenta is undoubtedly the ringleader and puppet-master of
the gang. Modern detective work has shown the placenta exercises its
sinister influence by using a large arsenal of weapons (including
anti-angiogenic molecules, pro-inflammatory cytokines, and a wide array
of necrotic and apoptotic trophoblast microvesicles). Once in
circulation, this ordnance attacks the innocent and unsuspecting, occasioning the GBH which is the criminal subject of this prosecution
(Burton et al. BMJ 2019; 366:12381.1-15).
Now it may be proposed that this trophoblastic villainy is to be excused
because the placenta at a very young and tender stage of its development
may be subject to deleterious, stress-inducing influences (probably
parentally immunogenetic in origin). This in turn causes histological
and cytological maldevelopment of the placenta which leads to its
subsequent malevolent misbehaviour as pregnancy progresses, resulting in
preeclampsia (in particular, the early onset type) (Brosens et al. Am J Obstet Gynecol 2019; 221(5): 437-456; Huppertz Hypertension 2008; 51(4): 970-975). Thus the impact of the
placenta under this scenario is predetermined and not primarily of its
own making. However, this line of argument cannot be allowed to absolve
the placenta of ultimate responsibility for the pathogenesis of
preeclampsia. This is because in the so called late onset type of
preeclampsia (which is the majority of cases), evidence of early
pregnancy insult is less discernible, with placental culpability being
more associated with (premature) senescence of the mature placenta
(Staff. J Reprod Immunol 2019; 134-135:1-10).
Before closing the case for the prosecution, witness impact statements
relating to the world-wide and life-long harm associated with
preeclampsia should be highlighted
(Duley. Semin Perinatol. 2009; 33(3):130-137; Leslie and Briggs. J Midwifery Women’s Health 2016; 61(3): 315-324).
Therefore, any placenta found guilty as charged in a case of
preeclampsia should be sentenced upon conviction to be dissected and
then to spend as much time as ethically permitted housed in a secure
biobank. This may allow eventual redemption in the form of revelations
following further interrogation that clarify precisely the placental
aetiology of preeclampsia at long last.
Disclosure of interests
No conflicts to declare.
.