Faculty and Research
Melissa E. Pepling
Associate Professor
mepeplin@syr.edu
Office: LSC 348
Phone: 315-443-4541; Lab: 315-443-9948
Lab website
Research Program Overview
The pool of primordial follicles present at birth represents the
total population of germ cells available to a female during her entire
reproductive life. Establishment of this source of oocytes is absolutely
essential for fertility. Shortly after forming, female germ cells
undergo a series of incomplete cell divisions resulting in clusters
called cysts. Just after birth, mouse germ cell cysts break down
into individual oocytes (cyst breakdown) that are surrounded by pre-granulosa
cells to form primordial follicles. During cyst breakdown, a subset
of oocytes in each cyst dies by programmed cell death with only a
third of the initial number of oocytes surviving. The long-term goal
of our research is to understand the mechanisms that regulate cyst
breakdown and programmed cell death to establish the primordial follicle
pool in the mouse ovary.
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For more details about my research and related publications,
please select from the following:
Hormone signaling in regulation of oocyte development
Programmed cell death regulators in oocyte differentiation |
Undergraduate Research Opportunities
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:
Germline Cyst Formation and Development in Zebrafish - Tess Cherlin, BS 11
The Effect of Exogenous Estrogens on Primordial Follicle Assembly in vivo - Jenna Karavan, BS 10
The Role of Fragile X Mental Retardation Protein in Neonatal Oocyte Development - MaryAnn Danosos, BS 09
The Role of Estrogen Receptor Alpha in Neonatal Oocyte Development - Jemella Raymore, BS 08
Estrogen Receptor Beta in Neonatal Oocyte Development -
Kelsey Breen, BS 07
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.
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