*2.2.2 Failure of step 2: failed trophoblastic migration*

An impaired rise in blood flow, as a result of improper decidualization and improper angiogenesis, leads to a failed integrin shift and a failure of trophoblast to acquire an endothelial phenotype. Disturbed HLA-G expression by trophoblast has also been postulated. This might explain preeclampsia seen in association with molar pregnancy.

#### *2.2.3 Failure of step 3: trophoblast-associated remodeling is defective*

Impaired intramural incorporation of endovascular trophoblast and lack of fibrin deposition can be caused by impaired secretion of proteinases. This may be because of improper trophoblast signaling. This might explain the increased risk preeclampsia in connective tissue disorders, SLE, and APLA. The defective laying down of fibrin may explain the preeclampsia in cases of thrombophilia disorders like factor 2 and factor 5 Leiden mutations, serpin gene mutations,

**11**

*Introductory Chapter: The Multiple Etiologies of Preeclampsia*

*2.2.4 Failure of step 4: increased maternal inflammatory response*

and protein C and protein S deficiencies. This might also explain the association of preeclampsia with placenta accreta and increta where the Nitabuch's layer is absent. Chronic hypertension, renal disease, increased maternal age, and diabetes may lead to hyperplasia of smooth muscles of spiral arterial media; this may lead to impaired maintenance of elastin and vascular smooth muscles [14, 15]. When these conditions are present subclinically before pregnancy, the preexisting Tunica media hyperplasia might interfere with trophoblast-induced apoptosis

Trophoblast proliferation and apoptosis of maternal intra-arterial smooth muscles invariable incites maternal tissue repair mechanisms, it is easy to understand that if maternal inflammation is marked the proliferating trophoblast may be destroyed by lipophages resulting in "acute atherosis lesions" in the placental bed [16]. This might explain the occurrence of preeclampsia in Rh-incompatible pregnancies and

Syncytial sprouts arise from the syncytiotrophoblast that covers the cytotrophoblast around the fetal stem villi. In early pregnancy large aggregates of trophoblastic cells proliferate and extend into the intervillous space forming drumstick-like syncytial structures. Syncytial sprouts are multinucleated and have large ovoid nuclei with very little heterochromatin. There are a large number of ribosomes with abundant rough endoplasmic reticulum. Larger nuclei are present in the sprouts as compared to other parts of syncytiotrophoblast. True sprouts are produced from the mesenchyme villi and immature intermediate villi (**Figure 5**). There are continuous differentiation and proliferation of cytotrophoblast into syncytiotrophoblast into sprouts. This can be (a) sprout-like apoptotic shedding, (b) knots or Tenny-Parker changes, (c) wavelike apoptotic shedding, (d) arrested apoptotic shedding,

This is a normal phenomenon in which villous trophoblast proliferates and differentiates into cytotrophoblast. The cytotrophoblast fuses with the overlying syncytiotrophoblast, and finally the old and aging material is packaged into apoptotic syncytial sprouts and released into the maternal circulation. If apoptotic shedding is blocked, the number of nuclei in the syncytium increases. Since it is a membrane-sealed apoptotic material, it does not induce an inflammatory response. In the maternal lung, the syncytial sprouts get trapped and are phagocytosized by lung macrophages without inflammatory reaction. Approximately 3 g of apoptotically shed trophoblast is destroyed in the lungs daily. This is the balance of 3.6 g of cytotrophoblast that is converted to syncytiotrophoblast each day and 0.6 g that is retained in the syncytium [17, 18].

The terms syncytial sprouts and syncytial knots are different. True syncytial sprouts happen in first half of pregnancy when they represent early stages of large euchromatic nucleus. Tenny-Parker changes also called as syncytial knots are

*DOI: http://dx.doi.org/10.5772/intechopen.86177*

of elastic smooth muscles.

hyperhomocysteinemia (**Table 1**).

**3. The fetal side of fetoplacental interface**

(e) aponecrotic shedding, and (e) necrotic shedding.

