Loma Linda University

Enrollment Information
Call us at: 909-558-1000

Faculty Directory
Michael Kirby, PhD
Professor, Pathology and Human Anatomy
School of Medicine
Professor, Basic Sciences
School of Medicine
Member, Faculty of Graduate Studies
Publications    Scholarly Journals--Submitted
  • M. A. Kirby, M. M. Groves, and S. M. Yellon, Retrograde tracing of spinal cord connections to the cervix with pregnancy in mice. J. of Reproduction, 139:1-10,2009. ( 1/2009 - 8/2009 )
  Scholarly Journals--Published
  • Boyd J.W., T.J. Lechuga, C.A. Ebner, M.A. Kirby, Yellon S.M., Cervix remodeling and parturition in the rat: lack of a role for hypogastric innervation. J. of Reproduction 137: 739-748, 2009.   ( 1/2009 - 8/2009 )
  • Yellon S.M., Burns A.E., J.L. See, T.J. Lechuga, M.A. Kirby, Progesterone Withdrawal Promotes Remodeling Processes in the Nonpregnant Mouse Cervix. Biol. Reprod. 81: 1-6, 2009.  ( 1/2009 - 6/2009 )
  • Kirby, LS, and MA Kirby. "Functional Neuroanatomy An Interactive Text and Manual." J. of Neurosurgery 2006,102.: 959-960. ( 8/2006 )
    Book Review
  • Kirby, LS, Kirby, MA, Warren, JW, Tran, TT, and SJ Yellon.. "Increased innervation and ripening of the prepartum murine cervix." J. Gynecol.. Investigations . 12:578-85, 2005 ( 8/2005 )
  • Kirby, LS, and MA Kirby. "Functional Neuroanatomy An Interactive Text and Manual." J. of Neurosurgery 102. (2005): 959-960. ( 1/2005 )
  • Yellon S M, Dobyns A E, Beck H L, Kurtzman J T, Garfield R E, & Kirby M A. (2013). Loss of Progesterone Receptor-Mediated Actions Induce Preterm Cellular and Structural Remodeling of the Cervix and Premature Birth. PLoS One, 8(12), 9. ( 12/2013 - Present ) Link...
    A decline in serum progesterone or antagonism of progesterone receptor function results in preterm labor and birth. Whether characteristics of premature remodeling of the cervix after antiprogestins or ovariectomy are similar to that at term was the focus of the present study. Groups of pregnant rats were treated with vehicle, a progesterone receptor antagonist (onapristone or mifepristone), or ovariectomized on day 17 postbreeding. As expected, controls given vehicle delivered at term while rats delivered preterm after progesterone receptor antagonist treatment or ovariectomy. Similar to the cervix before term, the preterm cervix of progesterone receptor antagonist-treated rats was characterized by reduced cell nuclei density, decreased collagen content and structure, as well as a greater presence of macrophages per unit area. Thus, loss of nuclear progesterone receptor-mediated actions promoted structural remodeling of the cervix, increased census of resident macrophages, and preterm birth much like that found in the cervix at term. In contrast to the progesterone receptor antagonist-induced advance in characteristics associated with remodeling, ovariectomy-induced loss of systemic progesterone did not affect hypertrophy, extracellular collagen, or macrophage numbers in the cervix. Thus, the structure and macrophage census in the cervix appear sufficient for premature ripening and birth to occur well before term. With progesterone receptors predominantly localized on cells other than macrophages, the findings suggest that interactions between cells may facilitate the loss of progesterone receptor-mediated actions as part of a final common mechanism that remodels the cervix in certain etiologies of preterm and with parturition at term.
  • Clyde L A, Lechuga T J, Ebner C A, Burns A E, Kirby M A, & Yellon S M. (2011). Transection of the Pelvic or Vagus Nerve Forestalls Ripening of the Cervix and Delays Birth in Rats. Biology of Reproduction, 84(3), 587-594. ( 3/2011 - Present ) Link...
