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BEGIN:VEVENT
DTSTAMP:20260510T054915Z
DTSTART;VALUE=DATE-TIME:20210624T133000
DTEND;VALUE=DATE-TIME:20210624T143000
SUMMARY:BMS Divisional Webinar: Endometrial Bone Marrow-derived Progenito
 r Cells: Contribution to Embryo Implantation\, Pregnancy and Beyond\, Dr
  Reshef Tal\, Division of Reproductive Endocrinology and Infertility\, Y
 ale School of Medicine
TZID:Europe/London
UID:20210624-8a17841b7a2d9966017a341c3f8144fe@warwick.ac.uk
CREATED:20210622T142504Z
DESCRIPTION:Abstract: The decidua is a transient uterine tissue shared by
  mammals with hemochorial placenta and is essential for pregnancy. The d
 ecidua is infiltrated by many immune cells promoting pregnancy. Bone mar
 row-derived progenitor cells (BMDPC) contribute to various nonhematopoie
 tic cell populations in the endometrium but their role in reproduction h
 as been unknown. We developed a non-gonadotoxic bone marrow transplantat
 ion mouse model for studying BM-derived cell (BMDC) trafficking in repro
 duction. Our objectives were to characterize the spatiotemporal contribu
 tion of BMDPCs to the decidua\, explore their functional importance to i
 mplantation and pregnancy\, and study the role of CXCR4-CXCL12 axis in m
 ediating their recruitment to the pregnant uterus. To investigate the no
 nhematopoietic physiologic contribution of BMDC to decidua\, we utilized
  our reported 5-fluorouracil-based non-gonadotoxic bone marrow transplan
 t (BMT) regimen to transplant BM from GFP donors into wild-type (WT) C57
 BL6/J female mice (~45% donor chimerism). Detailed characterization of G
 FP-labeled BMDC in the uterus throughout gestation was performed. To exp
 lore the functional importance of BMDPC to implantation and pregnancy\, 
 we performed BMT experiments in Homeobox A11 (Hoxa11) genetic knockout (
 KO) mice models which are associated with endometrial stromal defects le
 ading to decidualization failure in homozygous (KO)\, and pregnancy loss
  in heterozygous (+/-) mice. In addition\, to investigate the role of CX
 CL12-CXCR4 axis in mediating recruitment of BMDCs to the pregnant uterus
 \, we developed BM-specific CXCR4 KO (tamoxifen-inducible Cre) mice. We 
 show that pregnancy mobilizes mesenchymal BMDCs to the circulation and i
 nduces considerable adult BMDCs recruitment to decidua\, where some diff
 erentiate into nonhematopoietic prolactin-expressing decidual cells. To 
 explore the functional importance of nonhematopoietic BMDPCs to pregnanc
 y\, we used Hoxa11-deficient mice\, having endometrial stromal-specific 
 defects precluding decidualization and successful pregnancy. Hoxa11 expr
 ession in BM is restricted to nonhematopoietic cells. BM transplant (BMT
 ) from wild-type (WT) to Hoxa11-/- mice results in stromal expansion\, g
 land formation\, and marked decidualization otherwise absent in Hoxa11-/
 - mice. Moreover\, in Hoxa11+/- mice\, which have increased pregnancy lo
 sses\, BMT from WT donors leads to normalized uterine expression of nume
 rous decidualization-related genes and rescue of pregnancy loss. Single 
 cell RNAseq analysis of E9.5 implantation site identified GFP+ BM-derive
 d cells in decidual stromal cell (DSC) clusters expressing multiple mese
 nchymal/stromal markers similar to resident DSCs and without expression 
 of hematopoietic markers\, confirming their mesenchymal lineage. Knockou
 t of CXCR4 in BM cells led to inhibition of recruitment of nonhematopiet
 ic BMDCs to the pregnant uterus. Collectively\, these findings reveal th
 at adult BMDCs have a previously unrecognized nonhematopoietic physiolog
 ic contribution to decidual stroma\, thereby playing important roles in 
 decidualization and pregnancy. The receptor CXCR4 plays an important rol
 e in mediating recruitment of nonhematopoietic BMDCs to the pregnant dec
 idua. Biography: Dr. Reshef Tal is Assistant Professor of Obstetrics and
  Gynecology and Reproductive Sciences at the Yale School of Medicine and
  a Women’s Reproductive Health Research (WRHR) Scholar. He obtained his 
 M.D. and Ph.D. in Molecular Biology at Sackler School of Medicine in Tel
 -Aviv University\, Israel. Following a postdoctoral research fellowship 
 at the Lunenfeld Research Institute at the University of Toronto\, he co
 mpleted his residency in Obstetrics and Gynecology at Maimonides Medical
  Center\, NY\, followed by a fellowship in Reproductive Endocrinology an
 d Infertility at Yale University. His laboratory is focused on investiga
 ting the role of bone marrow-derived progenitor cells and immune cells i
 n embryo implantation and pregnancy maintenance with the ultimate goal o
 f developing new therapies for patients with infertility. His clinical i
 nterests include infertility\, IVF\, polycystic ovarian syndrome (PCOS)\
 , recurrent pregnancy loss (RPL) and endometrial pathologies including A
 sherman’s syndrome\, thin endometrium and implantation failure. Dr. Tal 
 is the recipient of many research awards including the New England Ferti
 lity Society/Ferring Fellow Research Award\, the Society of Reproductive
  Endocrinology & Infertility (SREI)/American Society for Reproductive Me
 dicine (ASRM) Fellow Research Award\, Patterson Trust Fellow Award\, Soc
 iety for Reproductive Investigation (SRI) President's Plenary Award and 
 the Albert S. McKern Award. Dr. Tal has published over 60 peer-reviewed 
 scientific articles\, authored five book chapters and also edited a book
  (Antimullerian Hormone: Biology\, Role in Ovarian Function and Clinical
  Significance). In addition\, he serves as an Associate Editor for the j
 ournal Reproductive Biology and Endocrinology.
LOCATION:via Teams
CATEGORIES:BiomedicalSciences,DivisionalSeminars
LAST-MODIFIED:20210622T142504Z
ORGANIZER;CN=Jas Bains:
END:VEVENT
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