<i>PTX3</i> Genetic Variation and Dizygotic Twinning in The Gambia: Could Pleiotropy with Innate Immunity Explain Common Dizygotic Twinning in Africa?

Sirugo, Giorgio; Edwards, Digna R. Velez; Ryckman, Kelli K.; Bisseyé, Cyrille; White, Marquitta J.; Kebbeh, Bunja; Morris, Gerard A. J.; Adegbola, Richard A.; Tacconelli, Alessandra; Predazzi, Irene; Novelli, Giuseppe; Vannberg, Fredrik; Odunsi, Kunle; Page, Grier P.; Williams, Scott M.

doi:10.1111/j.1469-1809.2012.00723.x

Cited by 11 publications

(8 citation statements)

References 43 publications

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“…This should, at least in theory, cause a gradual genetic selection against twinning. Since this is not the case, there may be important health benefits associated with DZ twinning [1], as recently confirmed in the Gambia [35]. …”

Section: Discussionmentioning

confidence: 99%

A prospective study of twinning and perinatal mortality in urban Guinea-Bissau

Bjerregaard-Andersen

Lund

Jepsen

et al. 2012

BMC Pregnancy Childbirth

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BackgroundDespite twinning being common in Africa, few prospective twin studies have been conducted. We studied twinning rate, perinatal mortality and the clinical characteristics of newborn twins in urban Guinea-Bissau.MethodsThe study was conducted at the Bandim Health Project (BHP), a health and demographic surveillance site in Bissau, the capital of Guinea-Bissau. The cohort included all newborn twins delivered at the National Hospital Simão Mendes and in the BHP study area during the period September 2009 to August 2011 as well as singleton controls from the BHP study area. Data regarding obstetric history and pregnancy were collected at the hospital. Live children were examined clinically. For a subset of twin pairs zygosity was established by using genetic markers.ResultsOut of the 5262 births from mothers included in the BHP study area, 94 were twin births, i.e. a community twinning rate of 18/1000. The monozygotic rate was 3.4/1000. Perinatal mortality among twins vs. singletons was 218/1000 vs. 80/1000 (RR = 2.71, 95% CI: 1.93-3.80). Among the 13783 hospital births 388 were twin births (28/1000). The hospital perinatal twin mortality was 237/1000.Birth weight < 2000g (RR = 4.24, CI: 2.39-7.51) and caesarean section (RR = 1.78, CI: 1.06-2.99) were significant risk factors for perinatal twin mortality. Male sex (RR = 1.38, CI: 0.97-1.96), unawareness of twin pregnancy (RR = 1.64, CI: 0.97-2.78) and high blood pressure during pregnancy (RR = 1.77, CI: 0.88-3.57) were borderline non-significant. Sixty-five percent (245/375) of the mothers who delivered at the hospital were unaware of their twin pregnancy.ConclusionsTwins had a very high perinatal mortality, three-fold higher than singletons. A birth weight < 2000g was the strongest risk factor for perinatal death, and unrecognized twin pregnancy was common. Urgent interventions are needed to lower perinatal twin mortality in Guinea-Bissau.

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Section: Discussionmentioning

confidence: 99%

A prospective study of twinning and perinatal mortality in urban Guinea-Bissau

Bjerregaard-Andersen

Lund

Jepsen

et al. 2012

BMC Pregnancy Childbirth

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“…Recombinant PTX3 N-terminal domain, that forms tetramers and contains the HC-binding site, is sufficient to rescue the defective assembly of the cumulus matrix of PTX3-deficient cumuli (133). Interestingly, PTX3 genetic variants in humans have been associated with female fertility (98) and dizygotic twinning in Gambia (136).…”

Section: Role In Female Fertilitymentioning

confidence: 99%

PTX3, a Humoral Pattern Recognition Molecule, in Innate Immunity, Tissue Repair, and Cancer

