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Human Reproduction Update Nov 2022To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones...
BACKGROUND
To provide the optimal milieu for implantation and fetal development, the female reproductive system must orchestrate uterine dynamics with the appropriate hormones produced by the ovaries. Mature oocytes may be fertilized in the fallopian tubes, and the resulting zygote is transported toward the uterus, where it can implant and continue developing. The cervix acts as a physical barrier to protect the fetus throughout pregnancy, and the vagina acts as a birth canal (involving uterine and cervix mechanisms) and facilitates copulation. Fertility can be compromised by pathologies that affect any of these organs or processes, and therefore, being able to accurately model them or restore their function is of paramount importance in applied and translational research. However, innate differences in human and animal model reproductive tracts, and the static nature of 2D cell/tissue culture techniques, necessitate continued research and development of dynamic and more complex in vitro platforms, ex vivo approaches and in vivo therapies to study and support reproductive biology. To meet this need, bioengineering is propelling the research on female reproduction into a new dimension through a wide range of potential applications and preclinical models, and the burgeoning number and variety of studies makes for a rapidly changing state of the field.
OBJECTIVE AND RATIONALE
This review aims to summarize the mounting evidence on bioengineering strategies, platforms and therapies currently available and under development in the context of female reproductive medicine, in order to further understand female reproductive biology and provide new options for fertility restoration. Specifically, techniques used in, or for, the uterus (endometrium and myometrium), ovary, fallopian tubes, cervix and vagina will be discussed.
SEARCH METHODS
A systematic search of full-text articles available in PubMed and Embase databases was conducted to identify relevant studies published between January 2000 and September 2021. The search terms included: bioengineering, reproduction, artificial, biomaterial, microfluidic, bioprinting, organoid, hydrogel, scaffold, uterus, endometrium, ovary, fallopian tubes, oviduct, cervix, vagina, endometriosis, adenomyosis, uterine fibroids, chlamydia, Asherman's syndrome, intrauterine adhesions, uterine polyps, polycystic ovary syndrome and primary ovarian insufficiency. Additional studies were identified by manually searching the references of the selected articles and of complementary reviews. Eligibility criteria included original, rigorous and accessible peer-reviewed work, published in English, on female reproductive bioengineering techniques in preclinical (in vitro/in vivo/ex vivo) and/or clinical testing phases.
OUTCOMES
Out of the 10 390 records identified, 312 studies were included for systematic review. Owing to inconsistencies in the study measurements and designs, the findings were assessed qualitatively rather than by meta-analysis. Hydrogels and scaffolds were commonly applied in various bioengineering-related studies of the female reproductive tract. Emerging technologies, such as organoids and bioprinting, offered personalized diagnoses and alternative treatment options, respectively. Promising microfluidic systems combining various bioengineering approaches have also shown translational value.
WIDER IMPLICATIONS
The complexity of the molecular, endocrine and tissue-level interactions regulating female reproduction present challenges for bioengineering approaches to replace female reproductive organs. However, interdisciplinary work is providing valuable insight into the physicochemical properties necessary for reproductive biological processes to occur. Defining the landscape of reproductive bioengineering technologies currently available and under development for women can provide alternative models for toxicology/drug testing, ex vivo fertility options, clinical therapies and a basis for future organ regeneration studies.
Topics: Animals; Female; Humans; Pregnancy; Bioengineering; Embryo Implantation; Genitalia, Female; Reproduction; Uterus
PubMed: 35652272
DOI: 10.1093/humupd/dmac025 -
Nature Sep 2021Transient neuromodulation can have long-lasting effects on neural circuits and motivational states. Here we examine the dopaminergic mechanisms that underlie mating...
Transient neuromodulation can have long-lasting effects on neural circuits and motivational states. Here we examine the dopaminergic mechanisms that underlie mating drive and its persistence in male mice. Brief investigation of females primes a male's interest to mate for tens of minutes, whereas a single successful mating triggers satiety that gradually recovers over days. We found that both processes are controlled by specialized anteroventral and preoptic periventricular (AVPV/PVpo) dopamine neurons in the hypothalamus. During the investigation of females, dopamine is transiently released in the medial preoptic area (MPOA)-an area that is critical for mating behaviours. Optogenetic stimulation of AVPV/PVpo dopamine axons in the MPOA recapitulates the priming effect of exposure to a female. Using optical and molecular methods for tracking and manipulating intracellular signalling, we show that this priming effect emerges from the accumulation of mating-related dopamine signals in the MPOA through the accrual of cyclic adenosine monophosphate levels and protein kinase A activity. Dopamine transients in the MPOA are abolished after a successful mating, which is likely to ensure abstinence. Consistent with this idea, the inhibition of AVPV/PVpo dopamine neurons selectively demotivates mating, whereas stimulating these neurons restores the motivation to mate after sexual satiety. We therefore conclude that the accumulation or suppression of signals from specialized dopamine neurons regulates mating behaviours across minutes and days.
