Overarching Research Questions
How are steroid hormones like estrogen and progesterone modulate the function of the oviduct during sperm transport, fertilization, and pre-implantation embryo development in mammals?
Can the blockade of semen liquefaction process be used as a non-hormonal, women-controlled, on-demand contraceptive method? If so, how efficient is it?
Roles of estrogen and progesterone in the oviductal function
Estrogen and progesterone work in an opposing manner to regulate embryo transport in the oviduct by governing the oviductal fluid flow, ciliary activity, and muscle contractility. See more detail in our review article in Reproduction
Ciliary beating in the mouse oviduct
It is incredible how different epithelial cell types in different tissues work! This video shows the beating of ciliated epithelial cells from the mouse oviduct collected on the first day of pregnancy (right after fertilization). The cilia beat in a unidirectional fashion to propel the fluid (and potentially embryo) from the oviduct to the uterus. The video was recorded real-time at 100 frames/second for 10 seconds.
Signaling cascade of kallikrein 3 (KLK3) activation during the liquefaction process.
Pro-KLKs are secreted into the prostatic fluid. High concentration of Zn2+ in prostatic fluid inactivates KLK3 activity. After ejaculation, prostatic and seminal vesicle fluids are combined. SEMGs are available to sequester Zn2+ as SEMGs have higher affinity to Zn2+ compared to KLKs. Pro-KLK5 undergoes autocleavage to rid of pro-peptide sequences and autoactivates. Subsequently, KLK5 activates pro-KLK2 and 3. KLK2 also potentially activates pro-KLK3. Activated KLK3 then hydrolyzes SEMGs into smaller fractions. After hydrolysis, semen becomes liquefied and sperm gain their motility to transport to the upper female reproductive tract for fertilization. See more detail in our review article in Biology of Reproduction.
Treatment of serine protease inhibitor leads to hyperviscosity in human semen
Our recent findings show that inhibition of PSA using PSA neutralizing antibody prevents human semen liquefaction process. This inhibition has led to a hyperviscous semen. However, it is still unclear how effective it would be to use this method in the female reproductive tract. We are currently testing it in mammalian models.