Jing-Hui Lei1, Xiaokui Yang, Sha Peng, Ying Li, Caroline Underhill, Cheng Zhu, Hai-Yan Lin, Hongmei Wang, Geoffrey L Hammond. 1. State Key Laboratory of Reproductive Biology, Institute of Zoology (J.-H.L., C.Z., H.-Y.L., H.W.), Chinese Academy of Sciences, Beijing 100101, China; Department of Human Reproductive Medicine (X.Y., S.P., Y.L.), Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China; and Department of Cellular and Physiological Sciences, Faculty of Medicine (C.U., G.L.H.), the University of British Columbia, Vancouver V6T 1Z3, Canada.
Abstract
CONTEXT: Plasma corticosteroid-binding globulin (CBG) transports cortisol but high progesterone levels at the maternal-fetal interface can displace cortisol from its steroid-binding site. A secretion-deficient CBG mutant (A51V) in ∼1 of 36 Chinese causes low circulating CBG levels. OBJECTIVE: Assess the implications of a CBG deficiency on pregnancy outcomes. PARTICIPANTS AND DESIGN: From 1978 Chinese women screened at 12-16 weeks' gestation, 50 A51V carriers were identified and 46 were followed with 60 controls throughout pregnancy. Blood samples from another 2051 pregnant women were obtained at term to determine the secondary sex ratio (SSR) of newborns in an extended cohort (n = 101) of A51V mothers. OUTCOME MEASURES AND RESULTS: Among women recruited at 12-16 weeks' gestation, serum CBG increased progressively during pregnancy but was lower (P < .0001) in heterozygous A51V carriers than controls. Two women homozygous for A51V had very low serum CBG but their pregnancies progressed normally. The A51V mothers did not differ from controls in body mass index, gestational age at delivery, duration of parturition, blood pressure, gravidity, infant birth weight and size, or placental weights, and reported no unusual clinical symptoms. Peripheral CBG and progesterone levels correlated (r = 0.459) during first and second trimesters. Progesterone levels were much higher in intervillous blood and correlated (r = 0.637) with CBG levels. A female-skewed SSR in newborns of A51V mothers (0.77) differed (P < .05) from the SSR (1.17) in a reference cohort. CONCLUSIONS: CBG influences progesterone levels in peripheral blood and at the maternal-fetal interface. The female-skewed SSR suggests that male fetal survival is compromised in CBG-deficient mothers.
CONTEXT: Plasma corticosteroid-binding globulin (CBG) transports cortisol but high progesterone levels at the maternal-fetal interface can displace cortisol from its steroid-binding site. A secretion-deficient CBG mutant (A51V) in ∼1 of 36 Chinese causes low circulating CBG levels. OBJECTIVE: Assess the implications of a CBG deficiency on pregnancy outcomes. PARTICIPANTS AND DESIGN: From 1978 Chinese women screened at 12-16 weeks' gestation, 50 A51V carriers were identified and 46 were followed with 60 controls throughout pregnancy. Blood samples from another 2051 pregnant women were obtained at term to determine the secondary sex ratio (SSR) of newborns in an extended cohort (n = 101) of A51V mothers. OUTCOME MEASURES AND RESULTS: Among women recruited at 12-16 weeks' gestation, serum CBG increased progressively during pregnancy but was lower (P < .0001) in heterozygous A51V carriers than controls. Two women homozygous for A51V had very low serum CBG but their pregnancies progressed normally. The A51V mothers did not differ from controls in body mass index, gestational age at delivery, duration of parturition, blood pressure, gravidity, infant birth weight and size, or placental weights, and reported no unusual clinical symptoms. Peripheral CBG and progesterone levels correlated (r = 0.459) during first and second trimesters. Progesterone levels were much higher in intervillous blood and correlated (r = 0.637) with CBG levels. A female-skewed SSR in newborns of A51V mothers (0.77) differed (P < .05) from the SSR (1.17) in a reference cohort. CONCLUSIONS:CBG influences progesterone levels in peripheral blood and at the maternal-fetal interface. The female-skewed SSR suggests that male fetal survival is compromised in CBG-deficient mothers.
Authors: Emily J Meyer; David J Torpy; Anastasia Chernykh; Morten Thaysen-Andersen; Marni A Nenke; John G Lewis; Harinda Rajapaksha; Wayne Rankin; Steven W Polyak Journal: Protein Sci Date: 2020-11-04 Impact factor: 6.725
Authors: Marni A Nenke; Anna Zeng; Emily J Meyer; John G Lewis; Wayne Rankin; Julie Johnston; Svjetlana Kireta; Shilpanjali Jesudason; David J Torpy Journal: J Endocr Soc Date: 2017-02-13