Abstract
Study question
Bitter TasteReceptors (TAS2Rs)role in female reproductive system cells: potential implications in mechanisms underlying oocyte maturation and sperm-oocytes interaction.
Summary answer
TAS2Rs and genes involved in their transduction cascade are differentially expressed in granulosa (GCs)and cumulus cells(CCs).
What is known already
TASRs expression can be found also in extraoral location wherein their function appears less obvious. TASRs are reported to be involved in signal transduction cascade induced by chemotactic activation in spermatozoa and the expression of TAS2Rs in ejaculated human sperm has been demonstrated. The presence of these receptors in male reproductive system and in sperm gives cues to investigate their possible role in sperm-oocyte interaction. Functional implications have been collected indicating that taste receptors are also important to increase the number of highly fertilization-competent sperm cells within the female genital tract hypothesizing a role in the field of female reproduction.
Study design, size, duration
We enrolled for this study 30patients undergoing IVF cycles because of couple infertilityfrom June 2019 to October 2020at the UOSA of Assisted Reproductive techniques, Siena University Hospital(Italy).
Participants/materials, setting, methods
Female patients referring to UOSA of Assisted Reproductive techniques(median age 35 years) underwent a personalised controlled ovarian hyperstimulation protocol. After oocyte pickup, GCs were isolated from the follicular fluid through differential gradient. CCs were collected after oocytes denuding. TAS2Rs and genes involved in the transduction cascade elicited expression/localization in both GCs and CCs were confirmed by Droplet Digital PCR, western blot andimmunofluorescence.
Main results and the role of chance
For the first time, the expression and cellular localization of the TAS2Rs (TAS2R3, TAS2R4, TAS2R14, TAS2R19 and TAS2R43), their G-coupled proteins (GNAT1 orα-transducinandGNAT3 or α-gustducin) and enzymes involved in the transduction signal (PDE4A, TRPM5 and PLCB2)were demonstrated in the female reproductive system. Overall expression of TAS2Rs emerged higher in GCs than in CCs, confirming the specific molecular fingerprinting during differentiation of ovarian somatic cells. TAS2R14 is the most expressed gene in both GCs and CCs, this could account for its potential involvement in follicular cells physiology and/or for a key role of this receptor in fertilization, as supported by data showing TAS2R14 to be correlated with sperm progressive motility. We demonstrated a positive correlation in GCs between the expression of the TAS2Rs and GNAT3; interestingly, when each subset of TAS2Rs genes was correlated with the signaling gene, TAS2R14 emerged as the one with the higher correlation with GNAT3. Immunofluorescence showed different localization of TAS2Rs and their G-coupled proteins between GCs and CCs. Interestingly some of them presented some fluorescent granules, suggesting a possible involvement of proteins in membrane trafficking. Finally, results of G-coupled proteins western blot, revealed the higher expression of α-gustducin then α-transducin, confirming the gene expression.
Limitations, reasons for caution
All findings have to be validated in a larger cohort. Moreover, our data pave the way to the understanding of biological functions exerted by these receptors in the female reproductive tract.
Wider implications of the findings
Further studies might contribute to better understanding the physiologic role of taste receptorsfemale reproductive system. This should becrucial to clarify the role of these receptors in maturation or competence acquiring of oocytes, or also in sperm-oocytes attraction and recognition, crucial point in fertilization process
Trial registration number
Not applicable
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