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.
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.
BS, DVM—University of Illinois
PhD—University of Missouri-Columbia
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.