Oocyte Survival and Development during Follicle Formation and Folliculogenesis in Mice Lacking Aromatase

ABSTRACT

Background

Assembly of oocytes into primordial follicles is essential for establishing the ovarian reserve required for female fertility. In mice, this process begins during embryonic development. Primordial germ cells form cysts by incomplete mitosis until 13.5 days post coitum (dpc). These cysts break apart just before birth. Some oocytes undergo apoptosis while surviving oocytes are enclosed by granulosa cells to form primordial follicles. Cyst breakdown and primordial follicle formation were previously shown to be inhibited by estradiol and estrogenic compounds in vitro, suggesting that estrogen is important for regulation of this process.

Methods

To determine the role of fetal estrogen in cyst breakdown and follicle formation these processes were quantified in aromatase deficient (ArKO) mice between 17.5 dpc and postnatal day (PND) 9. Ovaries of ArKO mice were also examined at 2-week intervals to determine if folliculogenesis is affected by lack of estrogen and the age at which the typical ArKO ovarian phenotype first appears.

Results

Oocyte number, follicle assembly, and follicle development in ArKO mice did not differ from controls between 17.5 dpc and PND 9. At 2 weeks, ArKO ovaries still had oocytes in cysts while all oocytes were enclosed in follicles in wild type ovaries. From 2 to 8 weeks oocyte numbers were similar in all genotypes with a significant reduction at 10 weeks in ovaries from homozygous mutants. Abnormal hemorrhagic follicles were observed starting at 6 weeks, earlier than previously reported and hemosiderin deposits were found starting at 8 weeks.

Conclusions

These results suggest that a lack of fetal estrogen does not affect oocyte survival or the rate of primordial follicle formation perinatally, and maternal estrogen or other signals are the chief regulators. The appearance of abnormal hemorrhagic follicles observed as early as 6 weeks suggests that the lack of estrogen becomes problematic at this time.

KEYWORDS:

• Aromatase
• follicle development
• steroid hormone biosynthesis
• oocyte survival

Data availability statement

Data available on request from the authors.

Acknowledgments

The authors thank members of the Pepling lab for critical review of the manuscript, Orhan Oz for providing ArKO mice and Ned Place for assistance with histology.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported in part by a grant from the National Science Foundation NSF IOS-1146940</#AWARD-ID;> (to MEP).