Early pregnancy establishment, especially successful of embryo implantation, is the cornerstone of reproduction, and determines the pregnancy outcome. It has been reported that 75% of pregnancy losses are rooted in peri-implantation period. Our lab studies the regulation of early pregnancy including: how the embryo develops into normal blastocyst and transports into uterus timely; how uterus gets the receptivity; and the precise communication of embryo and uterus. We wanted to reveal the key regulator and mechanism in early pregnancy establishment from mouse model, that is close to our own, human pregnancy.

Figure 1. Overview of the process of human early pregnancy (cited from Nat Rev Genet, 2006)

Focus 1 Regulation of embryo and uterus communication

After blastocyst enters into uterus, the crosstalk between an embryo and the uterus determines when and where the embryo implants into the uterus. A precisely regulated intrauterine environment is responsible for pregnancy establishment, and disruption of the uterine fluid homeostasis during this process can cause abnormal embryo implantation and pregnancy loss. We wanted to identify the key molecules in uterine environment that mediate blastocyst and uterus communication.

Figure 2. Uterine fluid environment mediates the crosstalk between an embryo and uterus.

Focus 2 Maternal environmental exposure epigenetically influence embryo development and fetus health 

Certain maternal lifestyle factors, such as environmental exposure and nutritional condition, can directly affect embryonic development and result in offspring metabolic disorders and disease predispositions. However, how maternally acquired environmental traits influence a developing embryo in the uterus remains unresolved. Peri-implantation is a critical time window during which the developing embryo can be regulated or affected by active molecules in the uterus and we propose that maternal environmental exposure during this period may be transferred to an embryo, which might result in long-term effects on offspring well-being.

Figure 3. Maternal environmental exposure might epigenetically influence embryo development and fetus health

Focus 3 New technology of reproduction study 

Reproduction is a traditional field, but with technological development, new studying methods which are applied into recent studies, rekindled great interests in this old yet fascinating field. For example, deep imaging provides more information about reproductive system and bring more possibility to open the black box of fertilization and pregnancy.

Figure 4. Group photo

Selected publications:

1. Qian J, Zhang Y, Qu Y, Zhang L, Shi J, Zhang X, Liu S, Bo H, Sung J, Zhou T, Chen Q, Sean M, Duan E^*, Zhang Y^*.(2018). Caffeine consumption during early pregnancy impairs oviductal embryo transport, embryonic development and uterine receptivity in mice. Biology of Reprodcution.0(0):1-10.

2. Zhang Y^#, Zhang X^#, Shi J^#, Tuorto F^#, Li X^#, Liu Y, Liebers R, Zhang L, Qu Y, Qian J, Pahima M, Liu Y, Yan M, Cao Z, Lei X, Cao Y, Peng H, Liu S, Wang Y, Zheng H, Woolsey R, Quilici D, Zhai Q, Li L, Zhou T, Yan W, Lyko F, Zhang Y^*, Zhou Q^*, Duan E^*, Chen Q^*. (2018). Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs. Nature Cell Biology. 20:535-540.

3. Zhang Y^#, Wang Q^#, Wang H, Duan E.(2017). Uterine Fluid in Pregnancy: A Biological and Clinical Outlook. Trends in Molecular Medicine. 7:604-614.

4. Chen Q, Yan M, Cao Z, Li X, Zhang Y, Shi J, Feng G, Peng H, Zhang X, Zhang Y, Qian J, Duan E^*, Zhai Q^*, Zhou Q^*. (2016). Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science. 351(6271):397-400.

5. Zhang Y^#, Chen Q^#, Zhang H^#, Wang Q^#, Li R, Jin Y, Wang H, Ma T, Qiao J, Duan E. (2015). Aquaporin-dependent excessive intrauterine fluid accumulation is a major contributor in hyper-estrogen induced aberrant embryo implantation. Cell Research. 25(1):139-42.

6. Shi J, Chen Q, Li X, Zheng X, Zhang Y, Qiao J, Tang F, Tao Y, Zhou Q, Duan E. (2015). Dynamic transcriptional symmetry-breaking in pre-implantation mammalian embryo development revealed by single-cell RNA-seq. Development. 142:3468-3477.

7. Zhang Y^#, Zhang Y^#, Shi J^#, Zhang H, Cao Z, Gao X, Ren W, Ning Y, Ning L, Cao Y, Chen Y, Ji W, Chen ZJ, Chen Q, Duan E. (2014). Identification and characterization of an ancient class of small RNAs enriched in serum associating with active infection. Journal of Molecular Cell Biology. 6(2):172-174.

8. Chen Q^#, Zhang Y^#, Elad D, Jaffa AJ, Cao Y, Ye X, Duan E. (2013). Navigating the site for embryo implantation: biomechanical and molecular regulation of intrauterine embryo distribution. Molecular Aspects of Medicine. 34(5):1024-42.

9. Chen Q^#, Zhang Y^#, Peng H, Lei L, Kuang H, Zhang L, Ning L, Cao Y, Duan E. (2011). Transient {beta}2-adrenoceptor activation confers pregnancy loss by disrupting embryo spacing at implantation. Journal of Biology Chemistry. 286:4349-4356.