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Genom åren har det funnits en marknad för att förhindra samt öka chanserna att bli gravid. Individer har vänt sig till appar för hjälp, där syftet har varit att öka individenskunskap om när fertilitetfönstret sker under cyklens gång. Fertilitetfönstret kan upptäckas genom olika metoder. Under studiens gång las fokus på att bygga uppförståelse för basal kroppstemperatur. Därefter vidareutvecklades en smart tandborste integrerat med en temperature sensor, med syftet att kunna identifiera korrelation mellan basal kroppstemperatur och ägglossning. Syftet var att undersöka om en smart tandborste integrerat med en temperatur sensor, kunde identifiera potential ägglossning. Identifiering kunde skapas genom finna den potentiella sambandet mellan basal kroppstemperatur och ägglossning. Produktenskapades genom användning av maskininlärningsteknik. Det uppsatta syftet svaradepå forskningsfrågorna; kan maskininlärningstekniker stödja förutsägelse av ägglossning från basal kroppstemperatur (förkortning Eng: BBT) med en smart tandborste och hur ska en temperatursensor integreras i en elektrisk tandborste? Fördjupningsarbetet delades in i tre delar, undersökning av basal kroppstemperatur, data analys och produktdesign. En litteraturstudie utfördes av alla delar där undersökning om vilka likheter kroppstemperatur har mot basal kroppstemperatur, hur data analys kan användas till att upptäcka ägglossning med basal kroppstemperatur, och hur en produkt kan bäst designas för målen i arbetet. Före påbörjandet av examensarbete, samlades 11 individers basal kroppstemperatur in. Den valda metoden för att vidare analysera den givna data kallas för k-means clustering. Underdataanalysen ändrades antalet grupperingar för att finna grupper där potentiell ägglossning kunde ha uppstått. Validering av dessa potentiella grupper gjordes med data hämtat från hemsidan my monthly cycle. För produktutveckling användes flera olika tekniker, för att vägleda samt analysera produkten från olika perspektiv. Genom noggrann mätning av kroppstemperatur kunde den basala kroppstemperaturen uppskattas, med en okänd noggrannhet. Kluster av den för-insamlade dataformades och visade att vissa grupper kunde tolkas ha potential till ägglossning. Dessa potentiella grupper kunde valideras till att ha majoriteten av ägglossningsdata tilldelat till dem när färre grupperingar gjordes. En optimal prototyp skapades med hänsyn på hållbarhet, och bekvämlighet, både för bruk och minskning av sysslor. Sammanfattningsvis visade användning av klusteranalys ha en potentiell möjlighetför att kunna detektera ägglossning hos kroppstemperatur data som samlas in med en smart tandborste. För framtida forskning bör en tandborstdesign först skapas för att samla in basal kroppstemperatur data, där följaktligen blir att använda den insamlade datan till data analysen

The goal of this long-term study was to better understand the reproductive biology of the female bottlenose dolphin (Tursiops truncatus) and provide a hypothesis for how dolphins may communicate reproductive readiness to one another. Utilizing conditioned dolphins in aquaria, this dissertation examined several previously unknown aspects of dolphin reproduction, including ovarian follicular dynamics during the luteinizing hormone surge, urinary prolactin levels, estrus behavior, vaginal fluid arboriform arrangement, in-situ vaginal and cervical anatomy during estrus, reversed-phase high-performance liquid chromatography (RP-HPLC) of urine samples to identify proteins and peptides that may be used in chemical communication, and a review and anatomical analysis of dolphin vibrassal crypts. The diffusely seasonal dolphin estrous cycle is not controlled by photoperiod and has a 10-day follicular and 20-day luteal phase. A brief ovulatory LH surge is followed by ovulation within 48 hours. An ethogram of 20 reproductive behaviors was developed, and all occurrences of reproductive behavior were analyzed during conceptive estrous cycles. A novel form of standing heat estrus, termed immobility, was observed, and estrus dolphins displayed genital nuzzling, active and passive mounting with other females, and an increase of standing heat intensity as LH levels rose. Prolactin plays a role in pregnancy maintenance, mammary development, allo-mothering behavior, lactation, and lactational anestrus. Dolphins are similar to sows where weaning causes a return to estrus, and in the boar effect, where days to ovulation are shortened in the presence of a mature male. Dolphin vaginal fluid showed crystallization arrangements with large open mesh patterns, conducive to sperm transport, during the estrogenic follicular phase, and closed mesh during the luteal phase. RP-HPLC analysis revealed that urine contained large amounts of peptides and proteins with peaks that change throughout the estrous cycle and with changes in social grouping. Remnant vibrissae from dolphin follicular crypts were sectioned, and it was hypothesized that trigeminal nerve endings could act similarly to those found in the nasal mucosa of terrestrial species and respond to chemical stimuli. This study provides new data to better understand the reproductive biology of a holaquatic mammal.

