Rat Ovarian Function Is Impaired during Experimental Autoimmune Encephalomyelitis.

Area of Science:

• Neuroimmunology
• Reproductive Endocrinology
• Endocrinology

Background:

• Multiple sclerosis (MS) is a prevalent autoimmune disease of the central nervous system (CNS), disproportionately affecting women.
• Sex hormones significantly modulate immune responses in both MS and its animal models.
• Previous work demonstrated experimental autoimmune encephalomyelitis (EAE) impacts the hypothalamic-pituitary-gonadal axis and disrupts the estrous cycle in female rats.

Purpose of the Study:

• To investigate the gonadal status in female rats experiencing EAE.
• To analyze ovarian morphometrics, sex steroid levels (circulating and intraovarian), and steroidogenic gene/protein expression in ovarian tissue.

Main Methods:

• Assessment of ovarian morphometric parameters.
• Measurement of circulating and intraovarian sex steroid levels.
• Analysis of steroidogenic machinery component expression (gene and protein) in ovarian tissue.

Main Results:

• EAE induced a prolonged diestrus state, resembling pseudopregnancy, with maintained corpora lutea and elevated intraovarian progesterone.
• Increased StAR gene and protein expression was observed.
• Decreased CYP17A1 protein led to reduced ovarian testosterone and estradiol, despite slightly increased serum testosterone and unchanged serum estradiol, indicating extra-gonadal regulation.

Conclusions:

• Central autoimmunity, as modeled by EAE, significantly alters female reproductive system function.
• Bidirectional interactions exist between hormonal status and EAE progression.
• Extra-gonadal factors play a crucial role in regulating circulating sex steroid levels during EAE.