Paternal Determinants in Preeclampsia

Abstract

Preeclampsia is a condition associated with high rates of maternal-fetal morbidity and mortality. It usually occurs in 3–10% of nulliparous women and 18% of previously affected women. Different lines of evidence have demonstrated the role of the father in the onset of preeclampsia. The placenta is the cornerstone of preeclampsia and poses important paternal genetic determinants; in fact, the existence of a “paternal antigen” has been proposed. Nulliparity is a well-known risk factor. Change of partner to a woman without history of preeclampsia increases the risk; however, this change decreases in women with history of the condition. High interval between pregnancies, short sexual intercourse before pregnancy, and conception by intracytoplasmic sperm injection suggest a limited exposure to the so-called paternal antigen. A man who was born from a mother with preeclampsia also increases the risk to his partner. Not only maternal but also paternal obesity is a risk factor for preeclampsia. Fetal HLA-G variants from the father increased the immune incompatibility with the mother and are also significantly associated with preeclampsia in multigravida pregnancies. An analysis of a group of Swedish pregnant women showed that the risk for preeclampsia is attributable to paternal factors in 13% of cases, which could be related to genetic interactions with maternal genetic factors. This review aimed to evaluate the evidences of the father’s contribution to the onset of preeclampsia and determine the importance of including them in future studies.

Prevalence and determinants of hypertensive disorders of pregnancy in Ethiopia: A systematic review and meta-analysis

“…Researchers identified different risk factors for HDP [ 9 , 10 ]. Factors like; advanced maternal age, twin pregnancy, being primigravida, previous history of preeclampsia, family history of hypertension (HTN), family history of diabetes mellitus (DM) [ 11 ], being overweight or obesity or body mass index (BMI) ≥25 [ 9 , 11 ], urinary tract infection (UTI) [ 12 ], alcohol consumption [ 13 ], lack of fruits and vegetables [ 14 ] during pregnancy increase the risk of HDP.…”

Research Article Association of HLA-G 14-base pair insertion/deletion polymorphism with breast cancer in Saudi Arabia

“…Approximately 50 polymorphic sites have been mapped either in non-coding or coding regions (IMGT HLA database, December 2013). The HLA-G molecule was reported for its tolerogenic function mainly in the maternal-fetal interface, helping to protect the fetus from destruction by the mother's immune defense system (Kovats et al, 1990;Menter and Tzankov, 2018;Galaviz-Hernandez et al, 2019). Considering the tolerogenic properties of the HLA-G molecule, many studies have detected an association between the aberrant expression of HLA-G and the occurrence of several types of malignancies such as colorectal cancer, esophageal cancer, uterine cervical cancer, ovarian carcinoma, hepatocellular carcinoma, carcinoma of bladder, and breast cancer (Rouas-Freiss et al, 2005a;Zidi and Ben Amor, 2011;Kim et al, 2013;Rolfsen et al, 2014;Rutten et al, 2014;Zhang and Tao Wang, 2014;Zidi et al, 2016;Zambra et al, 2016;de Almeida et al, 2018;Lin and Yan, 2018) as well as several other diseases such as infections, autoimmunity, and abortion (Donadi et al, 2011;Vargas et al, 2011;Garcia et al, 2013;Dias et al, 2015;Sabbagh et al, 2018;).…”

Preeclampsia Is a Syndrome with a Cascade of Pathophysiologic Events

“…First-degree relatives of affected individuals have a 3–5-fold increased risk of PE [ 8 ]. Pregnancies fathered by partners who themselves were born after PE are twice as likely to develop PE, and men who have already conceived a preeclamptic pregnancy are at greater risk of recurrent PE in subsequent pregnancies [ 8 , 9 ]. In mono- and dizygotic female twin pairs, PE heritability is estimated to be 54%.…”

“…Primigravid women show a three-fold higher rate of PE than multigravida women, and those who have had limited reproductive contact with paternal antigens in the preconception period are at particular risk. This circumstance can arise from a short prepregnancy period of cohabitation, the use of a barrier method of contraception, a new partnership, azoospermia treated with surgical sperm extraction before intracytoplasmic sperm injection (ICSI), or donor insemination [ 6 , 9 ]. These observations strongly suggest that the maternal immune system plays an important role in the etiology of PE, as will be discussed further in the section on the immune system, implantation, and vascular remodeling.…”

“…Another important group of predisposing factors for PE are individual characteristics, such as body mass index (BMI) > 25 kg/m 2 , age > 35 years, school education ≤ 10 years, grand multiparity (≥5), and a history of PE, abruption, or stillbirth [ 14 ]. A predisposition to gestation-specific PE is also observed in multiple pregnancies [ 14 ], and after conception with artificial reproductive treatments, particularly in vitro fertilization and ICSI techniques [ 15 ], irrespective of whether the gametes are from partners or donors or whether it is a singleton or multiple pregnancy [ 9 , 14 , 16 , 17 ].…”