Topics: Animals; Copulation; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dopamine; Dopaminergic Neurons; Drive; Female; Hypothalamus; Male; Mice; Optogenetics; Preoptic Area; Satiety Response; Sexual Behavior, Animal; Signal Transduction; Time Factors
PubMed: 34433964
DOI: 10.1038/s41586-021-03845-0 -
Nature Jan 2021Animal behaviours that are superficially similar can express different intents in different contexts, but how this flexibility is achieved at the level of neural...
Animal behaviours that are superficially similar can express different intents in different contexts, but how this flexibility is achieved at the level of neural circuits is not understood. For example, males of many species can exhibit mounting behaviour towards same- or opposite-sex conspecifics, but it is unclear whether the intent and neural encoding of these behaviours are similar or different. Here we show that female- and male-directed mounting in male laboratory mice are distinguishable by the presence or absence of ultrasonic vocalizations (USVs), respectively. These and additional behavioural data suggest that most male-directed mounting is aggressive, although in rare cases it can be sexual. We investigated whether USV and USV mounting use the same or distinct hypothalamic neural substrates. Micro-endoscopic imaging of neurons positive for oestrogen receptor 1 (ESR1) in either the medial preoptic area (MPOA) or the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) revealed distinct patterns of neuronal activity during USV and USV mounting, and the type of mounting could be decoded from population activity in either region. Intersectional optogenetic stimulation of MPOA neurons that express ESR1 and vesicular GABA transporter (VGAT) (MPOA neurons) robustly promoted USV mounting, and converted male-directed attack to mounting with USVs. By contrast, stimulation of VMHvl neurons that express ESR1 (VMHvl neurons) promoted USV mounting, and inhibited the USVs evoked by female urine. Terminal stimulation experiments suggest that these complementary inhibitory effects are mediated by reciprocal projections between the MPOA and VMHvl. Together, these data identify a hypothalamic subpopulation that is genetically enriched for neurons that causally induce a male reproductive behavioural state, and indicate that reproductive and aggressive states are represented by distinct population codes distributed between MPOA and VMHvl neurons, respectively. Thus, similar behaviours that express different internal states are encoded by distinct hypothalamic neuronal populations.
Topics: Aggression; Animals; Copulation; Estrogen Receptor alpha; Female; Homosexuality, Male; Hypothalamus; Male; Mice; Optogenetics; Preoptic Area; Sexual Behavior, Animal; Vesicular Inhibitory Amino Acid Transport Proteins
PubMed: 33268894
DOI: 10.1038/s41586-020-2995-0 -
Annual Review of Entomology Jan 2023Mating produces profound changes in the behavior of female flies, such as an increase in oviposition, reduction in sexual receptivity, increase in feeding, and even... (Review)
Review
Mating produces profound changes in the behavior of female flies, such as an increase in oviposition, reduction in sexual receptivity, increase in feeding, and even excretion. Many of these changes are produced by copulation, sperm, and accessory gland products that males transfer to females during mating. Our knowledge on the function of the male ejaculate and its effect on female insects is still incipient. In this article, we review peri- and postcopulatory behaviors in tephritid flies. We address the effects of male copulatory behavior; copula duration; and the male ejaculate, sperm, and accessory gland products on female remating behavior. Many species from these families are pests of economic importance; thus, understanding male mating effects on female behavior contributes to both developing more effective environmentally friendly control methods and furthering our understanding of evolutionary implications of intersexual competition and sexual conflict.
