Cyclic Changes of Nerve Fibers in Human Endometrium

Abstract

Objective: The presence of nerve fibers in human endometrium remains unsettled but recent immunocytochemical studies have shown that there was increased innervation in the endometrium from women with endometriosis and some nerve fibers in the normally cycling human endometrium. In the current study, we used uterine tissue cryosections from normal cycling women, which previously provided better immunocytochemical staining for lymphatic vessels than in paraffin sections. Materials and Methods: A total of 16 cases from normally cycling women were included representing menstrual, early proliferative, early to late secretary phase. Neurofilament and CD 56 were used as immunocytochemical markers for nerve fibers with cryosections. Results: There were consistent presence of nerve fibers in myometrium and basalis. Few small nerve fibers were identified in early proliferative endometrium and more nerve fibers were present in lower-half functionalis from mid-secretary phase. Late-secretary functionalis showed less nerve fibers in the upper-half than the lower-half functionalis, implying growing nerve fibers from lower functionalis to upper functionalis in late-secretary phase. Conclusion: Nerve fibers appeared to cyclically grow from basalis to lower functionalis and then from lower functionalis to upper functionalis concomitantly with blood vessels in normally cycling human endometrium. These cycling endometrial nerve fibers consisted mostly of nonmyelinated small nerve fibers, which may transmit pelvic pain in the normally cycling women.

Immunohistochemical staining for nerve fibers in normal tissues with frozen sections: Structure and Function Relationship

“…Additional monkeys were inserted with Silastic IUD (6 cm) into uterine cavity filled with an IUD containing progesterone antagonist, ZK 23011 (Leiras OY, Finland), which was kept for 5 months 28 . After the normal organs and uterus had been removed, a wedge of tissue from the inner endometrial surface to the myometrium including the full thickness of endometrium and contiguous myometrium was taken as described before at an average tissue size of 1 x 1 x 0.4 cm [12][13][14] . Fresh wedge tissues were microwave-irradiated for 7 sec in a microwave oven, embedded in OCT, frozen in liquid propane in the liquid nitrogen bath and frozen sectioned at 5 -7 µm [12][13][14] .…”

“…After the normal organs and uterus had been removed, a wedge of tissue from the inner endometrial surface to the myometrium including the full thickness of endometrium and contiguous myometrium was taken as described before at an average tissue size of 1 x 1 x 0.4 cm [12][13][14] . Fresh wedge tissues were microwave-irradiated for 7 sec in a microwave oven, embedded in OCT, frozen in liquid propane in the liquid nitrogen bath and frozen sectioned at 5 -7 µm [12][13][14] . Frozen sections were mounted on Super Frost Plus slide (Fisher Scientific, Pittsburgh, PA), microwave-irradiated again on ice for 3 sec, fixed in 2% paraformaldehyde in phosphate buffer at pH 7.4 for 10 to15 min at room temperature, and immersed twice for 2 min each in 85% ethanol [12][13][14] .…”

“…Fresh wedge tissues were microwave-irradiated for 7 sec in a microwave oven, embedded in OCT, frozen in liquid propane in the liquid nitrogen bath and frozen sectioned at 5 -7 µm [12][13][14] . Frozen sections were mounted on Super Frost Plus slide (Fisher Scientific, Pittsburgh, PA), microwave-irradiated again on ice for 3 sec, fixed in 2% paraformaldehyde in phosphate buffer at pH 7.4 for 10 to15 min at room temperature, and immersed twice for 2 min each in 85% ethanol [12][13][14] . Sections were incubated with blocking serum for 20 min and then with monoclonal anti-human NF (clone 2F11) and monoclonal CD56 (Dako System, Carpenteria, CA) at 1:100 dilutions overnight at 4°C, respectively.…”

“…Skin biopsy for the assessment of intradermal sensory nerve fiber using the pan-axonal marker, PGP 9.5 is an established clinical and research technique, and this technique may also be used to assess other population of nerve fibers in the other tissues [8][9][10][11] . We had previously utilized immunohistochemical staining with frozen sections for immunostaining lymphatic and blood vessels with normal monkey tissues 12,13 and extended this staining technique to immunostain peripheral nerve fibers in the normal tissues 14 . The current study aimed to detect the presence of nerve fibers in normal tissues including heart, lung, small intestine, large intestine, diaphragm, spleen, pancreas, adrenal gland, kidney, urinary bladder, vagina and normally cycling endometrium.…”

Neural plasticity of the uterus: New targets for endometrial cancer?

“… 26 Nevertheless, the identification of nerve fibers in the functional layer of non-pathological endometrium is controversial, and it could be relationated with hormonal changes of reproductive cycle. 27 …”