Effect of vitamin d and ulipristal acetate in the ovarium stimulated by estrogen-progesterone complex

Folliculogenesis is a complex process that occurs in the ovaries, with various growth factors and signal molecules take part. One of the hormones involved in the control of ovulation is progesterone. Recent studies show that progesterone stimulates ovulation and primary follicle development. High progesterone concentration suppresses ovulation and secondary follicle development. In the light of this information, it can be deduced that Ulipristal acetate (UPA) as a progesterone receptor modulator has a role in folliculogenesis. There are limited studies about the effect of UPA on folliculogenesis. Vitamin D3 is another factor that has been shown to play an important role in ovarian functions including follicular development. VitD3 supplementation increases preantral follicle survival, antral follicle growth, and survival. It has been shown that VitD3 also regulates steroidogenesis by stimulating progesterone and estradiol synthesis in the ovary. Research on follicular development mechanisms will provide more comprehensive data on female reproductive life and the development of new therapeutic approaches against reproductive aging. In this respect, it is important to understand the effect mechanism in folliculogenesis of UPA and VitD3, which are increasingly used together in recent years for antifibroid effects in uterine fibroid treatment. In our study, we investigated the effects of UPA and VitD3 on folliculogenesis by used histochemical methods in a rat model. In study 48 female Wistar-albino rats randomly divided into seven groups: control group, 3 weeks oral VitD3 (300 ng/day) administration group, 5 weeks oral UPA (3 mg/kg/day) administration group, every 2 days for 5 weeks oral DES (1,35 mg/kg/day) and IM progesterone (1mg/kg) administration group, after DES and progesterone administration 3 weeks oral VitD3 (300 ng/day) treatment group, 5 weeks oral UPA (3 mg/kg/day) treatment group, VitD3+UPA treatment group. Follicles in normal stages have become atretic and hemorrhagic cystic structures were observed in the UPA group. In the high estrogen–progesterone administration group, the granulosa cell layers of antral follicles were determined to be relatively thin like the polycystic ovary syndrome. Giant follicles with thinning walls were also observed in the UPA and VitD3+UPA treatment groups. In the high estrogen–progesterone applied group, many corpus luteums were detected due to an increase at LH peak and ovulation caused by estrogen. Corpus luteum degeneration was also observed before maturation because of negative inhibition of progesterone. The structure of the corpus luteum was normal in the VitD3 treatment group. We demonstrated that; UPA prevented progesterone negative feedback, and corpus luteums were observed to be enlarged in the UPA treatment group. UPA and VitD3 cause excessive vascular dilatation and congestion. As a result, it was observed that VitD3 and VitD3+UPA treatment groups gave the best results in terms of folliculogenesis in the condition of high estrogen–progesterone.