scholarly journals Beyond the brain-Peripheral kisspeptin signaling is essential for promoting endometrial gland development and function

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Silvia León ◽  
Daniela Fernandois ◽  
Alexandra Sull ◽  
Judith Sull ◽  
Michele Calder ◽  
...  
Keyword(s):  
Genetically Modified ◽  
Central Control ◽  
Endometrial Gland ◽  
Physiological Relevance ◽  
Gnrh Neurons ◽  
Uterine Growth ◽  
Genetically Modified Mice ◽  
And Function ◽  
Gland Development ◽  
The Brain

Abstract Uterine growth and endometrial gland formation (adenogenesis) and function, are essential for fertility and are controlled by estrogens and other regulators, whose nature and physiological relevance are yet to be elucidated. Kisspeptin, which signals via Kiss1r, is essential for fertility, primarily through its central control of the hypothalamic-pituitary-ovarian axis, but also likely through peripheral actions. Using genetically modified mice, we addressed the contributions of central and peripheral kisspeptin signaling in regulating uterine growth and adenogenesis. Global ablation of Kiss1 or Kiss1r dramatically suppressed uterine growth and almost fully prevented adenogenesis. However, while uterine growth was fully rescued by E2 treatment of Kiss1 −/− mice and by genetic restoration of kisspeptin signaling in GnRH neurons in Kiss1r −/− mice, functional adenogenesis was only marginally restored. Thus, while uterine growth is largely dependent on ovarian E2-output via central kisspeptin signaling, peripheral kisspeptin signaling is indispensable for endometrial adenogenesis and function, essential aspects of reproductive competence.

scholarly journals Erratum: Corrigendum: Beyond the brain-Peripheral kisspeptin signaling is essential for promoting endometrial gland development and function

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Silvia León ◽  
Daniela Fernandois ◽  
Alexandra Sull ◽  
Judith Sull ◽  
Michele Calder ◽  
...  
Keyword(s):  
Endometrial Gland ◽  
And Function ◽  
Gland Development ◽  
The Brain

scholarly journals The severity of mammary gland developmental defects is linked to the overall functional status of Cx43 as revealed by genetically modified mice

2012 ◽  
Vol 449 (2) ◽  
pp. 401-413 ◽  
Author(s):  
Michael K. G. Stewart ◽  
Xiang-Qun Gong ◽  
Kevin J. Barr ◽  
Donglin Bai ◽  
Glenn I. Fishman ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Gap Junction ◽  
Connexin 43 ◽  
Mammary Gland Development ◽  
Genetically Modified ◽  
Milk Ejection ◽  
Gap Junction Channel ◽  
Genetically Modified Mice ◽  
And Function ◽  
Gland Development

Genetically modified mice mimicking ODDD (oculodentodigital dysplasia), a disease characterized by reduced Cx43 (connexin 43)-mediated gap junctional intercellular communication, represent an in vivo model to assess the role of Cx43 in mammary gland development and function. We previously reported that severely compromised Cx43 function delayed mammary gland development and impaired milk ejection in mice that harboured a G60S Cx43 mutant, yet there are no reports of lactation defects in ODDD patients. To address this further, we obtained a second mouse model of ODDD expressing an I130T Cx43 mutant to assess whether a mutant with partial gap junction channel activity would be sufficient to retain mammary gland development and function. The results of the present study show that virgin Cx43I130T/+ mice exhibited a temporary delay in ductal elongation at 4 weeks. In addition, Cx43I130T/+ mice develop smaller mammary glands at parturition due to reduced cell proliferation despite similar overall gland architecture. Distinct from Cx43G60S/+ mice, Cx43I130T/+ mice adequately produce and deliver milk to pups, suggesting that milk ejection is unaffected. Thus the present study suggests that a loss-of-function mutant of Cx43 with partial gap junction channel coupling conductance results in a less severe mammary gland phenotype, which may partially explain the lack of reported lactation defects associated with ODDD patients.

scholarly journals Postnatal uterine development in Inverdale ewe lambs

Reproduction ◽  
2008 ◽  
Vol 135 (3) ◽  
pp. 357-365 ◽  
Author(s):  
Kanako Hayashi ◽  
Anne R O'Connell ◽  
Jennifer L Juengel ◽  
Ken P McNatty ◽  
George H Davis ◽  
...  
Keyword(s):  
Uterine Horn ◽  
Wild Type ◽  
Endometrial Gland ◽  
Antral Follicles ◽  
Ewe Lambs ◽  
Large Numbers ◽  
Uterine Growth ◽  
Uterine Glands ◽  
Gland Development ◽  
Uterine Development

