573-882-6798
440F Life Sciences Center
University of Missouri
Columbia, MO 65211
Lab Information:
445 Life Sciences Center
573-882-5132
Members—Angela M. Davis, Dr. Jaime
Riley, Dr. Jeff Whyte
Research Interests: My
research focuses on two main areas.
1) I am interested in studying the putative
therapeutic effects of type I IFN on treating
human endometrial cancers. Past studies
have suggested that type I IFN, such as
IFN-a and IFN-b, in combination with anti-estrogens
might hold greater promise for treating
estrogen-responsive tumors. The underlying
mechanism might be that they up-regulate
ER, and thereby, IFN make the tumors more
sensitive to anti-estrogens, such as tamoxifen
and raloxifene. My NIH funded study examines
the effects that IFN-a and raloxifene have
on various human endometrial cancer cells.
As part of these studies, we will also examine
the effects that type I IFN have on normal
uterine ER expression. By using a microarray
approach, we will further examine the effects
of IFN on estrogen-responsive genes.
2) My second area of interest involves
studying the effects that maternal diet
has on offspring sex ratio. This research
was initiated in order to determine how
the sex of offspring can be influenced by
the diet consumed by the mother. There is
evidence to suggest that in several mammals,
including humans, mothers on restricted
calorie intake produce daughters more frequently
than sons (see below). In contrast energy-rich
diets may favor sons. Our hypothesis is
that diet, either directly or indirectly
(e.g. through hormonal changes in the mother),
influences the nutrient conditions within
the reproductive tract of an early pregnant
female. These changes in turn could alter
the relative abilities of either X- or Y-sperm
to effect fertilization. Alternatively,
an altered uterine environment might lead
to preferential survival of embryos of one
sex over the other. Such sex allocation
might have adaptive significance, allowing
a mother to produce offspring that provide
her with the best opportunity of passing
her genes on to future generations under
a prevailing set of environmental conditions.
We have established that in the mouse, a
litter-bearing, polygonous species, mothers
fed a diet high in lard produce significantly
more sons than daughters, whereas mothers
on a low fat, high carbohydrate, produce
more daughters than sons. Experiments are
underway to understand the mechanisms involved
and whether a similar phenomenon occurs
in sheep. An ability to manipulate sex of
offspring through diet has potentially important
application in the livestock industry.
Teaching: BMS 5502 and
5503 Veterinary Microanatomy
BMS 5508 Veterinary Pharmacology (Reproductive
Pharmacology lectures in this course)
Selected Publications:
Rosenfeld CS, Murray AM, Simmer G, Hufford
MG, Smith MF, Spears N, Lubahn DB Gonadotropin
Induction of Ovulation and Corpus Luteum
Formation in Young Estrogen Receptor-a Knockout
MIce. Biol Reprod 2000; 62:599-605.
Yellayi S, Teuscher C, Woods J, Welsh TH
Jr, Tung KSK, Nakai M, Rosenfeld CS, Lubahn
DB, Cooke PS Normal development of thymus
in male and female mice requires estrogen/estrogen
receptor-a signaling pathway. Endocrine
2000; 12:207-213.
Rosenfeld CS, Cooke PS, Welsh TH, Simmer
G, Hufford MG, Hess RA, Lubahn DB The differential
fate of the mesonephric tubular-derived
efferent ductules in estrogen receptor-a
knockout versus wild-type female mice. Endocrinology
2000; 141:3792-3798.
Schatten H, Wiedemeier AM, Taylor M, Lubahn
DB, Greenberg NM, Besch-Williford, Rosenfeld
CS, Day JK, Ripple M. Centrosome-centriole
abnormalities are markers for abnormal cell
divisions and cancer in the transgenic adenocarcinoma
mouse prostate (TRAMP) model. Biol Cell
2000; 92:331-340.
Chen X, Rosenfeld CS, Roberts RM, Green
JA. An aspartic proteinase expressed in
the yolk sac and neonatal stomach of the
mouse. Biol Reprod 2001; 65:1092-1101.
Rosenfeld CS, Roberts RM, Lubahn DB. Estrogen
receptor and aromatase deficient mice provide
insight into the roles of estrogen within
the ovary and uterus. Molecul Reprod Develop
2001; 59:336-346.
Rosenfeld CS, Roberts RM, Lubahn DB. Intraovarian
actions of oestrogen. Reproduction 2001;
122:215-226.
Manikkam M, Bao B, Rosenfeld CS, Yuan X,
Salfen BE, Calder MD, Youngquist RS, Keisler
DH, Lubahn DB, Garverick HA. Expression
of the bovine oestrogen receptor-b (bERb)
messenger ribonucleic acid (mRNA) during
the first ovarian follicular wave and lack
of change in the expression of bERb mRNA
of second wave follicles after LH infusion
in cows. Anim Reprod Sci 2001; 67:159-169.
Rosenfeld CS, Han C-S, Alexenko AA, Spencer
TE, Roberts RM. Expression of interferon
receptor subunits, IFNAR1 and IFNAR2, in
the ovine uterus. Biol Reprod 2002; 67:
847-853.
Akingbemi BT, Ge R, Rosenfeld CS, Newton
LG, Hardy DO, Catterall JF, Lubahn DB, Korach
KS, Hardy MP. Estrogen receptor-a gene deficiency
enhances androgen biosynthesis in the mouse
Leydig cell. Endocrinology 2003; 144:84-93.
Roberts RM, Ezashi T, Rosenfeld CS, Kubish
HM. The interferon-t: evolution of the genes
and their promoters, and maternal- trophoblast
interactions in control of their expression.
2003; Reproduction 61:239-251.
Rosenfeld CS, Grimm KM, Livingston KA,
Brokman AM, Lamberson WR, Roberts RM. Interaction
between maternal diet and sex ratio of offspring,
Proc Natl Acad Sci. USA. 2003; 100:4628-4632.
Cheryl
S. Rosenfeld, PhD, DVM