皮质类固醇结合球蛋白缺乏对妊娠及新生儿性别的影响。

Impact of corticosteroid-binding globulin deficiency on pregnancy and neonatal sex.

作者信息

Lei Jing-Hui, Yang Xiaokui, Peng Sha, Li Ying, Underhill Caroline, Zhu Cheng, Lin Hai-Yan, Wang Hongmei, Hammond Geoffrey L

机构信息

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.

出版信息

J Clin Endocrinol Metab. 2015 May;100(5):1819-27. doi: 10.1210/jc.2014-4254. Epub 2015 Feb 19.

DOI:10.1210/jc.2014-4254

PMID:25695888

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.

摘要

背景

血浆皮质类固醇结合球蛋白（CBG）可转运皮质醇，但母胎界面处高水平的孕酮可将皮质醇从其类固醇结合位点上置换下来。在中国，每36人中约有1人存在分泌缺陷型CBG突变体（A51V），导致循环中CBG水平较低。

目的

评估CBG缺乏对妊娠结局的影响。

参与者与设计

在1978名妊娠12 - 16周时接受筛查的中国女性中，识别出50名A51V携带者，并在整个孕期对其中46名携带者和60名对照进行随访。从另外2051名孕妇足月时采集血样，以确定A51V母亲的一个扩大队列（n = 101）中新生儿的次生性别比（SSR）。

结果测量指标与结果

在妊娠12 - 16周时招募的女性中，血清CBG在孕期逐渐升高，但杂合子A51V携带者的血清CBG水平低于对照组（P < 0.0001）。两名A51V纯合子女性的血清CBG水平极低，但她们的妊娠进展正常。A51V母亲在体重指数、分娩时的孕周、分娩持续时间、血压、妊娠次数、婴儿出生体重和大小或胎盘重量方面与对照组无差异，且未报告异常临床症状。孕早期和孕中期外周CBG与孕酮水平相关（r = 0.459）。绒毛间隙血中的孕酮水平高得多，且与CBG水平相关（r = 0.637）。A51V母亲所生新生儿的女性偏态SSR（0.77）与参考队列中的SSR（1.17）不同（P < 0.05）。