Topics: Male; Female; Animals; Diptera; Semen; Spermatozoa; Copulation; Sexual Behavior, Animal
PubMed: 36198400
DOI: 10.1146/annurev-ento-120220-113618 -
Philosophical Transactions of the Royal... Dec 2020Aggressive and cannibalistic female spiders can impose strong selection on male mating and fertilization strategies. Furthermore, the distinctive reproductive morphology... (Review)
Review
Aggressive and cannibalistic female spiders can impose strong selection on male mating and fertilization strategies. Furthermore, the distinctive reproductive morphology of spiders is predicted to influence the outcome of sperm competition. Polyandry is common in spiders, leading to defensive male strategies that include guarding, plugging and self-sacrifice. Paternity patterns are highly variable and unlikely to be determined solely by mating order, but rather by relative copulation duration, deployment of plugs and cryptic female choice. The ability to strategically allocate sperm is limited, either by the need to refill pedipalps periodically or owing to permanent sperm depletion after mating. Further insights now rely on unravelling several proximate mechanisms such as the process of sperm activation and the role of seminal fluids. This article is part of the theme issue 'Fifty years of sperm competition'.
Topics: Animals; Cannibalism; Copulation; Male; Reproduction; Sexual Behavior, Animal; Spermatozoa; Spiders
PubMed: 33070729
DOI: 10.1098/rstb.2020.0073 -
Revista Chilena de Infectologia :... Feb 2020We remember Lazaro Spallanzani (1729-1799) mainly for his controversy with Needham over spontaneous generation, but he was a man of multiple scientific activities in the... (Review)
Review
We remember Lazaro Spallanzani (1729-1799) mainly for his controversy with Needham over spontaneous generation, but he was a man of multiple scientific activities in the fields of biology, mineralogy, physics, mathematics and… volcanology! Called "the biologist of biologists", he developed a series of investigations about reproduction of amphibian, in one of them -Experiences in service to the history of the generation of animals and plants- we have found horrific experiments with frogs, including severe and useless mutilation of males, in order to interrupt its copulation with females, acts he describes as "barbaric", and we estimate inadmissible in the ecclesiastic man he was, even in an epoch in which animals were considered "anima vili" (something without value). A brief review of the use of animals in laboratories shows significant advances in the ethical regulations for this practice, but we believe that these achievements are not enough.
Topics: Animal Welfare; Animals; Animals, Laboratory; Female; History, 18th Century; Laboratories; Male; Reproduction; Science
PubMed: 32730402
DOI: 10.4067/S0716-10182020000100064 -
Nature May 2021Innate social behaviours, such as mating and fighting, are fundamental to animal reproduction and survival. However, social engagements can also put an individual at...
Innate social behaviours, such as mating and fighting, are fundamental to animal reproduction and survival. However, social engagements can also put an individual at risk. Little is known about the neural mechanisms that enable appropriate risk assessment and the suppression of hazardous social interactions. Here we identify the posteromedial nucleus of the cortical amygdala (COApm) as a locus required for the suppression of male mating when a female mouse is unhealthy. Using anatomical tracing, functional imaging and circuit-level epistatic analyses, we show that suppression of mating with an unhealthy female is mediated by the COApm projections onto the glutamatergic population of the medial amygdalar nucleus (MEA). We further show that the role of the COApm-to-MEA connection in regulating male mating behaviour relies on the neuromodulator thyrotropin-releasing hormone (TRH). TRH is expressed in the COApm, whereas the TRH receptor (TRHR) is found in the postsynaptic MEA glutamatergic neurons. Manipulating neural activity of TRH-expressing neurons in the COApm modulated male mating behaviour. In the MEA, activation of the TRHR pathway by ligand infusion inhibited mating even towards healthy female mice, whereas genetic ablation of TRHR facilitated mating with unhealthy individuals. In summary, we reveal a neural pathway that relies on the neuromodulator TRH to modulate social interactions according to the health status of the reciprocating individual. Individuals must balance the cost of social interactions relative to the benefit, as deficits in the ability to select healthy mates may lead to the spread of disease.
Topics: Amygdala; Animals; Copulation; Corticomedial Nuclear Complex; Female; Glutamic Acid; Health; Ligands; Lipopolysaccharides; Male; Mating Preference, Animal; Mice; Neural Pathways; Neurons; Receptors, Thyrotropin-Releasing Hormone; Social Behavior; Thyrotropin-Releasing Hormone
PubMed: 33790466
DOI: 10.1038/s41586-021-03413-6 -
Theory in Biosciences = Theorie in Den... Jun 2020The aim of the paper is to identify psychosomatic evolutionary adaptations of hominids, which direct them at maximizing their reproductive success, and on the basis of...
