The Research Focus of the Cupp laboratory is to study the molecular and cellular regulators of gonadal development and function. Primarily, our laboratory is investigating a paracrine growth factor- Vascular Endothelial Growth Factor (VEGF) and its involvement in: 1) sex-specific vascular development during embryonic gonadal development; 2) follicular maturation; and 3) ovulation in the female and; 4) its role in spermatogenesis.\

Vascular Endothelial Growth Factor (VEGFA)

Early Gonadal Development: The reason that we are studying early development of structures (follicles, vasculature and seminiferous cords) in the testis and ovary is that many causes of adult and potentially domestic livestock infertility can be traced back to abnormal cellular differentiation during gonadal development. For example, in the past twelve years there has been an increase in male infertility cases in several Industrialized Countries (including the US). These men are infertile due to several different reasons from testicular cancer (increased incidence in men under 20 years of age) to low sperm count. Most of these cases can be attributed to potential abnormal differentiation of cells during development of the embryonic or fetal testis.

We have two projects one in the ovary and the other in the testis which are studying the regulation of angiogenic factors during ovarian or testicular embryonic differentiation.

1) Role of angiogenic factors in morphological testis differentiation.

Development of the initial cellular structures that constitute a testis occurs during embryonic development. Formation of the testicular cords (or seminiferous cords) is the first visual indication that the gonad is a testis. During the differentiation of an indifferent (non-differentiated) gonad into a testis sex-specific vasculature develops around the seminiferous cords in a pattern different from vascular development in the ovary.

 

In this project we are studying how vasculature formation affects testis morphogenesis or formation of seminiferous cords. We use both rat and mouse models in our research. Currently, we have data demonstrating that VEGFA is involved in Seminiferous cord formation and sex-specific vascular development. Either inhibition of VEGF or additional of large amounts of VEGF isoforms both arrest seminiferous cord formation and affect vascular density (inhibition of VEGF reduces vascular density while addition of angiogenic isoforms increases vascular density). We believe that absence of VEGFA inhibitory isoforms and presence of angiogenic isoforms may aid in endothelial cell migration and development of sex-specific vasculature and testis cord formation. This project is funded by a grant from NIH.

2) Role of angiogenic factors in morphological ovarian differentiation (ie- sex-specific vascular develoment and primordial follicle formation).

In this project we are studying the role of Angiogenic factors in the formation of vasculature and primordial follicle development the embryonic and postnatal rat & mouse ovary. In addition to evaluation of VEGF. Portions of this project were funded by Women in Science Grant from NSF-Epscore.

3) Identification of growth factors involved in follicle progression and ovulation.

We are utilizing the cow as a model system to identify paracrine growth factors involved in the process of follicle maturation and ovulation in the beef cow. The beef cow is an excellent model for humans since the cow is mono-ovulatory, the ovary is similar in size to women's ovaries and the pattern of endocrine hormones is also very similar. In this project we are trying to understand the mechanisms of ovulation by identifying paracrine growth factors, both angiogenic and non-angiogenic which are induced during the process of ovulation. By identifying these factors we hope to improve synchronization of ovulation which would lead to more efficient estrous synchronization and improved IVF techniques. This project is funded through state and regional USDA Hatch & Animal Health Funds.

4) Applied Research to development management practices to increase male or female reproductive efficiency and fertility in cattle.

a) Use of different supplements and feed additives during heifer development to determine effects on reproductive performance

-this research is conducted in collaboration with Dr. Rick Funston at West Central Research and Extension Center at North Platte, NE.

1) Dried Distillers grains

2) Whole soybeans

b) Use of synthetic progestins (MGA), progesterone (CIDRS), male biostimulation (bull exposure), etc to determine effects on conception rate to AI, testis characteristics during male puberty, oocyte (egg) competence and fertilizability.

 

- this research is conducted mainly in my lab but we have some great collaborators- Bob Cushman (USMARC), Brett White (UNL), Jennifer Wood (UNL), and Lane Christenson (UKMC) that are working with us on the effect of level of progesterone on oocyte competence and fertility project.

Bob Cushman searching for oocytes---------Brett White searching for oocytes and a come-back to Bob's comments.

We take our research as seriously as the food we eat. . . sometimes our birthday cakes and going away cakes even look like our research. . . .

 

Ovary cake (red=vasculature) green (basement membrane); Ovary girls- Robin, Robyn and Natalie.

Gonad cake- Yum Yum!! As you can see our artistic abilities go farther than gonadal dissection!! Robin and Becky--have burned the midnight oil on their masterpiece.