The prostate is a sexual accessory gland that contributes to the seminal fluid. Its function is under endocrine and neural control. Rodent prostate consists of three histological distinctive paired lobes: ventral, lateral and dorsal. Prostate innervation is provided by the paired major pelvic ganglion (MPG) [1], which contains afferent inputs from the hypogastric and pelvic nerves, as well as efferent commissural nerves [2]. Unilateral ablation of MPG (MPGA) produces ventral prostate atrophy, however, the effect of the denervation on the other lobes has not been analyzed. We hypothesize that MPGA differentially affects the prostate lobes. In addition, considering the high interrelationship between the two MPGs, recovery is expected at long term due contralateral reinnervation. The aim of this study was to determine in rats the effect of the unilateral MPGA on the morphometric characteristics of the prostatic ventral, lateral and dorsal lobes; at short (3 weeks after MPG ablation) and long term (20 weeks after ablation).

The experimental protocol was approved by the University Committee on Laboratory Animals, according to the guidelines of the Mexican Council on Laboratory Animals Care (NOM-062-ZOO-1999) and NIH Guide for the Care and Use of Laboratory Animals. We employed 9 adult Wistar male rats (300–350 g) assigned to three groups: Sham surgery (SH, n=3), two weeks after MPGA (MPGA-2; n=3) and 20 weeks after MPGA procedure (MPGA-20, n=3). MPGA were conducted in animals anesthetized with ketamine (100 mg / kg) and xylazine (IP, 10 mg / kg), by intraperitoneal injection. A laparotomy was performed and the left lateral lobe of the prostate was located. Attached to this lobe the left MPG was found. It was dissected and removed. The abdominal muscles and the skin was sutured in two layers. The animals were kept on a warm plate until they recovered from anesthesia. Later, they were moved to the animal facility where their health conditions and skin healing was reviewed daily. Antibiotic (Baytril, 2.5 mg / kg) and analgesic (diclofenac 1 mg / kg) were administered for three days after surgery. After 3 or 20 weeks of surgery, the animals were re-anesthetized and the prostate lobes collected and immersed in 10% formalin. Then the tissue was embedded in paraffin, sectioned (5 μm thickness) and stained with a Masson´s tricrome technique. The sections were observed with a light microscope. Photographs were taken with a digital camera. The morphological characteristics of the prostate lobes and alveolar density were analyzed. The height of the epithelial cells of the right and left lobes of the prostate were measured using Axiovision image processing software (version 4.5, Carl Zeiss). Statistical analysis was performed using Sigma Plot Software (version 12, Systat Software, Inc.). Paired Student´s t-test (between left and right sides) and ANOVA (between groups) were used to analyze the data. P values of <0.05 indicated a statistically significant difference for statistical comparisons.

In SH animals, the ventral lobes were the largest lobes, most of their area were in close anatomical relation to the urinary bladder. The dorsal lobes were dorsal to the seminal ducts, its lower region covered the dorsal wall of the rostral urethra. The lateral lobes were in direct relation to the rostral portion of the urethra, their ducts intermingled with fibers of the external urethral sphincter. There were no significant morphological differences between the left and right prostate lobes of SH animals, neither in the area of the alveoli or in the height of the epithelium. Similarly, there was not significant changes in size or morphology of the left and right prostate lobes after MPG-ablation. However, MPGA-3 and MPGA-20 significantly decreased the alveolar density (p<0.05) and the height of the prostate epithelium, in the three lobes. Considering the values obtained in right lobes (innervated side) as 100%, the height of the ventral prostate lobe epithelium ipsilateral to the MPGA decreased to 38% in MPGA-2 animals and to 23% in MPGA-20. The height of the lateral prostate lobe epithelium ipsilateral to the MPGA decreased to 63% in MPGA-2 animals and to 62% in MPGA-20. The height of the dorsal prostate lobe epithelium ipsilateral to the MPGA decreased to 82% in MPGA-2 animals and to 70% in MPGA-20. The area of the alveoli significantly increased in the ventral lobe ipsilateral to the ablation in both groups, MPGA-2 (p<0.05) and MPG-20 (p<0.01). The alveolar area of the lateral and dorsal lobe has a tendency to increase but there was not statistical significant differences.

The findings indicate that MPGA affects the ventral prostate lobe more than the lateral and dorsal, ipsilateral to the ablation, which indicates that the ventral lobe is fully innervated by MPG. The fact that the lateral and dorsal lobes are partially affected suggest that these lobes may have other source of innervation, such as the accessory ganglia or contralateral innervation via MPG commisural nerves. No significant recovery was observed at long term, which indicates that MPG-A leads to prostate functional permanently dysfunction

It is concluded that MPG-A differentially affects the lobes of the prostate, with more effect on the ventral lobes. However, these lobes are more anatomically related to the bladder than the urethra. This information should be considered in preclinical studies of autonomic nerve influencing prostate cancer in rat model [3], where ventral lobe outcome measures have been analyzed.

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