Leukocyte telomere length in children born following blastocyst-stage embryo transfer

Wang C, Gu Y, Zhou J, Zang J, Ling X, Li H, Hu L, Xu B, Zhang B, Qin N, Lv H, Duan W, Jiang Y, He Y, Jiang T, Chen C, Han X, Zhou K, Xu B, Liu X, Tao S, Jiang Y, Du J, Dai J, Diao F, Lu C, Guo X, Huo R, Liu J, Lin Y, Xia Y, Jin G, Ma H, Shen H, Hu Z

doi:10.1038/s41591-022-02108-3

Abstract

1. Nat Med. 2022 Dec;28(12):2646-2653. doi: 10.1038/s41591-022-02108-3. Epub 2022 Dec 15.

Leukocyte telomere length in children born following blastocyst-stage embryo transfer.

Wang C(#)(1)(2)(3), Gu Y(#)(1)(2), Zhou J(#)(2), Zang J(#)(2), Ling X(#)(1)(4), Li H(#)(1)(5), Hu L(6), Xu B(7), Zhang B(8), Qin N(1)(2), Lv H(1)(9), Duan W(3), Jiang Y(1)(2), He Y(1)(2), Jiang T(1)(10), Chen C(2), Han X(1)(2), Zhou K(1)(2), Xu B(1)(2), Liu X(1)(2), Tao S(1)(2), Jiang Y(1)(2), Du J(1)(2), Dai J(1)(2), Diao F(1)(11), Lu C(1)(12), Guo X(1), Huo R(1), Liu J(1)(9)(11), Lin Y(1)(9)(13), Xia Y(1)(12), Jin G(1)(2)(9), Ma H(1)(2)(9), Shen H(1)(2)(9), Hu Z(14)(15)(16).

Author information: (1)State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China. (2)Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China. (3)Department of Bioinformatics, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, Jiangsu, China. (4)Department of Reproduction, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China. (5)Reproductive Genetic Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China. (6)Department of Reproduction, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, China. (7)Reproductive Medicine Center, Tongji Hospital, Tongji Medicine College, Huazhong University of Science and Technology, Wuhan, Hubei, China. (8)Center for Reproductive Medicine, The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China. (9)State Key Laboratory of Reproductive Medicine (Suzhou Centre), The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China. (10)Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China. (11)Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China. (12)Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China. (13)Department of Maternal, Child and Adolescent Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China. (14)State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China. zhibin_hu@njmu.edu.cn. (15)Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China. zhibin_hu@njmu.edu.cn. (16)State Key Laboratory of Reproductive Medicine (Suzhou Centre), The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China. zhibin_hu@njmu.edu.cn. (#)Contributed equally

Comment in Nat Med. 2022 Dec;28(12):2476-2477. doi: 10.1038/s41591-022-02098-2.

Perinatal and childhood adverse outcomes associated with assisted reproductive technology (ART) has been reported, but it remains unknown whether the initial leukocyte telomere length (LTL), which is an indicator of age-related phenotypes in later life, is affected. Here, we estimated the LTLs of 1,137 individuals from 365 families, including 202 children conceived by ART and 205 children conceived spontaneously from two centers of the China National Birth Cohort, using whole-genome sequencing (WGS) data. One-year-old children conceived by ART had shorter LTLs than those conceived spontaneously (beta, -0.36; P = 1.29 × 10-3) after adjusting for plurality, sex and other potential confounding factors. In particular, blastocyst-stage embryo transfer was associated with shorter LTL (beta, -0.54, P = 2.69 × 10-3) in children conceived by ART. The association was validated in 586 children conceived by ART from five centers using different LTL quantification methods (that is, WGS or qPCR). Blastocyst-stage embryo transfer resulted in shorter telomere lengths in mice at postnatal day 1 (P = 2.10 × 10-4) and mice at 6 months (P = 0.042). In vitro culturing of mice embryos did not result in shorter telomere lengths in the late cleavage stage, but it did suppress telomerase activity in the early blastocyst stage. Our findings demonstrate the need to evaluate the long-term consequences of ART, particularly for aging-related phenotypes, in children conceived by ART.

DOI: 10.1038/s41591-022-02108-3 PMID: 36522605 [Indexed for MEDLINE]