    Innervation of the cervix is important for normal timing of birth because transection of the pelvic nerve forestalls birth and causes dystocia. To discover whether transection of the parasympathetic innervation of the cervix affects cervical ripening in the process of parturition was the objective of the present study. Rats on Day 16 of pregnancy had the pelvic nerve (PnX) or the vagus nerve (VnX) or both pathways (PnX+VnX) transected, sham-operated (Sham) or nonpregnant rats served as controls. Sections of fixed peripartum cervix were stained for collagen or processed by immunohistochemistry to identify macrophages and nerve fibers. All Sham controls delivered by the morning of Day 22 postbreeding, while births were delayed in more than 75% of neurectomized rats by more than 12 h. Dystocia was evident in more than 25% of the PnX and PnX+VnX rats. Moreover, on prepartum Day 21, serum progesterone was increased severalfold in neurectomized versus Sham rats. Assessments of cell nuclei counts indicated that the cervix of neurectomized rats and Sham controls had become equally hypertrophied compared to the unripe cervix in nonpregnant rats. Collagen content and structure were reduced in the cervix of all pregnant rats, whether neurectomized or Shams, versus that in nonpregnant rats. Stereological analysis of cervix sections found reduced numbers of resident macrophages in prepartum PnX and PnX+VnX rats on Day 21 postbreeding, as well as in VnX rats on Day 22 postbreeding compared to that in Sham controls. Finally, nerve transections blocked the prepartum increase in innervation that occurred in Sham rats on Day 21 postbreeding. These findings indicate that parasympathetic innervation of the cervix mediates local inflammatory processes, withdrawal of progesterone in circulation, and the normal timing of birth. Therefore, pelvic and vagal nerves regulate macrophage immigration and nerve fiber density but may not be involved in final remodeling of the extracellular matrix in the prepartum cervix. These findings support the contention that immigration of immune cells and enhanced innervation are involved in processes that remodel the cervix and time parturition.
  • Yellon S M, Grisham L A, Rambau G M, Lechuga T J, & Kirby M A. (2010). Pregnancy-related changes in connections from the cervix to forebrain and hypothalamus in mice. Reproduction, 140(1), 155-164. ( 7/2010 - Present ) Link...
    The transneuronal tracer pseudorabies virus was used to test the hypothesis that connections from the cervix to the forebrain and hypothalamus are maintained with pregnancy. The virus was injected into the cervix of nonpregnant or pregnant mice, and, after 5 days, virus-labeled cells and fibers were found in specific forebrain regions and, most prominently, in portions of the hypothalamic paraventricular nucleus. With pregnancy, fewer neurons and fibers were evident in most brain regions compared to that in nonpregnant mice. In particular, little or no virus was found in the medial and ventral parvocellular subdivisions, anteroventral periventricular nucleus, or motor cortex in pregnant mice. By contrast, labeling of virus was sustained in the dorsal hypothalamus and suprachiasmatic nucleus in all groups. Based upon image analysis of digitized photomicrographs, the area with label in the rostral and medial parvocellular paraventricular nucleus and magnocellular subdivisions was significantly reduced in mice whose cervix was injected with virus during pregnancy than in nonpregnant mice. The findings indicate that connections from the cervix to brain regions that are involved in sensory input and integrative autonomic functions are reduced during pregnancy. The findings raise the possibility that remaining pathways from the cervix to the forebrain and hypothalamus may be important for control of pituitary neuroendocrine secretion, as well as for effector functions in the cervix as pregnancy nears term. Reproduction (2010) 140 155-164
  • Kirby M A, Groves M M, & Yellon S M. (2010). Retrograde tracing of spinal cord connections to the cervix with pregnancy in mice. Reproduction, 139(3), 645-653. ( 3/2010 - Present ) Link...
    In contrast to the uterus, the cervix is well innervated during pregnancy and the density of nerve fibers increases before birth. To assess neural connections between the cervix and the spinal cord, the cervix of pregnant mice was injected with the trans-synaptic retrograde neural tract tracer pseudorabies virus (PRV). After 5 days, the virus was present in nerve cells and fibers in specific areas of the sensory, autonomic, and motor subdivisions of the thoracolumbar spinal cord. In nonpregnant controls, the virus was predominantly distributed in laminae I-III in the dorsal gray sensory areas with the heaviest label in the substantia gelatinosa compared with the autonomic or motor areas. Labeled cells and processes were sparse in other regions, except for a prominent cluster in the intermediolateral column (lamina VII). Photomicrographs of spinal cord sections were digitized, and the total area with the virus was estimated. Compared with nonpregnant controls, the area with PRV was significantly decreased in all the spinal cord subdivisions in pregnant mice except in the intermediolateral column. However, areas with the virus were equivalent in mice injected with PRV at 4 days or 1 day before birth. These findings suggest that the predominant innervation of the murine cervix is from the sensory regions of the thoracolumbar spinal cord, and that these connections diminish with pregnancy. The results raise the possibility that the remaining connections from sensory and autonomic subdivisions, particularly the intermediolateral column, of the thoracolumbar spinal cord may be important for increased density of nerve fibers in the cervix as pregnancy nears term. Reproduction (2010) 139 645-653
  • Anissian L, Kirby M, & Stark A. (2009). Primary cortical brain cells influence osteoblast activity. Biochemical and Biophysical Research Communications, 390(3), 410-414. ( 12/2009 - Present ) Link...
