L’implantation est caractérisée par les premiers contacts cellulaires permanents entre l’endomètre, tapissant l’utérus, et le conceptus (disque embryonnaire et tissus extra-embryonnaires). Cette étape se trouve être l’un des plus importants points de contrôle de la gestation nécessitant un dialogue finement régulé entre ces deux entités. Concernant les ruminants, un déclin de la fertilité a été observé notamment chez les vaches laitières hautes productrices. La moitié des gestations s’arrête pendant la période pré-implantatoire due à des mortalités embryonnaires précoces ainsi qu’à des défauts utérins. Depuis 10 ans, des analyses exploratoires ont été mises en place dans le but d’étudier les profils d’expression de gènes endométriaux sous l’influence du cycle oestral, de la gestation précoce ou encore des stéroïdes ovariens comme la progestérone et les oestrogènes. Ces études sont essentielles pour l’identification des gènes endométriaux clés pour la survie et la croissance du conceptus avant l’implantation. Notre laboratoire a réalisé une analyse transcriptomique à partir d’échantillons endométriaux collectés sur des vaches cycliques et gestantes au 20 ème jour post-oestrus correspondant respectivement à la phase folliculaire et au premier jour d’implantation. Plusieurs familles de facteurs de transcription apparaissent différentiellement exprimées dans cette étude, notamment FOXL2, un membre de la famille des Forkhead Box transcription factor considéré comme le gène clé de la différenciation ovarienne. Ce travail de thèse s’est intéressé à l’implication de FOXL2 dans la physiologie endométriale. FOXL2 est exprimé et régulé pendant le cycle oestral et la gestation précoce dans l’endomètre de ruminants. De plus, la progestérone a été identifiée comme le régulateur majeur de l’expression endométriale de FOXL2 chez la vache et la brebis alors que l’effet des estrogènes n’a pas été démontré. A partir d’une approche gènes candidats, la surexpression de FOXL2 induit la régulation différentielle de onze gènes potentiellement cibles de FOXL2 dans des cultures primaires endométriales de cellules stromales et épithéliales glandulaires. En particulier, PTGS2 qui est un gène impliqué dans la réceptivité utérine apparait inhibé par FOXL2 alors que SCARA5 et RSAD2, tout deux impliqués dans la réponse immunitaire sont stimulés. Enfin, DLX5 apparait différentiellement régulé entre les cellules stromales et épithéliales glandulaires sous l’impact d’une surexpression de FOXL2. Pour conclure, l’expression endométriale de FOXL2 est fortement liée au processus de réceptivité utérine qui se déroule avant l’implantation et peut moduler l’expression de gènes endométriaux essentiels. De nouvelles analyses sont nécessaires pour déterminer si FOXL2 est le gardien de la physiologie reproductive femelle. / Implantation is characterized by the first permanent cellular interactions between the endometrium, lining the uterus, and the conceptus (embryonic disk and extra-embryonic tissues) and appears to be one of the most important checkpoints of successful pregnancy. Regarding ruminant species, and more specifically dairy cows, half of pregnancies abort during the pre-implantation period due to early embryonic death and uterine defects. In the last decade, exploratory approaches have been developed to study endometrial genes expression under the influence of oestrous cycle, early pregnancy, and ovarian steroid hormones in order to identify systematically crucial endometrial genes for conceptus growth and survival leading to a successful implantation in ruminant specifically. A microarray analyse made at the laboratory based on endometrial samples collected from cyclic and pregnant cows at 20 days post-oestrous, corresponding respectively to the follicular phase and the implantation initiation. Several members of the transcription factor families appeared to be differentially expressed in this study including FOXL2, a member of the Forkhead box L sub-class originally considered as a key gene for ovarian differentiation. My PhD thesis focused on the implication of FOXL2 gene in endometrial physiology. FOXL2 gene had been demonstrated to be expressed and regulated during the oestrous cycle and early pregnancy in ruminant endometrium. Moreover, progesterone was identified as a master regulator of FOXL2 endometrial expression in both cattle and sheep whereas estrogens have no impact. Based on candidate genes approach, over-expression of FOXL2 gene induces a regulation of eleven putative FOXL2 target genes in primary endometrial stromal and glandular epithelial cells. In particular, PTGS2 which is a positive regulator gene for uterine receptivity was shown to be inhibited whereas SCARA5 and RSAD2 expressions that were involved in immune response were shown to be stimulated as well as DLX5 expression was differentially regulated between stromal and glandular epithelial cells. Collectively, FOXL2 endometrial expression is strongly linked to the uterine receptivity process prior to the implantation and modulates the expression of essential endometrial genes. Further investigations will be required to investigate whether FOXL2 is the gatekeeper of female reproduction in the vertebrate species.

