Allopregnanolone alters follicular and luteal dynamics during the estrous cycle

JOANA ANTONELA ASENSIO; ANTONELLA ROSARIO RAMONA CÁCERES; LAURA TATIANA PELEGRINA; MARÍA DE LOS ÁNGELES SANHUEZA; LEOPOLDINA SCOTTI; FERNANDA PARBORELL; MYRIAM RAQUEL LACONI

REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2018

1477-7827

Background: Allopregnanolone is a neurosteroid synthesized in the central nervous system independently ofsteroidogenic glands; it influences sexual behavior and anxiety. The aim of this work is to evaluate the indirect effect ofa single pharmacological dose of allopregnanolone on important processes related to normal ovarian function, such asfolliculogenesis, angiogenesis and luteolysis, and to study the corresponding changes in endocrine profile andenzymatic activity over 4 days of the rat estrous cycle. We test the hypothesis that allopregnanolone may triggerhypothalamus - hypophysis - ovarian axis dysregulation and cause ovarian failure which affects the next estrous cyclestages.Methods: Allopregnanolone was injected during the proestrous morning and then, the animals were sacrificed ateach stage of the estrous cycle. Ovarian sections were processed to determine the number and diameter of differentovarian structures. Cleaved caspase 3, proliferating cell nuclear antigen, α-actin and Von Willebrand factor expressionswere evaluated by immunohistochemistry. Luteinizing hormone, prolactin, estrogen and progesterone serumlevels were measured by radioimmunoassay. The enzymatic activities of 3β-hydroxysteroid dehydrogenase,3α-hydroxysteroid oxidoreductase and 20α-hydroxysteroid dehydrogenase were determined by spectrophotometricassays. Two-way ANOVA followed by Bonferroni was performed to determine statistical differences between controland treated groups along the four stages of the cycle.Results: The results indicate that allopregnanolone allopregnanolone decreased the number of developing follicles,while atretic follicles and cysts increased with no effects on normal cyclicity. Some cysts in treated ovaries showedmorphological characteristics similar to luteinized unruptured follicles. The apoptosis/proliferation balance increased infollicles from treated rats. The endocrine profile was altered at different stages of the estrous cycle of treated rats. Theangiogenic markers expression increased in treated ovaries. As regards corpora lutea, the apoptosis/proliferationbalance and 20α-hydroxysteroid dehydrogenase enzymatic activity decreased significantly. Progesterone levels and3β-hydroxysteroid dehydrogenase enzymatic activity increased in treated rats. These data suggest thatallopregnanolone interferes with steroidogenesis and folliculogenesis at different stages of the cycle.Conclusion: Allopregnanolone interferes with corpora lutea regression, which might indicate that this neurosteroidexerts a protective role over the luteal cells and prevents them from luteolysis. Allopregnanolone plays an importantrole in the ovarian pathophysiology.Keywords: Allopregnanolone, Folliculogenesis, Angiogenesis, Apoptosis, Steroidogenesis, Corpora lutea, Luteolysis* Correspondence: