PARENT SESSION
Oocyte Development
85
THE EFFECTS OF SHP-1 DEFICIENCY ON MOUSE OVARIAN FOLLICLE DEVELOPMENT.
Papademetriou, Suzanne1,3, Kozlowski, Maya1,2, Vanderhyden, Barbara1,3, 1 3 2
ABSTRACT- The SHP-1 phosphatase is widely recognized for its role in regulating the activity of many receptor and non-receptor tyrosine kinases. We have investigated its role in the mouse ovary and indirectly its ability to inhibit the activity of the receptor tyrosine kinase Kit. Kit is expressed in oocytes and is involved in primordial germ cell (PGC) proliferation and oocyte growth. We have observed SHP-1 expression in all ovarian cell types throughout follicle development. To investigate the involvement of SHP-1 in regulating PGC proliferation and oocyte growth we examined the phenotype of SHP-1 deficient motheaten (me) mice. The mass of ovaries from 11-13 day old me/me mice (135±13 
g) was 48% less than that of age-matched wildtype (wt) animals (281±31 g). Me/me mice showed a 36% increase in the total number of oocytes per ovary relative to wt animals, suggesting that the lack of SHP-1 may impact on the proliferation of PGC and consequent size of the neonatal pool of oocytes. There was no difference in the total number of growing follicles in me/me vs. wt mice, nor was there any difference in the distribution of size of growing oocytes. However, there were significantly fewer growing follicles that had ≥4 layers of granulosa cells, suggesting that SHP-1 may regulate granulosa cell proliferation. In wt mice, SHP-1 protein expression, as shown by western blot analysis, was greater in fully grown oocytes compared with growing oocytes suggesting a role for SHP-1 in regulating the termination of oocyte growth. Since me/me mice die before 3 weeks of age and we wanted to examine oocyte growth, ovaries were obtained from 10-12 d.o. me/me mice as well as age-matched controls and were transplanted under the kidney capsule of SCID mice and left for 8-10 days. Ovaries were then fixed, paraffin-embedded and sectioned for histological analysis. Both wt and me/me ovaries were able to form large antral follicles in similar proportions. Interestingly, me/me oocytes (55.03±2.1m) achieved larger sizes than wt oocytes (45.2±1.5m). Taken together, these results suggest that SHP-1 may interact with Kit to regulate PGC proliferation and oocyte growth, however, the loss of SHP-1 does not impair granulosa cell proliferation and follicle development.
KEY WORDS: oocyte growth, ovary transplantation, Kit tyrosine kinase, SHP-1 phosphatase