Activin Decoy Receptor ActRIIB:Fc Lowers FSH and Therapeutically Restores Oocyte Yield, Prevents Oocyte Chromosome Misalignments and Spindle Aberrations, and Increases Fertility in Midlife Female SAMP8 Mice
| Autor: | Charles L. Chaffin, Se-Jin Lee, Lori R. Bernstein, Istvan Merchenthaler, Amelia C.L. Mackenzie |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Infertility medicine.medical_specialty endocrine system Aging Litter Size Activin Receptors Type II Aneuploidy Oocyte Retrieval CHO Cells Spindle Apparatus Biology Chorionic Gonadotropin Andrology 03 medical and health sciences Follicle-stimulating hormone Mice Endocrinology Cricetulus Internal medicine Chromosome Segregation medicine Animals Advanced maternal age Horses Receptor Equine chorionic gonadotropin Original Research medicine.disease Oocyte Spindle apparatus Activins Immunoglobulin Fc Fragments Meiosis 030104 developmental biology medicine.anatomical_structure Fertility Oocytes Reproductive Control Agents Female Follicle Stimulating Hormone hormones hormone substitutes and hormone antagonists Maternal Age |
| Zdroj: | Endocrinology. 157(3) |
| ISSN: | 1945-7170 |
| Popis: | Women of advanced maternal age (AMA) (age ≥ 35) have increased rates of infertility, miscarriages, and trisomic pregnancies. Collectively these conditions are called “egg infertility.” A root cause of egg infertility is increased rates of oocyte aneuploidy with age. AMA women often have elevated endogenous FSH. Female senescence-accelerated mouse-prone-8 (SAMP8) has increased rates of oocyte spindle aberrations, diminished fertility, and rising endogenous FSH with age. We hypothesize that elevated FSH during the oocyte's FSH-responsive growth period is a cause of abnormalities in the meiotic spindle. We report that eggs from SAMP8 mice treated with equine chorionic gonadotropin (eCG) for the period of oocyte growth have increased chromosome and spindle misalignments. Activin is a molecule that raises FSH, and ActRIIB:Fc is an activin decoy receptor that binds and sequesters activin. We report that ActRIIB:Fc treatment of midlife SAMP8 mice for the duration of oocyte growth lowers FSH, prevents egg chromosome and spindle misalignments, and increases litter sizes. AMA patients can also have poor responsiveness to FSH stimulation. We report that although eCG lowers yields of viable oocytes, ActRIIB:Fc increases yields of viable oocytes. ActRIIB:Fc and eCG cotreatment markedly reduces yields of viable oocytes. These data are consistent with the hypothesis that elevated FSH contributes to egg aneuploidy, declining fertility, and poor ovarian response and that ActRIIB:Fc can prevent egg aneuploidy, increase fertility, and improve ovarian response. Future studies will continue to examine whether ActRIIB:Fc works via FSH and/or other pathways and whether ActRIIB:Fc can prevent aneuploidy, increase fertility, and improve stimulation responsiveness in AMA women. |
| Databáze: | OpenAIRE |
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