L’ovaire est un organe indispensable à la fonction reproductive, car il permet la production, la maturation et la libération de la cellule germinale femelle, l’ovocyte. Malgré son rôle central dans la régulation de la reproduction chez la femme, plusieurs de ses processus physiologiques et de ses conditions pathologiques sont encore imparfaitement décrits. La caractérisation du rôle de nouveaux régulateurs pourrait permettre l’élucidation de plusieurs questionnements actuels en physiologie ovarienne. Initialement étudiée dans l’organogenèse et l’oncogenèse pour son implication dans la prolifération, la migration, la différenciation et l’apoptose cellulaire, la voie de signalisation Hippo pourrait s’avérer être un facteur déterminant dans la physiologie ovarienne. En effet, elle a été récemment rapportée comme participant à la régulation de l’activation folliculaire, de la prolifération des cellules de la granulosa et de l’ovulation. La voie Hippo consiste en une cascade de kinases menant ultimement à la phosphorylation des deux co-régulateurs transcriptionnels YAP1 (yes-associated protein 1) et TAZ (transcriptional coactivator with a PDZ-binding motif). L’objectif général de ce projet de thèse était de caractériser les rôles de Yap1/Taz dans la physiologie ovarienne en utilisant des modèles murins transgéniques d’inactivation conditionnelle de ces gènes dans les cellules de la granulosa. La première portion du projet a conduit à la caractérisation d’un phénotype inattendu de défaut des oviductes. Les souris femelles adultes étaient sous-fertiles et leur fonction ovarienne était intacte. En fait, la sous-fertilité était causée par le piégeage des embryons dans des dilatations de la paroi de l’oviducte, empêchant ainsi leur transport adéquat vers l’utérus. Nous sommes parvenus à démontrer que la perte d’expression de YAP1/TAZ dans les couches musculeuses de l’oviducte conduisait à un amincissement progressif de sa paroi et était ultimement responsable de l’échec du transport embryonnaire. Dans la seconde portion du projet, nous avons utilisé la culture primaire de cellules de la granulosa afin de décrire l’implication de la voie Hippo dans l’ovulation. Nous avons identifié la protéine kinase A comme modulateur clé de l’activation de la voie Hippo par l’hormone lutéinisante (LH). En utilisant un système adénoviral de délétion de Yap1/Taz, nous avons mis en évidence l’importance de leur expression pour l’induction de plusieurs gènes cibles de la LH. Ensuite, au moyen d’une expérience d’immunoprécipitation de la chromatine, nous avons démontré l’implication de YAP1 dans la régulation de la transcription de l’amphiréguline, un effecteur central de la cascade de signalisation de la LH. Dans son ensemble, ce projet a permis de mettre la lumière sur de nouveaux rôles de la voie de signalisation Hippo dans la régulation des cellules musculaires lisses de l’oviducte et des cellules de la granulosa durant l’ovulation chez la souris. Elles ouvrent la voie à une investigation plus précise de l’implication de la voie Hippo dans ces deux organes clés du système reproducteur femelle. / The ovary is a central organ of the female reproductive tract involved in oocyte production, maturation and release. Still, many physiological and pathological ovarian processes remain to be described more comprehensively. The precise characterization of the roles of new ovarian regulators would contribute to a better understanding of its physiology. The Hippo signaling pathway was initially studied for its roles in cellular proliferation, apoptosis, migration and differentiation during organ and tumor development. Recently, it has been shown to be involved during normal physiological processes of multiple organs, including the ovary. Hippo was shown to be involved in the activation of primordial follicles, in the proliferation of granulosa cells and during ovulation. Hippo consists of a central kinase cascade leading to the phosphorylation of YAP1 (yes-associated protein 1) and TAZ (transcriptional coactivator with a PDZ-binding motif), the two transcriptional coactivators of the pathway. The objective of this thesis was to characterize the precise roles of Yap1/Taz in ovarian physiology using transgenic mouse models of their genetic deletion in granulosa cells. The first part of this thesis project led to the characterization of an unexpected oviductal phenotype. Adult females were subfertile and their ovarian function was unaffected. The subfertility was rather caused by the entrapment of embryos in oviductal dilations, preventing their normal transport to the uterus. We demonstrated that loss of YAP1/TAZ expression in oviductal smooth muscle cells led to a gradual thinning of the oviductal wall and was responsible for the embryo transport impediment. In the second part of this project, we cultured primary mouse granulosa cells to characterize the roles of the Hippo signaling pathway during ovulation. We showed that protein kinase A is a key effector of Hippo activation following the luteinizing hormone (LH) surge. We then demonstrated that Yap1/Taz expression is required for the induction of several LH target genes. Using a chromatin immunoprecipitation experiment, we were able to show that YAP1 drives the expression of amphiregulin, a key paracrine transmitter of the LH signal, during the early events of ovulation. Together, these results identified new roles of the Hippo signaling pathway in the regulation of oviductal smooth muscle cells and of granulosa cells during ovulation. This thesis project opens the door to new avenues of investigation of Hippo involvement in the regulation of the female reproductive system.

