title: Role of the antiapoptotic proteins BCL2 and MCL1 in the neonatal mouse ovary.
abstract: The mammalian ovarian lifespan is determined at the time of birth through a delicate balance of oocyte survival and apoptosis as primordial follicles form, and the mechanism by which germ cells die is not understood. We hypothesized that two BCL2 family proteins, BCL2 and MCL1, may be responsible for regulating neonatal oocyte survival. Previous work has shown that BCL2 is important for germ cell survival in adult mouse ovaries, but no work has been done to examine its role at the time of birth. To elucidate the effects of BCL2 in the neonatal ovary, we examined ovaries of both Bcl2-overexpressing and knockout transgenic mice. When compared to wild-type mice, neither Bcl2 overexpression nor abrogation significantly altered ovarian histology. Another BCL2 family protein, MCL1, is expressed in human oocytes during ovarian development, suggesting a role for MCL1 in oocyte survival. To test this, we first examined the expression of MCL1 in the newborn mouse ovary. MCL1 was localized to both oocytes and somatic cells during primordial follicle formation. Subsequently, we used an in vitro organ culture system to identify a role for MCL1 in oocyte survival. We found that inhibition of MCL1 with an antibody to MCL1 in culture resulted in a reduced number of germ cells and an increase in cyst breakdown. Our data demonstrate that while BCL2 is not likely involved in perinatal oocyte survival, MCL1 may be an important regulator of the ovarian primordial follicle reserve.
authors.affiliation: Department of Biology, Syracuse University, Syracuse, NY 13244, USA.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Jones
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Pepling
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010053:Ovary / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D000906:Antibodies; D051017:Apoptosis Regulatory Proteins; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse