Hanne M Hoffmann

• PhD
• Professor (Associate) at Michigan State University

Management of labor in women with diabetes is challenging due to the high risk of complications during labor and postpartum. To avoid cesarian section and assist with labor progression, Pitocin, a synthetic oxytocin, is frequently used to induce and augment labor. However, the efficacy of Pitocin is often compromised in diabetic pregnancies, leadin...

BACKGROUND: Spontaneous labor and birth peak during the late evening and early morning hours, indicating an endogenous rhythm in labor onset and birth. We hypothesize that the time-of-day of labor induction will define labor duration and the risk of cesarian section. METHODS: In a retrospective study of pregnant women who were induced for labor (n...

Disclosure: J.S. Lee: None. A.M. Yaw: None. H.M. Hoffmann: None. Introduction: The placenta serves as an interface facilitating the exchange of essential nutrients and oxygen between the mother and fetus. Preeclampsia, a complication of pregnancy driven by placental dysfunction, is one of the leading causes of maternal, fetal, and neonatal morbidit...

Disclosure: A.M. Yaw: None. M.E. Gardella: None. J. Jacobs: None. H.M. Hoffmann: None. Millions of cats enter animal shelters each year. Unfortunately, due to high numbers of cats entering shelters and limited physical housing space, over 50% of healthy and adoptable cats with extended shelter stays are euthanized yearly. While animal shelters are...

Background The suprachiasmatic nucleus (SCN) within the hypothalamus is a key brain structure required to relay light information to the body and synchronize cell and tissue level rhythms and hormone release. Specific subpopulations of SCN neurons, defined by their peptide expression, regulate defined SCN output. Here we focus on the vasoactive int...

Life on earth has evolved under a consistent cycle of light and darkness caused by the earth's rotation around its axis. This has led to a 24-hour circadian system in most organisms, ranging all the way from fungi to humans. With the advent of electric light in the 19th century, cycles of light and darkness have drastically changed. Shift workers a...

Disclosure: J.S. Lee: None. H.M. Hoffmann: None. Introduction Pre-eclampsia is one of the leading causes of maternal, fetal, and neonatal morbidity and mortality, complicating about 4% of pregnancies. Recent work has identified PERIOD3 (PER3), a gene regulating 24-hour circadian rhythms, to be downregulated in the preeclamptic placenta. The role of...

Long non-coding RNAs (lncRNAs) have a much higher cell- and/or tissue-specificity compared to mRNAs in most cases, making them excellent candidates for therapeutic applications to reduce off-target effects. Placental long non-coding RNAs have been investigated in the pathogenesis of preeclampsia (often causing preterm birth (PTB)), but less is know...

Obesity impacts fertility and is positively correlated with endometrial hyperplasia and endometrial cancer occurrence. Endometrial epithelia often harbor disease driver-mutations, while endometrial stroma are highly regulative of neighboring epithelia. Here, we sought to determine distinct transcriptome changes occurring in individual cell types in...

Pre-eclampsia (PE) is a hypertensive condition that occurs during pregnancy and complicates up to 4% of pregnancies. PE exhibits several circadian-related characteristics, and the placenta possesses a functioning molecular clock. We examined the associations of 17 core circadian gene transcripts in placenta with PE vs. non-PE (a mixture of pregnant...

A hormone enhances cognition in mouse models of Alzheimer's disease and Down syndrome.

In women, excess androgen causes polycystic ovary syndrome (PCOS), a common fertility disorder with comorbid metabolic dysfunctions including diabetes, obesity, and nonalcoholic fatty-liver disease (NAFLD). Using a PCOS mouse model, this study shows that chronic high androgen levels cause hepatic steatosis while hepatocyte-specific androgen recepto...

For 3.5 billion years before electric light was invented in 1879, life on Earth evolved under the pattern of light during the day and darkness during the night. Through evolution, nearly all organisms internalized the temporal rhythm of Earth’s 24-hour rotation and evolved self-sustaining biological clocks with a ~24-hour rhythm. These internal rhy...