Postnatal development of the uterus involves, particularly, development of uterine glands. Studies with ovariectomized ewe lambs demonstrated a role for ovaries in uterine growth and endometrial gland development between postnatal days (PNDs) 14 and 56. The uterotrophic ovarian factor(s) is presumably derived from the large numbers of growing follicles in the neonatal ovary present after PND 14. The Inverdale gene mutation (FecXI) results in an increased ovulation rate in heterozygous ewes; however, homozygous ewes (II) are infertile and have ‘streak’ ovaries that lack normal developing of preantral and antral follicles. Uteri were obtained on PND 56 to determine whether postnatal uterine development differs between wild-type (++) and II Inverdale ewes. When compared with wild-type ewes, uterine weight of II ewes was 52% lower, and uterine horn length tended to be shorter, resulting in a 68% reduction in uterine weight:length ratio in II ewes. Histomorphometrical analyses determined that endometria and myometria of II ewes were thinner and intercaruncular endometrium contained 38% fewer endometrial glands. Concentrations of estradiol in the neonatal ewes were low and not different between ++ and II ewes, but II ewes had lower concentrations of testosterone and inhibin-α between PNDs 14 and 56. Receptors for androgen and activin were detected in the neonatal uteri of both ++ and II ewes. These results support the concept that developing preantral and/or antral follicles of the ovary secrete uterotrophic factors, perhaps testosterone or inhibin-α, that acts in an endocrine manner to stimulate uterine growth and endometrial gland development in the neonatal ewes.

scholarly journals Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose

2020 ◽  
Vol 105 (5) ◽  
pp. 1538-1551
Author(s):  
Angela Delaney ◽  
Rita Volochayev ◽  
Brooke Meader ◽  
Janice Lee ◽  
Konstantinia Almpani ◽  
...  
Keyword(s):  
Reproductive Function ◽  
Normal Breast ◽  
Breast Development ◽  
Reproductive Axis ◽  
Gnrh Neurons ◽  
Male Patients ◽  
And Function ◽  
Human Embryology ◽  
The Brain ◽  
Insight Into

Abstract Context The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed. Objective The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures. Methods We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients. Results All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient. Conclusions Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.

scholarly journals Behavioural significance of prolactin signalling in the central nervous system during pregnancy and lactation

Reproduction ◽  
2002 ◽  
pp. 497-506 ◽  
Author(s):  
DR Grattan
Keyword(s):  
Hormone Secretion ◽  
Maternal Brain ◽  
Pregnancy And Lactation ◽  
The Central Nervous System ◽  
Hypothalamic Function ◽  
And Function ◽  
Gland Development ◽  
The Brain ◽  
Behavioural Significance

The role of prolactin in the regulation of mammary gland development and function during pregnancy and lactation is well established. However, in addition, prolactin appears to have a much wider role in the physiology of lactation. There is widespread expression of prolactin receptors in the hypothalamus during lactation, indicative of a multi-faceted role for prolactin in regulating hypothalamic function. During pregnancy and lactation, the maternal brain undergoes structural and functional modification, allowing the establishment of appropriate behaviour to feed and nurture the offspring, to adjust to the nutritional and metabolic demands of milk production, and to maintain appropriate hormone secretion to allow milk synthesis, secretion and ejection. The coordination of such a range of neurobiological and neuroendocrine adaptations requires an endocrine signalling mechanism, capable of communicating the reproductive state to the brain. Evidence indicates that prolactin is part of this mechanism.

scholarly journals How ketamine helps to overcome depression

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Thu N Huynh ◽  
Eric Klann
Keyword(s):  
Nmda Receptors ◽  
Genetically Modified ◽  
Symptoms Of Depression ◽  
Genetically Modified Mice ◽  
The Brain

Genetically modified mice shed new light on how ketamine can target NMDA receptors in the brain to reduce the symptoms of depression.

Ultrastructure of developing visual cortical synapses in the cat superior colliculus

1991 ◽  
Vol 49 ◽  
pp. 156-157
Author(s):  
Caroline A. Miller ◽  
Laura L. Bruce
Keyword(s):  
Superior Colliculus ◽  
Phosphate Buffer ◽  
Receptive Fields ◽  
Visual Cortical Area ◽  
Cortical Synapses ◽  
Visual Cortical ◽  
And Function ◽  
Phosphate Buffered Saline ◽  
The Brain ◽  
Cat Superior Colliculus

The first visual cortical axons arrive in the cat superior colliculus by the time of birth. Adultlike receptive fields develop slowly over several weeks following birth. The developing cortical axons go through a sequence of changes before acquiring their adultlike morphology and function. To determine how these axons interact with neurons in the colliculus, cortico-collicular axons were labeled with biocytin (an anterograde neuronal tracer) and studied with electron microscopy.Deeply anesthetized animals received 200-500 nl injections of biocytin (Sigma; 5% in phosphate buffer) in the lateral suprasylvian visual cortical area. After a 24 hr survival time, the animals were deeply anesthetized and perfused with 0.9% phosphate buffered saline followed by fixation with a solution of 1.25% glutaraldehyde and 1.0% paraformaldehyde in 0.1M phosphate buffer. The brain was sectioned transversely on a vibratome at 50 μm. The tissue was processed immediately to visualize the biocytin.

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