The prostate in women: an updated histological and immunohistochemical profile of the female periurethral glands and their relationship to an implanted midurethral sling.

BACKGROUND: There is evidence of glandular tissue in the region of the anterior vaginal wall-female periurethral tissue (AVW-FPT) that has similar morphology and immunohistochemistry to the prostate in men. Surgical injury to this tissue has been suggested as a potential cause of sexual dysfunction following midurethral sling (MUS) procedures. However, the anatomy and embryology of these glands have not been fully resolved. This has led to difficulties in classifying this tissue as a prostate and defining its clinical significance related to MUS procedures. AIM: To describe the histological and immunohistochemical characteristics of the female periurethral glands using markers of prostate tissue and innervation and to examine their anatomical relationships to an implanted MUS. METHODS: Using gross and fine dissection, the AVW-FPT was dissected from 9 cadavers. Prior to dissection, 2 cadavers underwent simulation of the MUS procedure by a urogynecologist. Samples were paraffin embedded and serially sectioned. Immunohistochemistry was performed using markers of prostate tissue and innervation. OUTCOMES: Immunohistochemical localization of markers for prostatic tissue and innervation of the glandular tissue of the AVW-FPT, including the region of MUS implantation. RESULTS: Female periurethral glands were immunoreactive for markers of male prostatic tissue, including prostate-specific antigen, androgen receptor, HOXB13, and NKX3.1. Markers of innervation (protein gene product 9.5, choline acetyl transferase, and vasoactive intestinal polypeptide) also localized to certain regions of the glandular tissue and associated blood supply. Surgical simulation of the MUS procedure demonstrated that some periurethral glands are located in close proximity to an implanted sling. CLINICAL TRANSLATION: The AVW-FPT contains glandular tissue in the surgical field of MUS implantation. Iatrogenic damage to the female periurethral glands and the associated innervation during surgery could explain the negative impacts on sexual dysfunction reported following MUS procedures. STRENGTHS AND LIMITATIONS: This is the first study to characterize the female periurethral glands using markers of prostatic tissue in concert with markers of general and autonomic innervation and characterize their anatomical relationships within the surgical field of MUS implantation. The small sample size is a limitation of this study. CONCLUSION: We provide further evidence that the AVW-FPT contains innervated glands that are phenotypically similar to the male prostate and may share a common embryonic origin. The microscopic and immunohistochemical features of the periurethral glands may be indicative of their functional capacity in sexual responses. The location of these glands in the surgical field of MUS procedures underscores the clinical significance of this tissue.

Immunohistochemical Investigation of Autonomic and Sensory Innervation of Anterior Vaginal Wall Female Periurethral Tissue: A Study of the Surgical Field of Mid-Urethral Sling Surgery Using Cadaveric Simulation.

BACKGROUND: Female sexual dysfunction, including female orgasm disorder, has been reported following mid-urethral sling (MUS) surgery to treat bothersome stress urinary incontinence. Anterior vaginal wall-female periurethral tissue (AVW-FPT) likely contains autonomic and sensory innervation involved in the female sexual response, and injury to these nerves may result from MUS implantation. AIM: To characterize, using fresh cadaveric tissue, autonomic and sensory nerves in AVW- FPT using immunohistochemistry (IHC), and to assess their proximity to an implanted MUS. METHODS: AVW-FPT was excised following careful dissection from four fresh cadavers. Prior to dissection, one cadaver underwent simulation of the MUS procedure by a urogynegologist, using a fascial sling. All samples were paraffin embedded, sectioned, and stained with hematoxylin. Serial sectioning and IHC were performed to identify nerves. IHC markers were used to characterize the sensory and autonomic innervation. OUTCOMES: IHC localization of autonomic and sensory nerve markers consistent with neural tissue within the region of MUS implantation. RESULTS: IHC of AVW-FPT using protein gene product 9.5 (PGP9.5), a general nerve stain, revealed innervation throughout the region targeted by the MUS implantation. More specifically, immunoreactivity for both autonomic (tyrosine hydroxylase, TH) and sensory (Nav1.8 and S100ß) nerves were found in close proximity (<1 mm) to the implanted MUS. In addition, a subset of S100ß positive nerves also showed immunoreactivity for calcitonin gene-related peptide (CGRP). Combining the IHC findings with the surgical simulation of the MUS implantation revealed the potential for damage to both autonomic and sensory nerves as a direct result of the MUS procedure. CLINICAL TRANSLATION: The identified autonomic and sensory nerves of the AVW-FPT may contribute to the female sexual response, and yet are potentially negatively impacted by MUS procedures. Given that surgeries performed on male genital tissue, including the prostate, may cause sexual dysfunction secondary to nerve damage, and that urologists routinely provide informed consent regarding this possibility, urogynaecologists are encouraged to obtain appropriate informed consent from prospective patients undergoing the MUS procedure. STRENGTHS & LIMITATIONS: This is the first study to characterize the sensory and autonomic innervation within the surgical field of MUS implantation and demonstrate its relationship to an implanted MUS. The small sample size is a limitation of this study. CONCLUSION: The present study provides evidence of potential injury to autonomic and sensory innervation of AVW-FPT as a consequence of MUS implantation, which may help explain the underlying mechanisms involved in the reported post-operative female sexual dysfunction in some women. Giovannetti O, Tomalty D, Gaudet D, et al. Immunohistochemical Investigation of Autonomic and Sensory Innervation of Anterior Vaginal Wall Female Periurethral Tissue: A Study of the Surgical Field of Mid-Urethral Sling Surgery Using Cadaveric Simulation. J Sex Med 2021;18:1168-1180.