**3.2 Tenny-Parker changes or syncytial knots**

**3.1 Sprout-like apoptotic shedding**

*Introductory Chapter: The Multiple Etiologies of Preeclampsia DOI: http://dx.doi.org/10.5772/intechopen.86177*

*Prediction of Maternal and Fetal Syndrome of Preeclampsia*

study demonstrated that even decidual segments might show incomplete remodeling. It is imperative that the placental bed biopsy should be taken from an adequately central space and not lateral. There are less interstitial giant cells in the myometrium and more stacked endometrial glands pushed by the placenta at the periphery of the

**High risk Possible explanation Prediction by Clinical features**

Central venous pressure and pulmonary capillary wedge pressures, colloid osmotic pressure, pulmonary crept, clinical congestive heart failure, cerebral edema

Postpartum convulsions due to posterior reversible encephalopathy syndrome vasogenic edema in posterior brain due to lack of sympathetic modulation

Factors affecting increased urinary sodium excretion between 3 and 5 days after birth (increase of atrial natriuretic peptide in the first week after delivery, natriuresis and inhibition of aldosterone, angiotensin II, vasopressin)

Late luteal phase secretory endometrium decidualization is associated with infiltration of natural killer cells, which are now considered to be major effector cells at trophoblast-uterine interphase interactions. It has also been postulated that repeated cycles of menstrual shedding of decidualizing endometrium may act as preconditioning for successful implantation and deep placentation [13]. This might explain the increased risk of preeclampsia in teenage pregnancy, short interval of pregnancy since menarche, and primipaternity. This may also explain the lowered risk of preeclampsia in women who have intercourse earlier with partner who fathers the current pregnancy. Recent research also suggests that natural killer cells' associated defects of implantation are due to disturbed ligand receptor interphase. Uterine natural killer cells are absent in the JZ myometrium, but their angiogenic action is mediated by interstitial trophoblast.

An impaired rise in blood flow, as a result of improper decidualization and improper angiogenesis, leads to a failed integrin shift and a failure of trophoblast to acquire an endothelial phenotype. Disturbed HLA-G expression by trophoblast has also been postulated. This might explain preeclampsia seen in association with

Impaired intramural incorporation of endovascular trophoblast and lack of fibrin deposition can be caused by impaired secretion of proteinases. This may be because of improper trophoblast signaling. This might explain the increased risk preeclampsia in connective tissue disorders, SLE, and APLA. The defective laying down of fibrin may explain the preeclampsia in cases of thrombophilia disorders like factor 2 and factor 5 Leiden mutations, serpin gene mutations,

*2.2.1 Failure of step 1: decidua-associated remodeling is defective*

*2.2.2 Failure of step 2: failed trophoblastic migration*

*2.2.3 Failure of step 3: trophoblast-associated remodeling is defective*

**10**

molar pregnancy.

placental bed.

pregnancy)

**Table 1.**

**2.2 Failure of remodeling**

*Possible prediction of various subtypes of preeclampsia.*

Postpartum preeclampsia, inadequate mobilization of liquid from the interstitial and intravascular to extravascular space (6–8 L of the total body water, return of 950 mEq of total body sodium accumulated during

and protein C and protein S deficiencies. This might also explain the association of preeclampsia with placenta accreta and increta where the Nitabuch's layer is absent. Chronic hypertension, renal disease, increased maternal age, and diabetes may lead to hyperplasia of smooth muscles of spiral arterial media; this may lead to impaired maintenance of elastin and vascular smooth muscles [14, 15]. When these conditions are present subclinically before pregnancy, the preexisting Tunica media hyperplasia might interfere with trophoblast-induced apoptosis of elastic smooth muscles.

#### *2.2.4 Failure of step 4: increased maternal inflammatory response*

Trophoblast proliferation and apoptosis of maternal intra-arterial smooth muscles invariable incites maternal tissue repair mechanisms, it is easy to understand that if maternal inflammation is marked the proliferating trophoblast may be destroyed by lipophages resulting in "acute atherosis lesions" in the placental bed [16]. This might explain the occurrence of preeclampsia in Rh-incompatible pregnancies and hyperhomocysteinemia (**Table 1**).
