title: IVF affects embryonic development in a sex-biased manner in mice.
abstract: Increasing evidence indicates that IVF (IVF includes in vitro fertilization and culture) embryos and babies are associated with a series of health complications, and some of them show sex-dimorphic patterns. Therefore, we hypothesized that IVF procedures have sex-biased or even sex-specific effects on embryonic and fetal development. Here, we demonstrate that IVF-induced side effects show significant sexual dimorphic patterns from the pre-implantation to the prenatal stage. During the pre-implantation stage, female IVF embryos appear to be more vulnerable to IVF-induced effects, including an increased percentage of apoptosis (7.22 ± 1.94 vs 0.71 ± 0.76, P<0.01), and dysregulated expression of representative sex-dimorphic genes (Xist, Hprt, Pgk1 and Hsp70). During the mid-gestation stage, IVF males had a higher survival rate than IVF females at E13.5 (male:female=1.33:1), accompanied with a female-biased pregnancy loss. In addition, while both IVF males and females had reduced placental vasculogenesis/angiogenesis, the compensatory placental overgrowth was more evident in IVF males. During the late-gestation period, IVF fetuses had a higher sex ratio (male:female=1.48:1) at E19.5, and both male and female IVF placentas showed overgrowth. After birth, IVF males grew faster than their in vivo (IVO) counterparts, while IVF females showed a similar growth pattern with IVO females. The present study provides a new insight into understanding IVF-induced health complications during embryonic and fetal development. By understanding and minimizing these sex-biased effects of the IVF process, the health of IVF-conceived babies may be improved in the future.
authors.affiliation: Key Laboratory of Animal GeneticsBreeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, No. 2 Yuanminyuan West Road, Beijing 100193, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tan
authors.affiliation: Key Laboratory of Animal GeneticsBreeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, No. 2 Yuanminyuan West Road, Beijing 100193, People's Republic of China.
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal GeneticsBreeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, No. 2 Yuanminyuan West Road, Beijing 100193, People's Republic of China.
authors.forename: Zhenni
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal GeneticsBreeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, No. 2 Yuanminyuan West Road, Beijing 100193, People's Republic of China anleim@cau.edu.cn tianjh@cau.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: An
authors.affiliation: Key Laboratory of Animal GeneticsBreeding and Reproduction of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, No. 2 Yuanminyuan West Road, Beijing 100193, People's Republic of China anleim@cau.edu.cn tianjh@cau.edu.cn.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Tian
mesh_terms: D000818:Animals; D004624:Embryo Transfer; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D047109:Fetal Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D012727:Sex Characteristics; D012744:Sex Ratio