Research

Our lab aims to understand cellular and molecular mechanisms underlying sexual differentiation of reproductive tracts. Before sexual differentiation, both primitive male and female reproductive tracts co-exist in an embryo. During sexual differentiation, the embryo eliminates one of the two primitive reproductive tracts and maintains exclusively the one matching to its sex. The retained sex-specific tract eventually differentiates into a functional organ in the adult reproductive system. Sexual differentiation and function of reproductive tracts are regulated/influenced by actions of sex hormones. Therefore, during differentiation, the male and female reproductive tract must acquire/develop proper responsiveness to sex hormones; environmental chemicals mimicking sex hormones can have adverse effects on reproductive tract differentiation. We are particularly interested in and focus on understanding mechanisms underlying the above phenomena:

1. How are sex-specific fates of two primitive reproductive tracts regulated?
2. How does the male and female reproductive tract acquire/develop proper responsiveness to male and female sex hormones, respectively?
3. How do environmental chemicals that interfere with sex hormone signaling affect reproductive tract differentiation?

We address these questions by utilizing transgenic and conditional knockout mouse models, ex vivo organ culture, gene/protein expression analyses, genomic and single-cell technologies. Disruptions in reproductive tract differentiation can lead to disorders of sex development and jeopardize an individual’s future reproductive potential. Our research will provide fundamental knowledge for the development of better strategies for prevention, diagnosis and treatment of related disorders of sex development and reproductive diseases.

Publications

• Zhao F, Yao HH. A tale of two tracts: history, current advances, and future directions of research on sexual differentiation of reproductive tracts†. Biol Reprod. 2019 Sep 1;101(3):602-616. doi: 10.1093/biolre/ioz079. PubMed PMID: 31058957; PubMed Central PMCID: PMC6791057.
• Zhao F, Franco HL, Rodriguez KF, Brown PR, Tsai MJ, Tsai SY, Yao HH. Elimination of the male reproductive tract in the female embryo is promoted by COUP-TFII in mice. Science. 2017 Aug 18;357(6352):717-720. doi: 10.1126/science.aai9136. PubMed PMID: 28818950; PubMed Central PMCID: PMC5713893.
• Zhao F, Zhou J, Li R, Dudley EA, Ye X. Novel function of LHFPL2 in female and male distal reproductive tract development. Sci Rep. 2016 Mar 11;6:23037. doi: 10.1038/srep23037. PubMed PMID: 26964900; PubMed Central PMCID: PMC4786858.
• Zhao F, Zhou J, El Zowalaty AE, Li R, Dudley EA, Ye X. Timing and recovery of postweaning exposure to diethylstilbestrol on early pregnancy in CD-1 mice. Reprod Toxicol. 2014 Nov;49:48-54. doi: 10.1016/j.reprotox.2014.07.072. Epub 2014 Jul 22. PubMed PMID: 25062584; PubMed Central PMCID: PMC4303565.
• Zhao F, Li R, Xiao S, Diao H, El Zowalaty AE, Ye X. Multigenerational exposure to dietary zearalenone (ZEA), an estrogenic mycotoxin, affects puberty and reproduction in female mice. Reprod Toxicol. 2014 Aug;47:81-8. doi: 10.1016/j.reprotox.2014.06.005. Epub 2014 Jun 24. PubMed PMID: 24972337; PubMed Central PMCID: PMC4137769.