Maternal tamoxifen treatment alters oocyte differentiation in the neonatal mice: inhibition of oocyte development and decreased folliculogenesis

Abstract

Aim: Primary germ cells after migration to the developing ovary differentiate to oogonia and oocytes. The formation and number of primordial follicles in early fetal life are determining factors in the fertility state of adult life. Tamoxifen is used both to stimulate ovulation and as an anticancer drug. The aim of the present study was to evaluate the effect of tamoxifen on oocyte and follicular development and differentiation in mice.

Methods: Thirty adult female and 15 adult male mice were used in the present study. The female mice were divided into two groups: control and experimental. Two female mice at their sterous cycle were placed with one male mouse in a cage for mating. The observation of a vaginal plug was considered the 1st day of pregnancy. On the 13th day of pregnancy the mice received 100 microg tamoxifen by i.p. injection. At the end of pregnancy 2-, 3-, 6- and 7-day-old newborns were killed and their ovaries were fixed and prepared for light and electron microscopic studies. The number of follicular nests and diameter of primordial and primary follicles were determined using Motic software (Motic Incorporation Ltd, Canada) and compared with control values using t-test.

Results: Microscopy and morphometry showed that oocyte nests are formed on the 2nd and 3rd days and follicles are distinguished on the 6th and 7th days. Morphometric studies revealed that the number and diameters of oocyte nests were significantly (P < 0.001) reduced in the experimental groups compared to the control group. However, the numbers and diameters of primordial and primary follicles in experiential and controls were not significantly different. Electron microscopic studies revealed that in the control group, oocytes were separated from each other and were at primordial follicle stage. However, in the experimental group, the oocytes were in clusters as oocyte nests.

Conclusion: The results indicate that tamoxifen suppresses follicular differentiation at early stages but does not affect the development of already differentiated follicles.