TY - JOUR
T1 - Intracytoplasmic sperm injection induces transgenerational abnormalities in mice
AU - Kanatsu-Shinohara, Mito
AU - Shiromoto, Yusuke
AU - Ogonuki, Narumi
AU - Inoue, Kimiko
AU - Hattori, Satoko
AU - Miura, Kento
AU - Watanabe, Naomi
AU - Hasegawa, Ayumi
AU - Mochida, Keiji
AU - Yamamoto, Takuya
AU - Miyakawa, Tsuyoshi
AU - Ogura, Atsuo
AU - Shinohara, Takashi
N1 - Publisher Copyright:
© 2023, Kanatsu-Shinohara et al.
PY - 2023/11/15
Y1 - 2023/11/15
N2 - In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are 2 major assisted reproductive techniques (ARTs) used widely to treat infertility. Recently, spermatogonial transplantation emerged as a new ART to restore fertility to young patients with cancer after cancer therapy. To examine the influence of germ cell manipulation on behavior of offspring, we produced F1 offspring by a combination of two ARTs, spermatogonial transplantation and ICSI. When these animals were compared with F1 offspring produced by ICSI using fresh wild-type sperm, not only spermatogonial transplantation–ICSI mice but also ICSI-only control mice exhibited behavioral abnormalities, which persisted in the F2 generation. Furthermore, although these F1 offspring appeared normal, F2 offspring produced by IVF using F1 sperm and wild-type oocytes showed various types of congenital abnormalities, including anophthalmia, hydrocephalus, and missing limbs. Therefore, ARTs can induce morphological and functional defects in mice, some of which become evident only after germline transmission.
AB - In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are 2 major assisted reproductive techniques (ARTs) used widely to treat infertility. Recently, spermatogonial transplantation emerged as a new ART to restore fertility to young patients with cancer after cancer therapy. To examine the influence of germ cell manipulation on behavior of offspring, we produced F1 offspring by a combination of two ARTs, spermatogonial transplantation and ICSI. When these animals were compared with F1 offspring produced by ICSI using fresh wild-type sperm, not only spermatogonial transplantation–ICSI mice but also ICSI-only control mice exhibited behavioral abnormalities, which persisted in the F2 generation. Furthermore, although these F1 offspring appeared normal, F2 offspring produced by IVF using F1 sperm and wild-type oocytes showed various types of congenital abnormalities, including anophthalmia, hydrocephalus, and missing limbs. Therefore, ARTs can induce morphological and functional defects in mice, some of which become evident only after germline transmission.
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U2 - 10.1172/JCI170140
DO - 10.1172/JCI170140
M3 - Article
C2 - 37966118
AN - SCOPUS:85177093730
SN - 0021-9738
VL - 133
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 22
M1 - e170140
ER -
