ALTERATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR A (VEGFA) ISOFORM EXPRESSION RESULTS IN ABNORMAL GONADAL FUNCTION

Authors

Ningxia Lu, University of Nebraska-LincolnFollow

Date of this Version

11-2010

Document Type

Article

Comments

A THESIS Presented to the Faculty of The Graduate College at the University of Nebraska In Partial Fulfillments of Requirements For the Degree of Master of Science, Major: Animal Science, Under the Supervision of Professor Andrea S. Cupp. Lincoln, Nebraska: November, 2010
Copyright 2010 Ningxia Lu

Abstract

In the female, vascular endothelial growth factor A (VEGFA) isoforms regulate follicle development and affect the initial primordial follicle pool. In male rodent testes, they are involved in the development of vasculature and seminiferous cords. The objective of the current study was to evaluate effects of Sertoli and Granulosa cellspecific production of VEGFA isoforms on vascular development and gonadal morphogenesis. We used a DMRT1-cre crossed to a floxed VEGFA mouse to determine potential phenotypes in male Sertoli-cell (VEGFA-DSertG) and female Granulosa-cell (VEGFA-DGranG) specific knockouts. In females, we found smaller ovarian weight, fewer corpus luteums (CLs) with some abnormal CL morphology, and 55% reduction in estrogen in the VEGFA-DGranG compared to controls. The number of days mated until parturition was 12 days longer in VEGFA-DGranG X VEGFA-DSertG pairs versus control females mating with control males. In males, the weight of body, testes and epididymides in VEGFA-DSertG mice were significantly reduced than those from the controls. The morphology of epididymis and prostate appeared to be different with less tubules and branching, respectively compared to controls. Serum testosterone levels in VEGFA-DSertG tended to be higher than those in controls. Bcl-2 mRNA and Bcl-2/Bax in VEGFA-DSertG testis tended to be higher than that in controls. Sin3a mRNA within testis was higher in those three VEGFA-DSertG males with high serum testosterone concentration than controls. Therefore, we conclude that lack of VEGFA in Granulosa and Sertoli cells alters reproductive organ morphogenesis, reduces gonadal and male accessory gland organ weights, alters steroidogenesis and creates sub-fertility in mice.