Role of the superior ovarian nerve in the regulation of follicular development and steroidogenesis in the morning of diestrus 1

Abstract

Purpose: Little is known about the role of the superior ovarian nerve (SON) in follicular development during the estrus cycle. The aim of the present study was to analyze the role of neural signals arriving through the SON at the ovaries in the regulation of follicular development and ovarian steroid secretion in diestrus 1 of cyclic rats.

Methods: Cyclic rats were subjected to left, right, or bilateral SON sectioning or to unilateral or bilateral laparotomy at diestrus 1 at 11:00 h. Animals were sacrificed 24 h after surgery.

Results: Compared to laparotomized animals, unilateral SON sectioning decreased the number of preovulatory follicles, while bilateral SON sectioning resulted in a decreased number of atretic preantral follicles. An important observation was the presence of invaginations in the follicular wall of large antral and preovulatory follicles in animals with denervation. Furthermore, left SON sectioning increased progesterone levels but decreased testosterone levels, which are effects that were not observed in animals that were subjected to right denervation.

Conclusions: At 11:00 h of diestrus 1, the SON was found to stimulate follicle development, possibly via neural signals, such as noradrenaline and/or vasoactive intestinal peptide, and this stimulation induced the formation of follicle-stimulating hormone receptors. The role of the SON in the regulation of ovarian steroid secretion is asymmetric: the left SON inhibits the regulation of progesterone and stimulates testosterone secretion, and the right nerve does not participate in these processes.

Keywords: Follicular development; Gonadotropins; Noradrenaline; Ovarian steroidogenesis; Superior ovarian nerve.

Fig. 1

Schematic representation of a laparotomy and b superior ovarian nerve sectioning

Fig. 2

Effects of unilateral (left or right) or bilateral laparotomy (LAP) on follicular development. Mean ± S.E.M. total number of (healthy+atretic) (a) or atretic (b) follicles in untreated control rats or rats subjected to left (LAP-L), right (LAP-R), or bilateral (LAP-B) laparotomy performed at 11:00 h of diestrus 1. *p < 0.05 vs. control (Kruskal-Wallis followed by Dunn’s test)

Fig. 3

Micrographs correspond to the largest section of one ovary of animals control (a) or with right laparotomy (b); images were captured with a × 5 microscopic lens. High magnification of each class of follicles in the ovaries: preantral follicle, PAF (c); small antral follicle, SAF (d); large antral follicle, LAF (e); and preovulatory follicle, PF (f). Images were captured with a × 10 microscopic lens

Fig. 4

Effects of unilateral (left or right) or bilateral superior ovarian nerve (SON) sectioning on steroid and protein hormone levels. Mean ± S.E.M. serum progesterone (a), testosterone (b), estradiol (c), follicle-stimulating hormone (FSH) (d), and luteinizing hormone (LH) (e) levels in rats with left, right, or bilateral laparotomy (LAP) or SON sectioning performed at 11:00 h of diestrus 1. *p < 0.05 vs. their corresponding LAP group (Student’s t test)

Fig. 5

Effects of unilateral (left or right) or bilateral superior ovarian nerve (SON) sectioning on ovarian noradrenaline levels. Mean ± S.E.M. ovarian noradrenaline levels in rats with left, right, or bilateral laparotomy (LAP) or with left, right, or bilateral SON sectioning performed at 11:00 h of diestrus 1. *p < 0.05 vs. their corresponding LAP group (ANOVA followed by Tukey’s test)

Fig. 6

Effects of unilateral (left or right) or bilateral superior ovarian nerve (SON) sectioning on follicular development. Mean ± S.E.M. total number of healthy+atretic (a) or atretic (b) follicles in rats with left (LAP-L), right (LAP-R), or bilateral (LAP-B) laparotomy or with left (SON-L), right (SON-R), or bilateral (SON-B) SON sectioning performed at 11:00 h of diestrus 1. *p < 0.05 vs. their corresponding LAP group; ♦p < 0.05 vs. SON-L (Kruskal-Wallis followed by Dunn’s test)

Fig. 7

Micrographs showing atretic follicles from animals with sectioning of the SON. Pyknosis of the granulosa cells and desquamation into the follicular antrum (black arrows) in large antral follicles (a, b); images were captured with a × 40 microscopic lens. Fragmented oocytes (blue arrows) in small antral follicles (c–e); images were captured with a × 40 microscopic lens

Fig. 8

Ovarian histology of rats with unilateral or bilateral superior ovarian nerve (SON) sectioning. Micrographs of ovaries from a rat with sectioning of the SON performed during diestrus 1 at 11.00 h showing a large antral follicle (351–500 μm) with invaginations in the granulosa cell layer (arrows) (a) and a preovulatory follicle (> 500 μm) with loss of structure (disorganization) of the granulosa cell layer (arrows) (b). Large antral and preovulatory follicles of the ovaries from control rats (c, d). Images were captured with a × 10 microscopic lens