Distribution of norepinephrine and acetylcholine receptors in ovarian structures across reproductive and senescent phases in rats

The autonomic nerves in the mammalian ovary are responsible for transmitting the neurotransmitters norepinephrine and acetylcholine, among others. Interestingly, some ovarian innervation becomes more active toward the end of life. The objective of this study was to examine the presence of adrenergic (A1R) and muscarinic (M1R) receptors in adult and senescent female rats. Female rats were divided into three groups according to age: young adults aged 3 to 5 months (3M), middle-aged rats aged 12 months (12M), and senescent rats aged 15 months (15M). Primary antibodies targeting the α1-adrenergic receptor, μ1-muscarinic receptor, 17β-estradiol receptor (ER), and α1-progesterone receptor (PR) were used. Immunoreactivity analysis covered the ovarian stroma and cells around functional structures such as the corpus luteum, ovarian cysts, and follicles. Both receptor antibodies stained these structures, but the noradrenergic binding was three times more abundant than cholinergic binding. The number of immunoreactive cells expressing the A1R/ER combination was significantly increased in 12M rats, principally around follicles or cysts. M1R/PR staining was similarly increased in the 12M group, but the principal signal source was the stroma cells. The autonomic nervous system appears to participate in the loss of function of these structures with age in the rat ovary. • In senescent rats, the link between A1R/M1R receptors and ovarian dysfunction is revealed. • A1R modulates estradiol secretion, driving follicular atresia in reproductive senescence. • Alterations in A1R and M1R receptors indicate a possible cause of ovarian dysfunction.