Prostaglandins are integral mediators in reproductive processes but their exact role in uterine function is still not clear. In addition, ethical restraints have limited the availability of human tissue to investigate uterine prostanoid receptor populations. The aim of this thesis was to characterise the prostanoid receptors on the human and rat myometrium in order to evaluate the potential of the rat as an animal model of human uterine function and disease. For functional analysis of myometrial prostanoid receptors the immersion technique was utilised. LC-ESI-MS/MS was also used to measure the ex vivo myometrial release of prostanoid metabolites. The results show that both the rat and human uterus displays cyclical changes in uterine motility, with myogenicity greatest in the follicular and oestrus stages. The data also indicate that whilst the human uterus is responsive to EP3, EP2, TP, FP and IP receptor agonists, a functional population of only EP3, EP2 and FP receptors is present on the rat uterus, although the TP receptor appears to be upregulated at gestation and post-partum. The results also show that myometrial prostanoid release in the human uterus is cyclically regulated, with the greatest amount of prostaglandins being released during the late follicular stage. In conclusion, although similarities do exist with regard to the ovarian regulation of uterine motility in both the rat and human uterus, the differences in the apparent functional prostaglandin receptor populations between the two species suggest further work is required before the rat can be used as a model of human uterine function.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning). Uppsala : Sveriges lantbruksuniv., 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2006. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2006. / Härtill 5 uppsatser.

Diss. (sammanfattning). Uppsala : Sveriges lantbruksuniversitet, 2006. / Härtill 4 uppsatser.

As a contribution to the existing knowledge of grooming in primates five and a half years of grooming data were examined from a group of free-living chimpanzees (Pan troglodytes) in the Budongo Forest, Uganda, to investigate various functional significances of grooming behaviour within the context of social reinforcement. The fission–fusion social structure of chimpanzees results in group members not moving around as a single unit, but forming temporary units as the need arises. This reduces opportunities for individuals to groom others and therefore, based on time and association constraints alone, grooming was as expected found to be unevenly distributed among group members. Grooming patterns found among this group of chimpanzees were comparable to those observed in other free-living populations with variations possibly being attributed to resource base, population numbers and differences in age-sex class composition. One of the suggested social benefits of grooming is that it is used to enhance reproductive success, either by allowing males to enhance their proximity to oestrous females, or by influencing female choice through the development of affiliative relationships with males. Grooming was found to increase between males and females, whilst females displayed sexual receptivity through the presence of anogenital swellings and grooming may be a strategy used by males to increase their access to copulation opportunities, whereas females may use grooming to increase protection from harassment by less preferred males during swollen periods and also increase the likelihood of copulation with preferred partners. Based on the availability of oestrous females, copulations between males and adult females occurred significantly less frequently than expected, whereas copulations between males and subadult females occurred significantly more frequently than expected. Overall a positive correlation was found between grooming of females by males and frequency of copulations. Due to concerns regarding the validity of different sampling methods, scan-focal and ad libitum sampling methods were compared to establish if results from different sampling methods were similar. Results from the scan-focal and ad libitum sampling methods had very few discrepancies, and it is suggested that ad libitum sampling methods which record behaviour types whenever they occur, may be more beneficial for species which don’t move around as a single unit and live in environments where visibility is reduced, therefore increasing the possibility of recording individuals or behaviours that are observed infrequently. Scan-focal sampling may be more beneficial in studying species which move around together in habitats which are conducive to greater visibility, therefore allowing all or most group members to be observed simultaneously. / Thesis (DPhil)--University of Pretoria, 2009. / Zoology and Entomology / unrestricted

Prostaglandins are integral mediators in reproductive processes but their exact role in uterine function is still not clear. In addition, ethical restraints have limited the availability of human tissue to investigate uterine prostanoid receptor populations. The aim of this thesis was to characterise the prostanoid receptors on the human and rat myometrium in order to evaluate the potential of the rat as an animal model of human uterine function and disease. For functional analysis of myometrial prostanoid receptors the immersion technique was utilised. LC-ESI-MS/MS was also used to measure the ex vivo myometrial release of prostanoid metabolites. The results show that both the rat and human uterus displays cyclical changes in uterine motility, with myogenicity greatest in the follicular and oestrus stages. The data also indicate that whilst the human uterus is responsive to EP3, EP2, TP, FP and IP receptor agonists, a functional population of only EP3, EP2 and FP receptors is present on the rat uterus, although the TP receptor appears to be upregulated at gestation and post-partum. The results also show that myometrial prostanoid release in the human uterus is cyclically regulated, with the greatest amount of prostaglandins being released during the late follicular stage. In conclusion, although similarities do exist with regard to the ovarian regulation of uterine motility in both the rat and human uterus, the differences in the apparent functional prostaglandin receptor populations between the two species suggest further work is required before the rat can be used as a model of human uterine function. / Allergan Inc