The aim of the paper is to identify psychosomatic evolutionary adaptations of hominids, which direct them at maximizing their reproductive success, and on the basis of which their various social structures are built. Selected features of the hominid last common ancestor were extracted; by reducing the influence of the social structure, they were defined as the hominid "sexual nature"; these considerations were supported by the analysis of sexual jealousy as a function of socio-environmental conditions. The "sexuality core" of a hominid female was defined as "selective polyandry"-the female selects the best males among those available; and of a hominid male as "tolerant promiscuity"-the male strives for multi-male and multi-female copulations with sexually attractive females. The extracted "sexuality cores" condemn hominids to a patriarchal social structure and thus to sexual coercion and jealousy. The source of male sexual jealousy is limited access to females. Hominid female jealousy of the male results mainly from the need for protection and support. Hominids' social structures are determined by females' sexual selectivity or opportunism and by their continuous or periodic proceptivity and estrus signaling. Evolutionary functions developed by women: out-estrus sexuality, copulation calls, multiple orgasms, allow them to obtain the best possible spermatozoid. The institution of marriage blocks the influence of sexual selection in the species Homo sapiens.
Topics: Animals; Biological Evolution; Copulation; Female; Hominidae; Humans; Hylobates; Jealousy; Macaca; Male; Models, Biological; Models, Theoretical; Pan troglodytes; Papio; Reproduction; Sexual Behavior; Sexual Behavior, Animal; Sexuality
PubMed: 32170558
DOI: 10.1007/s12064-020-00312-8 -
Current Biology : CB Oct 2022Most vertebrates, including all mammals and birds, are sexually reproducing organisms. The implication of sexual reproduction is that an adult bird exists because a male...
Most vertebrates, including all mammals and birds, are sexually reproducing organisms. The implication of sexual reproduction is that an adult bird exists because a male transferred sperm to the reproductive tract of a female during copulation, one of the sperm fertilized an egg, and the ensuing embryo developed into an individual male or female that in turn can reproduce. This fundamental feature of sexual life - the need to bring together male and female units (genomes, gametes, individuals) in a sequence of interactions - is both fascinating and fraught with conflict, because selection acts on individuals to maximize their own lifetime reproductive success (or on individual units of DNA to maximize the number of copies of themselves that remain in the gene pool). As a consequence, a bewildering diversity of reproductive traits and behaviours has evolved.
Topics: Humans; Animals; Male; Female; Semen; Reproduction; Copulation; Birds; Spermatozoa; Mammals; Sexual Behavior, Animal
PubMed: 36283376
DOI: 10.1016/j.cub.2022.06.066 -
Addiction Biology Sep 2021Alcohol-induced aggression is a destructive and widespread phenomenon associated with violence and sexual assault. However, little is understood concerning its...
Alcohol-induced aggression is a destructive and widespread phenomenon associated with violence and sexual assault. However, little is understood concerning its mechanistic origin. We have developed a Drosophila melanogaster model to genetically dissect and understand the phenomenon of sexually dimorphic alcohol-induced aggression. Males with blood alcohol levels of 0.04-mg/ml BAC were less aggressive than alcohol-naive males, but when the BAC had dropped to ~0.015 mg/ml, the alcohol-treated males showed an increase in aggression toward other males. This aggression-promoting treatment is referred to as the post-ethanol aggression (PEA) treatment. Females do not show increased aggression after the same treatment. PEA-treated males also spend less time courting and attempt to copulate earlier than alcohol-naive flies. PEA treatment induces expression of the FruM transcription factor (encoded by a male-specific transcript from the fruitless gene), whereas sedating doses of alcohol reduce FruM expression and reduce male aggression. Transgenic suppression of FruM induction also prevents alcohol-induced aggression. In male flies, alcohol-induced aggression is dependent on the male isoform of the fruitless transcription factor (FruM). Low-dose alcohol induces FruM expression and promotes aggression, whereas higher doses of alcohol suppress FruM and suppress aggression.
Topics: Aggression; Animals; Drosophila melanogaster; Ethanol; Female; Gene Expression Regulation; Male; Nerve Tissue Proteins; Neurons; Sex Characteristics; Sexual Behavior, Animal; Transcription Factors
PubMed: 34044470
DOI: 10.1111/adb.13045