Betaine Attenuates The Expression of Vasoactive Mediators and Histological Alterations Associated with Ovarian Hyperstimulation Syndrome in Rats

Ovarian hyperstimulation syndrome (OHSS) is one female reproductive disorder that can occur afteradministration of injectable hormonal drugs to stimulate ovulation. Betaine (BET) is an intracellular biomolecule withanti-inflammatory and tissue protective effects. There is no information about its effects in an experimental model ofOHSS. The current study aims to investigate the possible effects of BET on abnormal expressions of vasoconstrictorproteins and ovarian histological changes in an experimental OHSS rat model. In this experimental study, 30 adult female rats (two months old) were randomly divided intosix groups (n=5 per group): i. Control, ii. OHSS [10 IU sc equine chorionic gonadotropin (eCG) for 4 days followed by30 IU sc human chorionic gonadotropin (hCG) on the fifth day], iii. OHSS+BET (200 mg/kg/day, orally for seven days),iv. OHSS+Cabergoline (CAB, 100 mg/kg/day, orally for six days), v. BET, and vi. CAB. Expression levels of vascularendothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), and blood levels of oestradiol (E2) and progesterone(P4) were measured at the end of the experiment. The ovaries were studied for histomorphological changes. Induction of OHSS altered tissue histology, including an increase in the number of corpora lutea and atreticfollicles, and decreased the number of follicular reserves. In this group, we observed increased expressions of theVEGF and COX-2 proteins, and increased serum E2 and P4 levels. Administration of CAB and BET significantlyattenuated all molecular and histological alterations observed in the OHSS animals. Our findings, for first time, indicate the beneficial effects of BET to reduce OHSS complications in patientsby reducing the expressions of vasoactive proteins and improving changes to the ovarian tissues. The findings aresimilar to CAB and can be a new avenue for future research on BET.