angiotensinogen and Abortion--Spontaneous

The renin-angiotensin system is associated with angiogenesis, tissue remodeling, prenatal development, and Th2 cytokine production. The purpose of this study was to evaluate whether polymorphisms in angiotensin I-converting enzyme [ACE insertion/deletion (I/D)], angiotensinogen (AGT M235T), and angiotensin II type 1 receptor (AT1R 1166A>C) affect the prevalence of spontaneously aborted fetuses (SAFs).. One hundred and ninety-eight SAFs were <20 weeks of gestational age. The control subjects were 103 healthy children and 640 adults collected from a convenience sample. Polymerase chain reaction and restriction fragment length polymorphism analysis were performed to identify the ACE I/D, AGT M235T, and AT1R 1166A>C genotypes.. II/MM/AA, II/MT/AA, and II/TT/AC of ACE/AGT/AT1R were significantly different from controls. In particular, the statistical significance of the II/MM/AA genotype remained strong in chromosomally normal SAFs.. Our data suggest that the II/MM/AA of ACE/AGT/AT1R is a possible predisposing factor for spontaneous abortion.

Topics: Aborted Fetus; Abortion, Spontaneous; Adolescent; Angiotensinogen; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Peptidyl-Dipeptidase A; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Pregnancy; Prevalence; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Risk Factors

The purpose of this study was to evaluate the impact of angiotensinogen gene (Agt) deficiency on reproductive fitness in a rodent model. Mice with 0 (Agt(-/-)), 1 (Agt(-/+)), and 2 (Agt(+/+)) copies of Agt were bred according to the following schemes: 1) Agt(-/-) x Agt(-/-), 2) Agt(-/+) x Agt(-/+), 3) Agt(+/+) x Agt(+/+), and 4) Agt(+/+) female symbol x Agt(-/+) male symbol. There were 4 breeding pairs per scheme. Breedings were time mated. Mice and litters were weighed daily. Southern blotting was used for genotyping. We found that Agt(-/-) breeding pairs had fewer litters (2 [range 1-2] vs. 4 [range 3-5]; P = 0.01), fewer pups per litter (4 [range 1-7] vs. 6 [range 1-10]; P = 0.006), and longer interpregnancy intervals (43 days [range 31-44] vs. 35.5 days [range 22-58]; P = 0.04) compared to wild-type controls. The ratio of postcoital plugs to subsequent litters was 4.0 and 1.2 for Agt(-/-) and Agt(+/+) breedings, respectively (P = 0.03). Median maternal weights during all trimesters of pregnancy were significantly lower for Agt-deficient mice compared to wild-type controls. Among Agt(-/+) x Agt(-/+) breedings, the proportions of Agt(+/+) (n = 17), Agt(-/+) (n = 38), and Agt(-/-) (n = 4) offspring differed significantly from the expected 1:2:1 Mendelian inheritance pattern (P = 0.03). Neonatal survival among the offspring derived from the Agt(-/-) x Agt(-/-) breeding scheme was significantly reduced (P = 0. 001). We conclude that Agt deficiency is associated with an in utero lethal effect, decreased fertility, and impaired neonatal survival.

Topics: Abortion, Spontaneous; Angiotensinogen; Animals; Animals, Newborn; Embryo Loss; Female; Fertility; Genitalia, Female; Genitalia, Male; Genotype; Growth; Male; Mice; Mice, Knockout; Pregnancy; Pregnancy, Animal; Reproduction; Survival Analysis