1. Name: Rosalina Villalon Landeros
Email: villalonland@wisc.edu
Major Professor: R Magness
Degree Objective: Endocrinology and Reproductive Physiology
Background: B.S in Neurobiology, physiology and behavior
Current Research Project: Role of Estradiol-17β and its Metabolites in Vascular
Endothelial Function in an Ovine Model of Unilateral Pregnancy
Uterine artery endothelial cells (UAECs) play a central role in the mechanisms
underlying uterine vascular adaptations, including angiogenesis and vasodilatation,
which are necessary to increase uterine blood flow (UBF) during normal pregnancy.
Inadequate maternal-fetal circulation as a result of aberrant utero-placental vascular
adaptations results in decreased fetal growth and ultimately in intrauterine growth
restriction (IUGR). Our laboratory has developed a unique ovine surgical-induced
unilateral pregnancy model. We found that in this model, uterine arteries ipsilateral to
the gravid horn undergo substantial remodeling compared to contralateral arteries. For
example uterine arteries ipsilateral to the gravid horn have a substantial increase in
blood flow, larger diameters, and higher expression of endothelial Nitric oxide synthase
(eNOS) compared to contralateral arteries. We have also demonstrated that estradiol
(E2β) and its metabolites, the catecholestradiols 2OHE2 and 4OHE2 and the
methoxyestradiols 2ME2 and 4ME2 regulate uterine artery function during normal
pregnancy by increasing UAEC proliferation and prostacyclin production, resulting in
increased angiogenesis and vasodilatation. It is unknown if the changes in UBF and
eNOS in the unilateral pregnant animals are a result of specific programming of uterine
artery endothelium to the local gravid environment. We hypothesize that UAECs
isolated from uterine arteries ipsilateral to the gravid horn [(Gravid)P-UAECs] will exhibit
pregnancy-specific programming (increased angiogenesis and vasodilator production
compared nonpregnancy), while UAECs isolated from uterine arteries contralateral to
the gravid horn [(NonGravid)P-UAECs] will not exhibit pregnancy-specific programing
(lower angiogenesis and vasodilator production compared to pregnancy). (Gravid)P-
UAECs, (NonGravid)P-UAECs, and P-UAECs NP-UAECs, previously isolated and
validated from healthy ewes with or without uterine surgical modification will be used.
Methods Differences in programming of UAECs ipsilateral and contralateral to the
gravid horn will be determined by examining angiogenesis (through proliferation assays)
2. and vasodilator production (through ELISAs and HPLC) stimulated by E2β and its
metabolites and in comparison to normal and nonpregnancy. Results: As expected, E2β
at all doses induced higher proliferation in (Gravid)P-UAECs compared to (Non-
Gravid)P-UAECs within each treatment dose. 2OHE2 and 4OHE2 followed a similar
pattern as E2β, however not all doses induced significant proliferation of (Gravid)P-
UAECs compared to (Non-Gravid)P-UAECs. 2ME2 elevated proliferation of (Gravid)P-
UAECs only at the highest dose, which was also significantly different compared to
(Non-Gravid)P-UAECs. 4-ME2 stimulated higher proliferation of (Gravid)P-UAECs
compared to (Non-Gravid)P-UAECs, but only at the highest dose was significantly
different compared to (Non-Gravid)P-UAECs. Preliminary studies assessing stimulation
of NO production in (Gravid)P-UAECs indicate that 4OHE2 and 2ME2 increased
production of NO after 10 minutes of treatment. In conclusion, our data indicate there is
differential programming of the (Gravid)P-UAECs and (Non-Gravid)P-UAECs, where the
(Gravid)P-UAECs display similar programing as normal P-UAECs as indicated by their
increased proliferative and possibly NO production response to E2β and its metabolites.
In contrast (Non-Gravid)P-UAECs programming appears to be similar to the NP-UAECs
as demonstrated by their lack of proliferative response to E2β and its metabolites.
Grants Received:
2015-2018 NIH, Ruth L. Kirschstein National Research Service Award Individual
Predoctoral Fellowship to Promote Diversity in Health-Related Research
(Parent F31 - Diversity) 1F31HD088096-01 (Award Pending)
2012- 2014 NIH, National Institute of General Medical Sciences. R25 GM083252,
TEAM Science. PI: Molly Carnes. Trainer, Ronald R. Magness.
Honors:
Nominated by Dean Dr. VandenBosch to participate in the AAAS/Science
Program for Excellence in Science, and awarded a two- year membership to
AAAS. Spring 2015
Recipient of the Burroughs Welcome Travel Fellowship. 2013 Society for the
study of Reproduction.
Recipient of “Best New Investigator Poster Presentation” award. 2013 Society for
Gynecologic Investigation annual meeting.
3. The Endocrine Society’s Poster Presentation Award at the Society for the
Advancement of Chicanos and Native American’s in Science, National
Conference in Anaheim, CA. 2010
Publications:
1. Trish Berger, Valerie Guerrero, Rosalina Villalon Landeros, Erin Legacki,
Megan Roberts, Alan J Conley. Development of Porcine Accessory Sex Glands.
Journal of Endocrinology. Submitted for publication, Jan 2016
2. Laredo SA, Villalon Landeros R, Trainor BC. Rapid effects of estrogens on
behavior: environmental modulation and molecular mechanisms. Front
Neuroendocrinol. 2014. pii: S0091-3022(14)00039-9
3. Pastore, M., Villalon, R., López, G., Iruretagoyena, J. y Magness, R. R.
Regulación del Flujo Sanguíneo Uterino. II. Funciones de Estrógeno y
Receptores Estrogénicos α/β en las acciones Genómicas y No-genómicas del
Endotelio Uterino. Rev Chil Obstet Ginecol. 2014; 79(3): 218-228.