Objective The increasing prevalence of obesity makes it important to increase understanding of the maturation and function of the neuronal integrators and regulators of metabolic function. Methods Behavioral, molecular, and physiological analyses of transgenic mice with Sine oculis 3 (Six3) deleted in mature neurons using the Synapsincre allele....

The homeodomain transcription factors sine oculis homeobox 3 (Six3) and ventral anterior homeobox 1 (Vax1) are required for brain development. Their expression in specific brain areas is maintained in adulthood, where their functions are poorly understood. To identify the roles of Six3 and Vax1 in neurons, we conditionally deleted each gene using S...

Previous studies have observed an association between maternal circadian rhythm disruption and preterm birth (PTB). However, the underlying molecular mechanisms and the potential of circadian clock genes to serve as predictors of PTB remain unexplored. We examined the association of 10 core circadian transcripts in maternal blood with spontaneous P...

Regulation of Kiss1 transcription is crucial to the development and function of the reproductive axis. The homeodomain transcription factor, ventral anterior homeobox 1 (VAX1), has been implicated as a potential regulator of Kiss1 transcription. However, it is unknown whether VAX1 directly mediates transcription within kisspeptin neurons or works i...

Approximately 21 million Americans are employed in nighttime or rotating shiftwork, which is linked with numerous health risks, including reduced reproductive success. While there is a strong body of clinical evidence associating shift workers with deficits in fertility, very little is known about the mechanisms by which shiftwork produces reproduc...

Light provides the primary timing signal that enables fine-tuned behavioral and hormonal entrainment of circadian rhythms to the environment. Light is transmitted from the eye to the brain through the retinohypothalamic tract, where one target is the hypothalamic suprachiasmatic nucleus (SCN), which generates self-sustained circadian rhythms. The v...

Caesarian section should be avoided unless medically required. Caesarian section is often a result of failed labor enhancement. While most natural births occur at night, labor enhancement is often scheduled during the day. We propose that the disparity between the commonly used timing of labor enhancement in the clinic, from the timing of natural b...

Shiftwork, including work that takes place at night (nightshift) and/or rotates between day and nightshifts, plays an important role in our society, but is associated with decreased health, including reproductive dysfunction. One key factor in shiftwork, exposure to light at night, has been identified as a likely contributor to the underlying healt...

Different subtypes of interneurons, destined for the olfactory bulb, are continuously generated by neural stem cells located in the ventricular and subventricular zones along the lateral forebrain ventricles of mice. Neuronal identity in the olfactory bulb depends on the existence of defined microdomains of pre-determined neural stem cells along th...

Different subtypes of interneurons, destined for the olfactory bulb, are continuously generated by neural stem cells located in the ventricular and subventricular zones along the lateral forebrain ventricles of mice. Neuronal identity in the olfactory bulb depends on the existence of defined microdomains of pre-determined neural stem cells along th...

Different subtypes of interneurons, destined for the olfactory bulb, are continuously generated by neural stem cells located in the ventricular and subventricular zones along the lateral forebrain ventricles of mice. Neuronal identity in the olfactory bulb depends on the existence of defined microdomains of pre-determined neural stem cells along th...

Molecular and behavioral timekeeping is regulated by the circadian system represented on the cellular level by clock transcription factors, including Period2 (PER2), Bmal1, Clock and Cry. These transcription factors drive a daily ~24h rhythm in gene expression leading to tissue specific receptor expression optimizing sensitivity to hormones and dru...

Several subtypes of interneurons destined for the olfactory bulb are continuously generated after birth by neural stem cells located in the ventricular-subventricular zones of the lateral ventricles. Future neuronal identity depends on the positioning of pre-determined neural stem cells along the ventricle walls, which, in turn, depends on delimite...