Garlanda

Bottazzi

Magrini

et al. 2018

Physiological Reviews

160

179

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Innate immunity includes a cellular and a humoral arm. PTX3 is a fluid-phase pattern recognition molecule conserved in evolution which acts as a key component of humoral innate immunity in infections of fungal, bacterial, and viral origin. PTX3 binds conserved microbial structures and self-components under conditions of inflammation and activates effector functions (complement, phagocytosis). Moreover, it has a complex regulatory role in inflammation, such as ischemia/reperfusion injury and cancer-related inflammation, as well as in extracellular matrix organization and remodeling, with profound implications in physiology and pathology. Finally, PTX3 acts as an extrinsic oncosuppressor gene by taming tumor-promoting inflammation in murine and selected human tumors. Thus evidence suggests that PTX3 is a key homeostatic component at the crossroad of innate immunity, inflammation, tissue repair, and cancer. Dissecting the complexity of PTX3 pathophysiology and human genetics paves the way to diagnostic and therapeutic exploitation.

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“…The overexpression of LH receptor mRNA in granulosa cells and under-expression of GDF9 by the oocyte in PCOS follicles compared to normal follicles of the same size suggest a premature terminal differentiation ( 70 , 71 ) and closely resemble the conditions promoting polyovulation and dizygotic twinning in sheep ( 72 , 73 ). Noteworthy, a study on PTX3 single-nucleotide polymorphisms (SNPs) performed in Gambia, where the dizygotic twinning incidence is the highest worldwide ( 74 ), showed that a specific three SNP haplotype GAG (at positions rs2305619, rs3816527 and rs1840680) is more frequent in mothers of dizygotic twins compared to women without a history of twinning ( 75 ). In addition, in another study performed on Ghanaian women, the same haplotype positively correlates with the number of children given birth during the lifetime ( 76 ).…”

Section: Immune Cell-derived Ptx3 and Human Ovarian Disordersmentioning

confidence: 99%

The Influence of Pentraxin 3 on the Ovarian Function and Its Impact on Fertility

et al. 2018

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Follicular development is a highly coordinated process that in humans takes more than 6 months. Pituitary gonadotropins and a variety of locally produced growth factors and cytokines are involved in determining a precise sequence of changes in cell metabolism, proliferation, vascularization, and matrix remodeling in order to obtain a follicle with full ovulatory and steroidogenic capability. A low-grade inflammation can alter such processes leading to premature arrest of follicular growth and female reproductive failure. On the other hand, factors that are involved in inflammatory response as well as in innate immunity are physiologically upregulated in the follicle at the final stage of maturation and play an essential role in ovulation and fertilization. The generation of pentraxin 3 (PTX3) deficient mice provided the first evidence that this humoral pattern recognition molecule of the innate immunity has a non-redundant role in female fertility. The expression, localization, and molecular interactions of PTX3 in the periovulatory follicle have been extensively studied in the last 10 years. In this review, we summarize findings demonstrating that PTX3 is synthesized before ovulation by cells surrounding the oocyte and actively participates in the organization of the hyaluronan-rich provisional matrix required for successful fertilization. Data in humans tend to confirm these findings, indicating PTX3 as a biomarker of oocyte quality. Moreover, we discuss the emerging evidence that in humans altered PTX3 systemic levels, determined by genetic variations and/or low-grade chronic inflammation, can also impact the growth and development of the follicle and affect the incidence of ovarian disorders.

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PTX3 Genetic Variation and Dizygotic Twinning in The Gambia: Could Pleiotropy with Innate Immunity Explain Common Dizygotic Twinning in Africa?

Cited by 11 publications

References 43 publications

A prospective study of twinning and perinatal mortality in urban Guinea-Bissau

A prospective study of twinning and perinatal mortality in urban Guinea-Bissau

PTX3, a Humoral Pattern Recognition Molecule, in Innate Immunity, Tissue Repair, and Cancer

The Influence of Pentraxin 3 on the Ovarian Function and Its Impact on Fertility

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