u n d e r g r a d u a t e . r e s e a r c h.. o p p o r t u n i t i e s

The development of germ cells (eggs and sperm) is necessary to ensure the survival of future generations.  The pool of primordial follicles present at birth represents the total population of eggs or oocytes available to a female during her entire reproductive life.  Establishment of this source of oocytes is absolutely essential for fertility.  The basic mechanisms underlying normal oocyte development as well how disorders disrupt these normal processes are not well understood.  In order to gain insight into early oocyte development in mammals, we are studying this process in normal mice and in several different genetic strains of mice in which female fertility is reduced

Students who join the lab will design a research project that combines both the student's area of interest and ongoing research in our lab. Because of the time required to read and study the literature, develop a research question, and perform the research, students should anticipate the project taking at least 1.5 - 2 years.  A minimum of 10 hours per week spent in the lab is expected.

Past research projects:

The Role of Estrogen Receptor Beta in Neonatal Oocyte Development - Kelsey Breen, BS 07
Previous studies have focused on the treatment of neonatal mice with estrogenic compounds and the effect this has in the adult ovary.  Estrogen signals are received by two receptors: Estrogen receptor alpha (ERα) and Estrogen receptor beta (ERβ).   The purpose of this project was to try to understand the role of estrogen signaling through ERβ in the neonatal ovary.   Mutant mice lacking ERβ were obtained and examined for defects in cyst breakdown, germ cell death and follicle development.  Ovaries were gathered from neonates during cyst breakdown of wild type B6 control (+/+), and ER heterozygous (+/-) and homozygous mutant knockout mice (-/-).  ERβ knockout mice exhibited no detrimental effect in cyst breakdown or total oocyte numbers.  Follicle development results were inconclusive and further analysis is necessary.  These data add to the understanding of mechanisms of cyst breakdown.  Ultimately, we hope this will provide a better understanding of oocyte development.

Analysis of a Gene Trap Insertion in the Mouse trailerhitch Gene - Ashley O'Hara, BS 06
The Drosophila Trailerhitch protein was identified as a member of a large complex of proteins that localizes mRNAs to the oocyte, a process critical for oocyte development and fertility.  Antibodies against the Drosophila Trailerhitch protein showed that this protein was present in oocytes.  The Drosophila Trailerhitch antibody was also tested on neonatal mouse ovaries and labeled oocytes, suggesting the existence of a mouse homolog of the trailerhitch gene.  To investigate the function of the mouse trailerhitch gene, a targeted disruption of this gene was generated using a gene trap approach.   We found that trailerhitch homozygous mutants are embryonic lethal before 9.5 days poitcoitum (dpc).  Using a b-galactosidase reporter we find that Trailerhitch is ubiquitously expressed at 13.5 dpc. These results suggest a role for trailerhitch in embryonic development perhaps in RNA transport or metabolism.

The Role of Dax1 in Early Mouse Oogenesis- Krystal Wilson, BS 05
Dax1 encodes a transcription factor that has been implicated in sex determination and gonad differentiation. Mice lacking the Dax-1 gene exhibit an abnormal multiple oocyte follicle phenotype.  These multiple oocyte follicles may be cysts that never completed the cyst breakdown process. Ovaries from animals lacking Dax-1 had reduced cyst breakdown and reduced oocyte survival.  In addition, expression of Dax-1 was examined in normal mice and Dax-1 was found to be present during the cyst breakdown period.

The Role of FMR1 in Early Mouse Oogenesis- Luis Carvajal, BS 04
Mutations in the FMR1 gene cause fragile X syndrome, a form of mental retardation in humans. FMR1 encodes a protein with an RNA binding motif. The FMR1 knockout mouse resembles the human disease phenotype with deficits learning and memory. In addition, like the human patients, the males have macroorchidism caused by increased perinatal Sertoli cell proliferation. In females, FMR-1 mRNA is found in oogonia and oocytes in the fetal ovary. Although the FMR-1 knockout females are fertile, the expression of FMR-1 in oocytes suggests that FMR-1 may play some as yet unidentified role in oocyte differentiation.

Melissa Pepling
806 BRL
443-4541
mepeplin@syr.edu