Molecular and behavioral timekeeping is regulated by the circadian system which includes the brain's suprachiasmatic nucleus (SCN) that translates environmental light information into neuronal and endocrine signals aligning peripheral tissue rhythms to the time of day. Despite the critical role of circadian rhythms in fertility, it remains unexplor...

The brain’s primary circadian pacemaker, the suprachiasmatic nucleus (SCN), is required to translate day-length and circadian rhythms into neuronal, hormonal, and behavioral rhythms. Here, we identify the homeodomain transcription factor ventral anterior homeobox 1 (Vax1) as required for SCN development, vasoactive intestinal peptide expression, an...

Many physiological systems rely on hormones to communicate and time cellular and tissue-level functions. Most endocrine systems are dynamic and governed by complex regulatory systems and/or feedback mechanisms to generate precise patterns and modes of hormone release in order to optimize control of physiological and cellular processes. This Special...

Precise timing in hormone release from the hypothalamus, the pituitary and ovary is critical for fertility. Hormonal release patterns of the reproductive axis are regulated by a feedback loop within the hypothalamic-pituitary-gonadal (HPG) axis. The timing and rhythmicity of hormone release and tissue sensitivity in the HPG axis is regulated by cir...

Hypothalamic gonadotropin-releasing hormone (GnRH; LHRH) neurons are crucial for the hypothalamic-pituitary-gonadal (HPG) axis that regulates mammalian fertility. Insufficient GnRH disrupts the HPG axis and is often associated with the genetic condition idiopathic hypogonadotropic hypogonadism (IHH). The homeodomain protein sine oculis-related home...

In women, excess androgen causes polycystic ovarian syndrome (PCOS), a common fertility disorder with comorbid metabolic dysfunction. A growing body of evidence show that non-alcoholic fatty liver disease (NAFLD) rates are elevated in PCOS women, with higher risk of developing more severe forms of NAFLD. PCOS is a complex condition encompassing ins...

Increasingly, studies utilize cell-specific deletion of genes through conditional gene deletion by CRE recombination. Despite numerous advantages, this strategy also has limits such as ectopic CRE-expression and germline recombination. Two commonly used gonadotropin-releasing hormone (Gnrh)-driven CRE-expressing mice both target GnRH neurons. Howev...

Mating behavior in males and females is dependent on olfactory cues processed through both the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). Signaling through the MOE is critical for the initiation of male mating behavior, and the loss of MOE signaling severely compromises this comportment. Here, we demonstrate that dosage of the...

Assessment of reproductive competence is critical for understanding the impact of a treatment or genetic manipulation on the reproductive axis, also termed the hypothalamic-pituitary-gonadal axis. The reproductive axis is a key integrator of environmental and internal input adapting fertility to favorable conditions for reproduction. Prior to embar...

Haploinsufficiency occurs when loss of one copy of a diploid gene (hemizygosity) causes a phenotype. It is relatively rare, in that most genes can produce sufficient mRNA and protein from a single copy to prevent any loss of normal activity and function. Reproduction is a complex process relying on migration of GnRH neurons from the olfactory placo...

Study of transcriptional regulation of the gonadotropin-releasing hormone gene, Gnrh1, is of importance due to the key role of GnRH in maintaining fertility through its regulation of gonadotrope cells in the anterior pituitary. Absence of GnRH impairs puberty and leads to complete infertility due to disruption of the reproductive axis. The importan...

Background Proper expression of key reproductive hormones from gonadotrope cells of the pituitary is required for pubertal onset and reproduction. To further our understanding of the molecular events taking place during embryonic development, leading to expression of the glycoproteins luteinizing hormone (LH) and follicle-stimulating hormone (FSH),...

Link to free version of this paper: https://authors.elsevier.com/a/1WPOv153jzTqES Gonadotropin-releasing hormone (GnRH) is required for pubertal onset and reproduction, thus the control of GnRH transcription is tightly regulated during development and adulthood. GnRH neuron development depends on transcription factors of the homeodomain family. Fo...