<p dir="ltr">Nulliparous replacement beef heifers represent an opportunity to improve both genetic potential and lifetime production within the herd. However, advances in reproductive efficiency and synchrony in the herd require heifers to conceive earlier than multiparous cows in order to account for the extended postpartum interval following first-time parturition. Further, those heifers that achieve early calving dates continue to calve early throughout their lifetime. This early calving results in increased weaning weights and better synchrony in subsequent years. One obstacle producers face when breeding nulliparous heifers is the ability to identify which animals have reached puberty at the initiation of the breeding season. This results in the variation observed in synchronization success within a group of heifers. In Chapter 2 our laboratory formulated a study to analyze the efficacy of the 7-d CO-synch + CIDR protocol when utilizing short-term exposure to a progestin (melengestrol acetate, MGA) as a pre-synchronization protocol. Our hypothesis was that the heifers may respond more efficiently to an orally fed progestin as the increase in serum progesterone is less pronounced, when compared to the CIDR. This first study resulted in a protocol application error, in which MGA was fed an extra day (8 vs. 7). This additional day of treatment with MGA following the administration of a prostaglandin eliminated our laboratory’s opportunity to collect meaningful data from this first attempt. Thus, it was pertinent to restart the experiment in an attempt to obtain data for analysis. In order to avoid confounding data, half of the heifers in each treatment received a new treatment, while the other half remained on the treatment assigned during the first attempt. After completing the second round of experiments it was observed that at the first pregnancy check (study day 30), the heifers that were originally assigned to MGA, but were switched to a CIDR for the second attempt numerically outperformed their counterparts in the other three formulated treatment groups. In an attempt to replicate these results, a second study was formulated (Chapter 3), to mimic the timeline from the preliminary study. This resulted in a pre-synchronization treatment protocol prior to the initiation of the breeding season synchronization protocol. Previous studies that have been conducted with similar protocols were designed to provide heifers with a pre-synchronization period that would aid in the attainment of puberty prior to their first attempt at breeding through exposure to progesterone. The purpose of the Chapter 3 experiment was to evaluate the effects of feeding melengestrol acetate (MGA®) as a pre-synchronization for 10 days immediately prior to estrous synchronization and fixed-timed artificial insemination (FTAI). The ten days were chosen as this was a novel protocol that was the result of the preliminary study and the subsequent restart. Ninety-three crossbred heifers (395.67 ± 5.37 kg) were blocked by BW, genetics, and reproductive tract scores and allotted to 3 treatments. The 3 treatment groups were: 7-day CO-synch + CIDR without pre-synchronization (CON, n=31); 25 mg PGF2α (Lutalyse®) followed immediately by MGA feeding for 7 d prior to the start of the 7-day CO-synch + CIDR program (PRE, n=31); and 25 mg PGF2α followed immediately by MGA feeding for 7d followed 10 d later by the start of the 7-day CO-synch + CIDR program (PRE+10, n=31). The 7-day Co-synch + CIDR protocol in all three treatments was initiated on d 0 by administering a 2 cc IM injection of GnRH (Cystorelin®) and placing a CIDR into the vagina. The CIDRs were removed 7 days later and accompanied by 25 mg IM injection of PGF2α. An injection of GnRH occurred 60-66 hours following PGF2α at FTAI with frozen semen from a single bull. Ten days after FTAI, heifers were exposed to a bull. Estrotect® patches were applied throughout the study to assess estrous behavior. Ovaries were visualized by transrectal ultrasonography 24 hours post-FTAI to determine whether ovulation occurred. Pregnancy was determined on days 40, 64, and 109 post-FTAI via transrectal ultrasonography. Blood was collected via jugular venipuncture (d -19 and -12, MGA initiation and termination, days 0, 7, and 9) and serum progesterone determined. Performance data were analyzed using the MIXED procedure and conception data were analyzed using the GLIMMIX procedure of SAS. Heifers in the PRE+10 treatment group had