Ovarian Follicular  Blood Flow Correlates with the Presence of Mature Dendritic Cells within the Follicle

Mika Geva 2 Adrian Ellenbogen 1 Shay Hentisteanu 3 Medeia Michaeli 1 Nechami Rotfarb 1 Mordechai Hallak 1 Ofer Fainaru 2
1Department of Obstetrics and Gynecology, IVF Unit, Hillel Yaffe Medical Center
2Department of Obstetrics and Gynecology, IVF Unit, Laboratory of Reproductive Immunology, Hillel Yaffe Medical Center
3Laboratory of Reproductive Immunology, Hillel Yaffe Medical Center
Introduction: Dendritic cells (DCs) are bone marrow derived immune cells that have been shown to promote angiogenesis.
We have recently reported that the presence of mature DCs within the ovarian follicle correlates with the ovarian response to gonadotropins.
The development of an appropriate vascular network during the follicular phase of the ovarian cycle is of primary importance for oocyte development.  
 
Aim: We sought to determine whether the presence of DCs in the ovarian follicular fluid (FF) and/ or their maturation state is correlated with follicular blood flow parameters.
 
Materials: We studied 20 patients undergoing IVF in our institution.
The first aspirated dominant follicle was measured and blood flow parameters were analyzed using pulsed Doppler US.
FF samples (n=36) were then collected, immunostained with fluorescent antibodies and analyzed by flow cytometry.
DCs were identified as CD45+CD11c+HLADR+ cells.
In order to assess DC maturity, mean fluorescent intensities (MFIs) and geometric means of individual histograms of HLADR expression on CD45+CD11c+ cells, were derived using CellQuest software.
Blood flow impedance was expressed by using the resistance index (RI) according to the formulae:
RI = (peak systolic velocity –end diastolic velocity) / Peak systolic velocity
 
Results: The percentage of CD11c+HLADR+ DCs out  total CD45+ cells within the FF was strongly correlated to both day 3 FSH levels
(r=0.853, p<0.001) and day 3 LH levels (r=0.83, p<0.0001).
Intriguingly, the resistance to ovarian follicular blood flow (RI) was inversely correlated to the maturity of DCs as indicated by the geometric mean of HLADR expression on CD11c+ cells  (r=-0.36, p=0.043).
 
Conclusions: The presence of total DCs in the follicular fluid is associated with poor ovarian reserve parameters.
In accordance to our previous findings that the presence of mature DCs within the ovarian follicle correlates with the ovarian response to gonadotropins, we now report that their presence correlates also with ovarian blood flow.
The notion that the presence of mature DCs in the ovarian follicle is important for angiogenesis and oocyte development is intriguing and warrants further investigation.  
 








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