Background: Cocaine addiction continues to be a major heath concern, and despite public health intervention there is a lack of efficient pharmacological treatment options. A newly identified potential target are the group I metabotropic glutamate receptors (mGluR1/5), with allosteric modulators showing particular promise. Methods: We evaluated t...

Fertility depends on the correct maturation and function of approximately 800 gonadotropin-releasing hormone (GnRH) neurons in the brain. GnRH neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates fertility. In adulthood, GnRH neurons are scattered throughout the anterior hypothalamic area and project to the median emine...

Fertility depends on the correct maturation and function of approximately 800 gonadotropin-releasing hormone (GnRH) neurons in the brain. GnRH neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates fertility. In adulthood, GnRH neurons are scattered throughout the anterior hypothalamic area and project to the median emine...

Unlabelled: Hypothalamic gonadotropin-releasing hormone (GnRH) neurons are at the apex of the hypothalamic-pituitary-gonadal axis that regulates mammalian fertility. Herein we demonstrate a critical role for the homeodomain transcription factor ventral anterior homeobox 1 (VAX1) in GnRH neuron maturation and show that Vax1 deletion from GnRH neuro...

SIX3 and SIX6, two closely related homeodomain transcription factors, are involved in development of the mammalian neuroendocrine system and mutations of Six6 adversely affect fertility in mice. We show that both siRNA knockdown in gonadotrope cell lines and knockout of Six6 in both embryonic and adult male mice (Six6-KO) support roles for SIX3 and...

The known genetic causes of idiopathic hypogonadotropic hypogonadism (IHH) are often associated with the loss of gonadotropin-releasing hormone (GnRH) neurons leading to disruption of the hypothalamic pituitary gonadal axis and subfertility. The majority of IHH cases have unknown origins and likely arise from compound mutations in more than one gen...

The general effects of cocaine are not well understood at the molecular level. What is known is that the dopamine D1 receptor plays an important role. Here we show that a key mechanism may be cocaine's blockade of the histamine H3 receptor-mediated inhibition of D1 receptor function. This blockade requires the σ1 receptor and occurs upon cocaine bi...

Histamine H3 receptors (H3R) are widely expressed in the brain where they participate in sleep–wake cycle and cognition among other functions. Despite their high expression in some regions of the basal ganglia, their functional role in this forebrain neural network remains unclear. The present findings provide in situ hybridization and immunohistoc...

Kisspeptin signaling through its receptor, Kiss1R, is crucial for many reproductive functions including puberty, sex steroid feedback, and overall fertility. While the importance of Kiss1R in the brain is firmly established, its role in regulating reproduction at the level of the pituitary is not well understood. This study presents molecular analy...

Cocaine abuse leads to adaptations in brain reward circuits, where dopaminergic neurotransmission is a fundamental component. We hypothesized that chronic cocaine self-administration could influence dopamine D1 and D2 receptor activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) and cyclic adenosine monophosphate response el...

Previously, using artificial cell systems, we identified receptor heteromers between the dopamine D1 or D2 receptors and the histamine H3 receptor. In addition, we demonstrated two biochemical characteristics of the dopamine D1 receptor-histamine H3 receptor heteromer. We have now extended this work to show the dopamine D1 receptor-histamine H3 rec...

Previously, using artificial cell systems, we identified receptor heteromers between the dopamine D1 or D2 receptors and histamine H3 receptor. In addition we demonstrated two biochemical characteristics of the dopamine D1 receptor-histamine H3 receptor heteromer. We have now extended this work to show the dopamine D1 receptor-histamine H3 receptor...

G protein-coupled receptor (GPCR) heteromers are macromolecular complexes with unique functional properties different from those of its individual protomers. Little is known about what determines the quaternary structure of GPCR heteromers resulting in their unique functional properties. In this study, using resonance energy transfer techniques in...