4. Pastore, M., Villalon, R., López, G., Iruretagoyena, J. y Magness, R. R. “Regulación
del Flujo Sanguíneo Uterino. I. Funciones de Estrógeno y Receptores Estrogénicos
α/β en el Endotelio Vascular Uterino durante el Embarazo.” Rev Chil Obstet
Ginecol. 2014, 79(2): 129-139.
5. Laredo S.A., Landeros R.V., Dooley JC.., Steinman M.Q., Orr V. Silva A.L.,
Crean K.K., Robles C.F., Trainor B.C. (2013). Nongenomic effects if estradiol on
aggression under short day photoperiods. Hormones and Behavior. 64(3):557-
565.
6. Kao E, Villalon R, Ribeiro S, Berger T. (2012) Role for endogenous estrogen in
prepubertal Sertoli cell maturation. Anim Reprod Sci. 35(1-4):106-12.
7. Villalon Landeros R, Morisseau C, Yoo HJ, Fu SH, Hammock BD, Trainor BC.
2012. Corncob bedding alters the effects of estrogens on aggressive behavior
and reduces estrogen receptor alpha expression in the brain. Endocrinology.
153(2):949-53.
8. Trainor BC, Pride MC, Villalon Landeros R, Knoblauch NW, Takahashi
EY, Silva AL, Crean KK. (2011). Sex differences in social interaction behavior
following social defeat stress in the monogamous California mouse (Peromyscus
californicus). PLoS ONE, 6, e17405.
4. National Presentations:
Oral Presentations:
Rosalina Villalon Landeros, S. Omar Jobe, Jing Zheng, Ronald R. Magness. 4-
(2015). Methoxyestradiol Induces Proliferation through a Gαi Protein Coupled
Receptor-Dependent Mechanism in Uterine Artery Endothelial Cells Derived from
Pregnant Ewes. March 2015, Society for Reproductive Investigation.
Poster Presentations:
Rosalina Villalon Landeros, Mayra B. Pastore, Chariesse A. Ellis, Gladys E. Lopez,
Ronald R. Magness. Catecholestradiols and Metoxyestradiols Stimulate Pregnancy
Specific Nitric Oxide Production in Uterine Artery Endothelial Cells. Accepted for poster
presentation at the Society for Reproductive investigation annual meeting. March 16-19
2016. Montreal Canada.
Rosalina Villalon Landeros, Mayra B. Pastore, Chariesse A. Ellis, Gladys E. Lopez,
Ronald R Magness. (2015). Endothelial Cell Nitric Oxide Production Induced by Estradiol
Metabolites. Summer 2015. At Endocrinology and Reproductive Physiology Program
Symposium.
Rosalina Villalon Landeros, S. Omar Jobe, Gladys E. Lopez, Jing Zheng,
Ronald R Magness. (2014) O-Methylated Metabolites of Catecholestrogens and
Catecholamines Induce Similar Angiogenic Responses in Uterine Artery
Endothelial Cells Derived from Pregnant Sheep. Society for the Study of
Reproduction annual meeting: June 2014, Grand Rapids, Michigan.
Rosalina Villalon Landeros, SO Jobe, J Zheng, RR Magness. (2013) 4-
Methoxyestradiol Induced Proliferation of Uterine Artery Endothelial Cells Occurs
via Activation of p38, p42/44 and JNK MAPKs and Independent of Estrogen and
Adrenergic Receptors. Society Gynecologic Investigation: March 2013, Orlando,
Florida.
Other Presentations:
Rosalina Villalon Landeros, S. Omar Jobe, Mayra B. Pastore, and Ronald R.
Magness (2013) Ovine Uterine Artery Endothelial Cell ER-α, ER-β, and GPR30
Expression during the Luteal Phase, Follicular Phase, and Pregnancy. SSR: July
2013. Montréal, Québec, Canada (Poster Presentation)
5. Teaching and Mentorship:
Mentor Dr. Watanabe, visiting scientist, on basic research methods and data
analysis including. Cell culturing, performance and analysis of protein assays and
Elisa assay, western blotting and other techniques. December 2015- May 2016
Mentor Gabrielle Aranda-Pine, undergraduate student. Mentorship, protein assay
western blotting and proliferation assays. Fall 2015- current
Mentor Chariesse Ellis, undergraduate student, member of the undergraduate
student research program (USR). Mentorship in cell culture, Elisa assays,
western blotting and proliferation assays. Fall 2014- Spring 2015
Mentored Keona Thompson, undergraduate student from the RUSCH summer
program. Mentorship in endothelial cell culture, proliferation assays and western
blotting. Summer 2013
ERP Service:
Endocrinology and Reproductive Physiology Program. University of Wisconsin-
Madison. Program Retreat planning committee member. Fall 2014- on going
Obstetrics and Gynecology Department Chester B. Martin MD Graduate Training
Program Mentorship Award. Committee member. Spring 2015
Endocrinology and Reproductive Physiology Program. University of Wisconsin-
Madison. Annual Research Symposium planning committee member. Spring
2014-on going
Society for The study of Reproduction Minority Affairs. Student committee
member ERP Retreat planning committee. 2013- 2014