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 effective is it?
The detailed method on the collection of preimplantation embryos from mouse oviduct and uterus
In this study, female mice at estrus were mated overnight with a proven male, and the presence of a copulatory plug the next morning was recorded as 0.5 days post coitum (dpc). By 09:30 h on 0.5 dpc, both oviducts were dissected to isolate cumulus-oocyte complexes. Zygotes were identified at the pronuclear stage. The oviducts were then excised at 1.5 dpc and 2.5 dpc to retrieve 2-cell and 4- to 8-cell embryos using a blunted 30-G needle filled with Leibovitz-15 medium plus 1% fetal bovine serum. At 3.5 dpc, both the oviduct and uterus were flushed for morula and blastocyst stage embryos. Paper here.
The review article on dynamic roles of the oviduct as a biosensor for the preimplantation embryo development
In this review, we provide evidence supporting the oviduct as an active regulator of preimplantation embryonic development, discuss the consequences of bypassing the oviduct in ART, and highlight current experimental models and knowledge gaps. Defining how the oviduct functions as a biosensor of embryo quality will be critical for understanding early pregnancy loss and refinements for ARTs. Check out the accepted article here.
Generation of combined epithelial and stromal cells from the mouse and human oviducts to assembloids for in vitro studies
In collaboration with Drs. Andrew Kelleher and Mark Hunter at the MU School of Medicine, Kalli, our graduate student, generated the oviduct assembloids from mouse and human tissues to study the function of the oviduct in vitro. Check out the detailed protocol in the preprint here
Maternal-derived extracellular vesicles (EVs) can be visualized in 8-cell embryos in vivo
Using the CD9-GFP report specifically in the epithelial cells of the oviduct, we found that physiological condition of maternal-derived extracellular vesicles (EVs) can be incorporated into 8-cell embryos in vivo. Our data suggest that factors from maternal tissues communicate with embryos during preimplantation period in mice. Check out Kalli's publication here
Our contraceptive research was highlighted by Male Contraceptive Initiative
Our work on the non-hormonal contraceptive development was highlighted by Male Contraceptive Initiative. We aim to inhibit semen liquefaction process by blocking the activity of prostate specific antigen.
Gene search function in single cell RNA-seq in mouse oviducts
Get access to all of our published scRNA-seq data from mouse oviduct that were treated with estradiol after ovariectomy, at estrus stage, or from human Fallopian tubes. https://genes.winuthayanon.com/
Proper estrogen signaling is required in the oviduct to maintain embryo membrane integrity
Female mice with the deletion of estrogen receptor alpha (ESR1) in the epithelial cells are infertile, partly due to detrimental microenvironment in the oviduct. Video here. See more detail in eLIFE.
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
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.
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.
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.