    The presence of neuropeptides and neuroreceptors in the bone have been reported in several studies. Bone turn-over seems to be controlled by the nervous system. The actual pathway or the control mechanism is still under investigation. In this study we investigate the changes in osteoblast cells if they are in co-culture with primary cortical brain cells. After seven days in co-culture with the primary fetal brain cells the osteoblast cells exhibited hypertrophic morphological changes and showed stronger ALP activity. (C) 2009 Elsevier Inc. All rights reserved.
  • Yellon S M, Burns A E, See J L, Lechuga T J, & Kirby M A. (2009). Progesterone Withdrawal Promotes Remodeling Processes in the Nonpregnant Mouse Cervix. Biology of Reproduction, 81(1), 1-6. ( 7/2009 - Present ) Link...
    Prepartum cervical ripening is associated with remodeling of collagen structure and with inflammation. Progesterone withdrawal is critical for parturition, but the effects of progesterone decline on cervical morphology are unknown. The present study tested the hypothesis that progesterone withdrawal promotes processes associated with remodeling of the cervix. Adult, virgin, female C57BL/6 mice received silastic capsules with oil vehicle or estradiol plus progesterone to parallel concentrations in circulation during pregnancy. After 17 days of estradiol and progesterone treatment, the progesterone implant was removed from one group. Mice in each group were killed 15, 18, or 19 days after placement of capsules. Sections of cervix were stained for collagen, and the densities of macrophages, neutrophils, and area with nerve fibers were assessed. Treatment with gonadal steroids promoted hypertrophy of the cervix, as well as reduced collagen and increased area with nerve fibers compared with vehicle-treated controls. Removal of the progesterone capsule did not affect hypertrophy or innervation, but it did reduce collagen. By contrast, significantly more macrophages and neutrophils were present in the cervix on Days 18 and 19 (i.e., by 24 and 48 h after withdrawal of the progesterone capsule); the immune cell census was equivalent to that in vehicle controls. Findings indicate that gonadal steroids, comparable to those during pregnancy, promote hypertrophy and suppress immigration of immune cells in the cervix. Therefore, in a nonpregnant murine model for parturition, progesterone withdrawal is suggested to recruit immune cells and processes that remodel the cervix.
  • Boyd J W, Lechuga T J, Ebner C A, Kirby M A, & Yellon S M. (2009). Cervix remodeling and parturition in the rat: lack of a role for hypogastric innervation. Reproduction, 137(4), 739-748. ( 4/2009 - Present ) Link...
    The hypogastric nerve is a major pathway innervating the uterine cervix, yet its contribution to the processes of cervical ripening and parturition is not known. The main objective of this study was to determine the effect of hypogastric nerve transection on remodeling of the cervix and timing of birth. As an initial goal, processes associated with remodeling of the peripartum cervix were studied. The cervix was obtained from time-dated pregnant rats on days 15, 19, 21, and 21.5 of pregnancy, and postpartum on the day of birth (day 22). The cervix was excised, post-fixed overnight, and sections stained to evaluate collagen content and structure or processed by immunohistochemistry to identify macrophages or nerve fibers. The census of macrophages and density of nerve fibers in the cervix peaked on day 21, the day before birth, and then declined postpartum. These results replicate in time course and magnitude previous studies in mice. To address the main objective, the hypogastric nerve was bilaterally transected on day 15 post-breeding; sham-operated rats served as controls. Pups were born in both groups at normal term. Transection of the hypogastric nerves did not affect remodeling of collagen or the census of macrophages or the density of nerve fibers in the cervix. These findings support the contention that enhanced innervation and immigration of immune cells are associated with remodeling of the cervix and parturition, but that a neural pathway other than the hypogastric nerve may participate in the process of cervical ripening.
  • Yellon S M, Lechuga T J, Burns A E, & Kirby M A. (2009). Transection of the Vagus Nerve Delays Birth and Alters Cervical Ripening in Rat. Reproductive Sciences, 16(3), 302A-302A. ( 3/2009 - Present )
  • Grisham L A, Rambau G, Kirby M A, & Yellon S M. (2009). PREGNANCY-RELATED REDUCTION IN CONNECTIONS FROM THE CERVIX TO THE HYPOTHALAMIC PARAVENTRICULAR NUCLEUS. Journal of Investigative Medicine, 57(1), 133-133. ( 1/2009 - Present )