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Evidence for Genetic Modifiers of Ovarian Follicular Endowment and Development from Studies of Five Inbred Mouse Strains

Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Jonathan L. Tilly, Ph.D., Massachusetts General Hospital, VBK113-GYN, 55 Fruit Street, Boston, Massachusetts 02114. E-mail: jtilly{at}partners.org

Abstract

The laboratory mouse is the model of choice for genetic studies in mammals due to the availability of many genetically defined inbred strains and inbred congenic strains, as well as the ability to study the effects of over-expression (transgenics) or inactivation (knockouts) of a given gene on cells or tissues. During our studies using these technologies to uncover the importance of various genes to apoptosis in the ovary, we observed that the size of the primordial oocyte reserve was affected by mouse strain in the absence of any other genetic manipulation. To determine if genetic modifiers of oocyte endowment truly exist, herein we examined follicle numbers in one outbred (CD-1) and several inbred (129/Sv, DBA/2, C57BL/6, FVB, AKR/J) strains of mice at day 4 (neonatal) and day 42 (young adult) postpartum. In neonatal life, ovaries of AKR/J females had the lowest total number of follicles, whereas 129/Sv females possessed the highest total number of follicles (P < 0.05 for AKR/J versus 129/Sv). There were more primordial follicles in 129/Sv compared with DBA/2 (P < 0.05), C57BL/6 (P < 0.05), FVB (P < 0.05) or AKR/J (P < 0.05) females, and in CD-1 compared with AKR/J (P < 0.05) females. Although no significant strain-dependent differences in primary follicle numbers were noted, C57BL/6 females had the fewest number of small preantral follicles (P < 0.05 versus all other strains). Evaluation of ovaries at 42 days of age revealed the persistence of strain-dependent differences in early follicle growth patterns, although the total numbers of follicles were comparable. Of interest, marked strain-dependent differences in the rate of primordial follicle growth activation, as well as in the rate of follicle loss (atresia), between days 4 and 42 were observed. These results indicate that genetic modifiers play a major role in follicle endowment, development and atresia in the mouse ovary.

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