higher levels of progesterone (P=0.04) at d 0 compared to PRE heifers. At d 7 (CIDR removal) there was a tendency (P=0.07) for PRE+10 heifers to have higher levels of progesterone than PRE, but did not differ by d 9 (FTAI, P=0.36). FTAI conception rates in heifers in the PRE treatment group (63%) tended (P = 0.09) to be higher compared to the controls (35%), but not different from PRE+10 (43%), with no differences in season-long pregnancy rates (P > 0.15). Pre-synchronization with MGA immediately prior to FTAI synchronization appears to increase conception rates early in the breeding season in beef heifers. In Chapter 4, our laboratory analyzed the efficacy of supplementation strategies post-insemination. Unlike the first two experiments, the third study focused on reproductive failure that occurs after insemination. The overarching goal remained the same, increasing the reproductive efficiency within our nulliparous heifer herd. A common practice for beef producers in the United States is to use estrous synchronization, and immediately turn heifers out to lush spring pasture immediately following FTAI. The fresh forage is high in water content which lowers dry matter intake (DMI) and creates a negative energy balance. Ultimately, this reduced energy intake can result in a reduction in reproductive performance. In the Chapter 4 our laboratory formulated a supplementation strategy utilizing the SmartFeed™ technology to deliver soybean hulls to our treatment group following insemination for 45 days. The utilization of the SmartFeed® technology provided the opportunity to analyze the efficacy of the supplementation strategy using each individual animal as an experimental unit. Sixty-two nulliparous crossbred heifers were fed in drylot to obtain moderate body condition prior to breeding at d 0 via FTAI and trained to utilize the SmartFeed™ system.Heifers were blocked by weight and body condition score to either the soybean hull supplementation group (SOY) or the non-supplemented control group (CON). . Heifers in the treatment group received their supplementation by entering the SmartFeed™ system, allowing for RFID controlled release of 2.27 kg. per head each day for 45 days. Scales located beneath each feed pan sent real time weight data for regulation and analysis on individual animal feeding behavior. On study d 6, a subset of the nulliparous crossbred heifers (n = 12; n = 6/ treatment) were transported by trailer from the Feldun Purdue Agricultural Center to Purdue West Lafayette main campus (approximately 217.74 km.). The subset of heifers had embryos flushed and evaluated for embryo quality and number of live/dead cells. Ultrasonography was utilized to monitor ovarian activity throughout the duration of the study and to determine pregnancy status 30 days after FTAI and 30 days after the 45-day breeding season. Though conception rates were not statistically (P=0.17) different (SOY 16/25; 64% vs. CON 11/25; 44%) when comparing treatment groups, the numerical differences suggest there is potential in pursuing a similar supplementation strategy following breeding in nulliparous beef heifers. The supplementation of SBH resulted in greater weight gain over time (P = 0.04), potentially explaining the numeric improvement in conception rate. The two pre-synchronization studies from Chapters 2 and 3 resulted in numerical improvements in conception rate as a result of exposing replacement heifers to a source of progestin prior to the initiation of their synchronization protocol. The implementation of progesterone priming mitigates the occurrence of short cycles and immature oocyte maturation at the time of ovulation. Based on results from previous studies conducted by our laboratory, the source of progestin greatly determines the timing and concentration of P4 circulating in replacement heifers immediately following treatment. Additionally, the 7 & 7 estrous synchronization protocol has grown in popularity and implementation. This protocol when broken down is very similar to the pre-synchronization protocol our laboratory utilized for the first two studies. Several studies have been conducted to analyze the efficacy of the 7 & 7 and the conception data was comparable to the MGA derived protocol. Thus, one potential direction for the future would be to formulate a research study that compares the two protocols. Since the conception rates were similar, it may be hypothesized that the MGA protocol could be more widely accepted as there is a reduction number of times animals are handled.</p>

