TY - JOUR
T1 - Chronic low-dose antiprogestin impairs preimplantation embryogenesis, but not oocyte nuclear maturation or fertilization in rhesus monkeys
AU - Borman, Sherri M.
AU - Chwalisz, Kristof
AU - Stouffer, Richard L.
AU - Zelinski-Wooten, Mary B.
N1 - Funding Information:
The generous provision of ZK 137 316 by Schering AG (Berlin, Germany) and recombinant human gonadotropins by Ares Serono are acknowledged. The authors are grateful to the dedicated and conscientious staff of the Division of Animal Resources and the surgical team for their enthusiastic participation in this study. We also thank Maralee Lawson, Andrea Widmann-Browning, Jessica Vance, and Sherri Thormahlen for technical assistance; Dr. Don Wolf, Carrie Greenburg, Santiago Vega, and Christine Gagliardi of the Assisted Reproductive Technologies Core for media and sperm preparation; Dr. David Hess, Mark Poroli, and Rachel Dykman of the Endocrine Services Laboratory for hormone analyses; Dr. Anda Cornea of the Morphology Core with Confocal Microscopy assistance. This research was supported by NICHD/NIH through cooperative agreement [U54 18185] as part of the Specialized Cooperative Centers Program in Reproductive Research and National Institute of Health Grants HD31633 (M.B.Z.-W.), 2T32 HDO7133 (S.M.B.), and RR00163.
PY - 2003/11
Y1 - 2003/11
N2 - Continual administration of low doses of the antiprogestin ZK137316 permits ovarian/menstrual cyclicity, but prevents pregnancy in female rhesus monkeys. The sites of contraceptive action remain unknown. This study determined whether chronic, low-dose antiprogestin exposure during follicular development impairs oocyte maturation in vivo, as well as fertilization and preimplantation embryogenesis in vitro. Adult, female rhesus monkeys exhibiting normal menstrual cycles received vehicle (n=9) or 0.03mg ZK137316 (n=8)/kg body weight i.m. daily for 3 months. Controlled ovarian stimulation with recombinant gonadotropins was initiated in the 3rd month. Oocytes collected from preovulatory follicles were evaluated for nuclear maturity and inseminated in vitro. Preimplantation embryonic development was monitored in vitro. The total number of oocytes and percentage collected at each nuclear stage were similar in both groups. More (P<0.05) atretic oocytes were recovered following antiprogestin relative to vehicle treatment. Fertilization rates and percentages of embryos that progressed to the morula stage were similar between groups, but antiprogestin-treated females exhibited less (P<0.05) normal cleavage. Embryonic development was accelerated by 1 day (P<0.05) from the 16-cell to the morula stage in the antiprogestin group relative to vehicle. Despite this, the majority of embryos became blastocysts within 6 days in vitro in the antiprogestin group, but fewer expanded (P=0.09) and hatched (P<0.05) compared to vehicle. During in vivo treatment with chronic, low-dose antiprogestin, oocytes retained their ability to resume and complete meiosis as well as fertilize following insemination in vitro. However, preimplantation embryogenesis in vitro was impaired, particularly during the later stages of blastocyst development. Thus, antiprogestin exposure during follicular development altered oocyte functions that are critical for normal preimplantation embryogenesis; this may contribute to pregnancy prevention.
AB - Continual administration of low doses of the antiprogestin ZK137316 permits ovarian/menstrual cyclicity, but prevents pregnancy in female rhesus monkeys. The sites of contraceptive action remain unknown. This study determined whether chronic, low-dose antiprogestin exposure during follicular development impairs oocyte maturation in vivo, as well as fertilization and preimplantation embryogenesis in vitro. Adult, female rhesus monkeys exhibiting normal menstrual cycles received vehicle (n=9) or 0.03mg ZK137316 (n=8)/kg body weight i.m. daily for 3 months. Controlled ovarian stimulation with recombinant gonadotropins was initiated in the 3rd month. Oocytes collected from preovulatory follicles were evaluated for nuclear maturity and inseminated in vitro. Preimplantation embryonic development was monitored in vitro. The total number of oocytes and percentage collected at each nuclear stage were similar in both groups. More (P<0.05) atretic oocytes were recovered following antiprogestin relative to vehicle treatment. Fertilization rates and percentages of embryos that progressed to the morula stage were similar between groups, but antiprogestin-treated females exhibited less (P<0.05) normal cleavage. Embryonic development was accelerated by 1 day (P<0.05) from the 16-cell to the morula stage in the antiprogestin group relative to vehicle. Despite this, the majority of embryos became blastocysts within 6 days in vitro in the antiprogestin group, but fewer expanded (P=0.09) and hatched (P<0.05) compared to vehicle. During in vivo treatment with chronic, low-dose antiprogestin, oocytes retained their ability to resume and complete meiosis as well as fertilize following insemination in vitro. However, preimplantation embryogenesis in vitro was impaired, particularly during the later stages of blastocyst development. Thus, antiprogestin exposure during follicular development altered oocyte functions that are critical for normal preimplantation embryogenesis; this may contribute to pregnancy prevention.
KW - Antiprogestin
KW - Contraception
KW - Oocyte
KW - Preimplantation embryogenesis
UR - http://www.scopus.com/inward/record.url?scp=0346366915&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0346366915&partnerID=8YFLogxK
U2 - 10.1016/S0039-128X(03)00143-0
DO - 10.1016/S0039-128X(03)00143-0
M3 - Article
C2 - 14667997
AN - SCOPUS:0346366915
SN - 0039-128X
VL - 68
SP - 1041
EP - 1051
JO - Steroids
JF - Steroids
IS - 10-13
ER -