Evaluation of Pinopodes Expression on the Mouse Endometrium Immediately before Implantation by Treatment with HMG/HCG and Sildenafil Citrate Administration

Document Type: Original Article

Authors

1 Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran

2 Departments of Anatomy and Histology, School of Medicine, Tabriz University of Medical Science, Tabriz, Iran

3 Drugs Applied Research Centre, Tabriz University of Medical Science, Tabriz, Iran

4 Department of Anatomical Sciences, School of Medicine, Tehran University of Medical Science, Tehran, Iran

Abstract

Objective(s)
Sildenafil citrate is a new drug and has special properties that bring about nitric oxide effects on vascular smooth muscle. The aim of this study was to assess the effects of ovarian stimulation and sildenafil citrate injection on pinopode expression in mice.
Materials and Methods
Thirty adult female mice were randomly divided into three groups: control, hyperstimulated and hyperstimulated +sildenafil citrate injection. In experimental groups mice received 7.5 IU human menopausal gonadotropin (HMG) and then after 48 hr received 7.5 IU human chorionic gonadotropic (HCG) hormones. After that every two females were put with one male in one cage for mating. Hyperstimulated +sildenafil citrate group were injected with sildenafil citrate (3 mg/mouse) every 24 hr for three days, after HMG injection. The animals were sacrificed by cervical dislocation 96 hr after HMG injection, and their uterine specimens (the middle one-third) were prepared for transmission electron microscope studies.
Result
Electron microscopy observations showed that in the control group there were long and short microvilli while no developed pinopodes were observed, however, in the two other groups, well developed pinopodes were expressed 4 days after HMG injection.
Conclusion
The results showed that hyperstimulation of mice with sildenafil citrate may be more helpful in formation of pinopodes and implantation.

Keywords


1.Oborná I, Novotný R, Brezinová J, Petrová P, Lichnovský V, Fingerová H. Changes in the development of uterine pinopodes in steroid hormone supplemented cycles. Physiol Res 2004; 53:423-429.

2. Bentin-Ley U, Sjögren A, Nilsson L, Hamberger L, Larsen JF, Horn T. Presence of uterine pinopodes at the embryo-endometrial interface during human implantation in vitro. Hum Reprod 1999; 14:515-520.

3.Quinn C, Ryan E, Claessens EA, Greenblatt E, Hawrylyshyn P, Cruickshank B, et al. The presence of pinopodes in the human endometrium does not delineate the implantation window. Fertil Steril  2007; 87:1015-1021. Epub 2007 Jan 16.

4. Salehnia M. Different pattern of pinopodes expression in stimulated mouse endometrium. Exp Anim 2005; 54:349-352.

5. Salehnia M. Progesterone shifts the pinopodes expression of mouse endometrium to pre-implantation time after ovarian hyperstimulation. Iran J Reproductive Med? 2003; 1:20-23.

6. Kolb BA, Najmabadi S, Paulson RJ. Ultrastructural characteristics of the luteal phase endometrium in patients undergoing controlled ovarian hyperstimulation. Fertil Steril 1997; 67:625-630.

7. Stavreus-Evers A, Nikas G, Sahlin L, Eriksson H, Landgren BM. Formation of pinopodes in human endometrium is associated with the concentrations of progesterone and progesterone receptors.  Fertil Steril  2001; 76:782-791.

8. Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update  2006 ; 12:731-46. Epub 2006 Sep 18.

9. Paulus WE, Strehler E, Zhang M, Jelinkova L, El-Danasouri I, Sterzik K. Benefit of vaginal sildenafil in assisted reproduction therapy. Fertil Steril  2002; 77:846-847.

10. Sher G, Fisch JD. Vaginal sildenafil (Viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing IVF. Hum Reprod 2000; 15:806-809.

12. Boolell M, Gepi-Attee S, Gingell JC, Allen MJ. Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br J Urol  1996; 78:257-261.

12. Khan RN, Hamoud H, Warren A, Wong LF, Arulkumaran S. Relaxant action of sildenafil citrate (Viagra) on human myometrium of pregnancy: Am J Obstet Gynecol  2004; 191:315-321.

13. Lundkvist O, Nilsson BO. Ultrastructural changes of the trophoblast-epithelial complex in mice subjected to implantation blocking treatment with indomethacin. Biol Reprod 1980; 22:719-726.

14. Ertzeid G, Storeng R. The impact of ovarion stimulation on implantation and fetal development in mice. Hum Reprod  2001; 16:221-225.

15. Emadi M, Salehnia M. The morphological expression of endometrial pinopodes during implantation in mice after ovarian stimulation and progesterone injection. Yakhteh Med J 2004; 5: 140-145.

15. Nikas G, Develioglu OH, Toner JP, Jones HW Jr. Endometrial pinopodes indicate a shift in the window of receptivity in IVF cycles. Hum Reprod  1999; 14:787-792.

17. Nikas G, Drakakis P, Loutradis D, Mara-Skoufari C, Koumantakis E, Michalas S, et al. Uterine pinopodes as markers of the nidation window in cycling women receiving exogenous oestradiol and progesterone. Hum Reprod  1995; 10:1208-1213.

18. Singh MM, Chauhan SC, Trivedi RN, Maitra SC, Kamboj VP. Correlation of pinopode development on uterine luminal epithelial surface with hormonal events and endometrial sensitivity in rat. Eur Endocrinol 1996; 135:107-117.

19. Salehnia M, Arianmanesh M, Beigi M. The impact of ovarian stimulation on mouse endometrium: a morphometrical study.  Iran J Reproductive Med 2006; 4:7-11.

20. Ozgunen KT, Erdogan S, Mazmanoglu N, Pamuk I, Logoglu G, Ozgunen T. Effect of gonadotrophin dose on oocyte retrieval in superovulated BALB/c mice. Theriogenology 2001; 56:435-445.

21. Barroso RP, Osuamkpe C, Nagamani M, Yallampalli C. Nitric oxide inhibits development of embryo and implantation in mice. Mol Hum Reprod 1998; 4:503-507.