A partir de données en population, nous avons: 1) évalué le risque de cardiopathies congénitales (CC) chez les fœtus conçus par assistance médicale à la procréation (AMP); et 2) déterminé les effets de l’AMP sur la prise en charge prénatale et le devenir périnatal des fœtus porteurs de CC. Nous avons observé que l'AMP était associée à une augmentation de 40% du risque de CC sans anomalies chromosomiques associées (OR ajusté = 1,4 IC95% 1,1-1,7). Nous avons également retrouvé qu'il existait des associations variables selon la catégorie de CC et la méthode d'AMP considérées. Nous avons observé que l'AMP était associée à une multiplication par 2,4 du risque de tétralogie de Fallot (OR ajusté = 2,4 IC95% 1,5-3,7), alors que nous n’avons pas retrouvé d’association statistiquement significative pour les trois autres CC spécifiques étudiées. Dans notre population, l'exposition à l'AMP ne semblait pas modifier le recours au diagnostic prénatal et à l'interruption médicale de grossesse chez les fœtus porteurs de CC comparés aux fœtus porteurs de CC conçus spontanément. Nous avons par ailleurs observé que le risque de prématurité des fœtus porteurs de CC conçus par AMP était environ 5 fois plus élevé que celui des fœtus porteurs de CC conçus spontanément (OR ajusté = 5,0 IC95% 2,9-8,6). En nous basant sur une méthodologie d'analyses de cheminement, nous avons retrouvé que les grossesses multiples contribuaient pour environ 20% au risque plus élevé de tétralogie de Fallot associé à l'AMP que nous avons observé. Enfin, les grossesses multiples contribuaient pour environ 2/3 du risque de prématurité associé à l'AMP chez les fœtus porteurs de CC. / Using population-Based data, we: 1) assessed the risk of congenital heart defects (CHD) in assisted reproductive techniques (ART) conceived fetuses; and 2) evaluated the effects of ART on prenatal management and perinatal outcomes of fetuses with CHD. We observed that ART were associated with a 40% increased risk of CHD without associated chromosomal anomalies (adjusted OR = 1.4 95%CI 1.1-1.7). We also found varying associations between the different methods of ART and categories of CHD. We observed that ART were associated with 2.4-Higher odds of tetralogy of Fallot (adjusted OR = 2.4 95%CI 1.5-3.7), whereas no statistically significant association was found for the three other specific CHD included. In our population, ART exposure did not seem to modify prenatal diagnosis and termination of pregnancy for fetal anomaly in fetuses with CHD compared to fetuses with CHD conceived spontaneously. The risk for premature birth in fetuses with CHD conceived following ART was 5-Fold higher as compared to fetuses with CHD conceived spontaneously (adjusted OR = 5.0 95%CI 2.9-8.6). Using a path-Analysis method, we found that multiple pregnancies contributed for about 20% to the higher risk of tetralogy of Fallot associated with ART that we had found. Finally, multiple pregnancies contributed for the 2/3 of the risk of premature birth associated with ART in fetuses with CHD.

Prolificacy in sheep, under most types of flock management, may exert an overwhelming influence on profitability. Three major classes of sheep farming are found in New Zealand, namely Extensive farming, on high country and droughty areas where wool is the chief product, Store sheep farming, on harder hill country, where income is derived from sales of both wool and surplus stock, and Fat lamb farming, in the easier and improved areas, where sales of fat stock almost exclusively dictate the size of the income. In all three types, ewe fertility is of paramount importance. This investigation was undertaken as a pilot attempt to demonstrate, with more accuracy, the source of, or reason for, the additional lambs which result from flushing ewes, in as far as this practice may increase both ovulation rate and subsequent mortality or merely reduce mortality in developing ova at some as yet underdefined stage of early pregnancy. The nature of the experiment was such that a study of the time-relationships of ovum loss and embryo mortality at various stages in early pregnancy could be made. Thus the matings of 225 ewes in two separate mobs were observed and slaughter dates were measured for individual ewes from mating times. By this means a considerable collection of both field and laboratory data was made available for a study of comparative individual and group reactions to the flushing treatment applied.