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- Bodén, Ida
(author)
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The roles of the plasminogen activator and matrix metalloproteinase systems in ovulation and corpus luteum formation
- 2004
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Licentiate thesis (other academic/artistic)abstract
- Proteases of the plasminogen activator (PA) and the matrix metalloproteinase (MMP) enzyme systems are expressed in the ovulatory follicle and in the developing corpus luteum (CL). However, the functional role of these extracellular degrading protease systems in the ovulatory and CL development processes remains elusive. The first aim of this thesis was to develop a mouse model to study gonadotropin-induced CL formation. The second aim was to study the involvement of the PA and the MMP systems in gonadotropin-induced ovulation, and in CL formation and function.A mouse model for gonadotropin-induced CL formation was developed in order to control the timing of CL formation. In this model, immature mice were induced to ovulate by administrating gonadotropins and the endogenous prolactin surges were mimicked by administration of prolactin twice daily from day 2 of CL development. We observed that steroidogenic acute regulatory protein (StAR) mRNA was highly expressed at days 3 and day 6 of CL development and the levels remained high until late stages of CL regression.Since mice lacking plasminogen (plg-/-) only have a 14% reduction of ovulation efficiency, our hypothesis was that the MMP system could compensate for the loss of plasminogen. When administrating the MMP-inhibitor galardin to gonadotropin-primed ovulating mice, we found that wild-type mice (plg+/+ and C67BL/J6) and heterozygous mice (plg+/-) had an 18-20% reduction in ovulation efficiency as compared to untreated mice.Two models for CL formation, the adult pseudopregnant (psp) mouse model and a model whereby immature gonadotropin-primed mice were treated with prolactin, were used to study the formation and function of the CL in plg-/- mice treated with galardin. At day 3 of CL development, we found no alterations other than a slightly lower number of CL in plg-/- mice. This is most likely a secondary effect of the lower ovulation efficiency found in these mice. On the other hand, we found a 54% reduction in serum progesterone levels in plg-/- mice and a 37% reduction in the plg+/- mice as compared to wild type mice. At day 6 of CL development we saw a 45 % reduction of serum progesterone level in the plg-/- mice and a 22 % reduction in the plg+/- mice. A similar trend was observed at day 3 of CL development in immature gonadotropinprimed mice treated with prolactin. Galardin treatment did not alter the results significantly and the CLs were healthy and viable in these mice.In conclusion, our data suggest that both plasminogen and MMPs, alone or in combination, are dispensable for ovulation and for the formation of a viable CL under the conditions used in this study. The reduced serum progesterone levels observed in the plg-/- mice did not appear to be a result of defective CL formation. Instead, plasmin may have a novel role in the maintenance of luteal function. StAR expression may also be a good marker for CL development and regression in mice.
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- Domellöf, Erik, 1970-
(author)
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Stepping, placing and headturning biases in newborn infants : A neurodevelopmental perspective
- 2004
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Licentiate thesis (other academic/artistic)abstract
- In the present thesis the stepping, placing and head turning responses in healthy humanfullterm newborns are investigated. The main focus is put on a study of these newbornresponses in relation to functional asymmetries, while at the same time exploring anddiscussing different factors that possibly can affect the outcome of such studies. Study I aims to examine one such factor in relation to underlying mechanisms controlling leg movements in focusing on the effects of glucose on newborn stepping and placing responses. The results revealed that glucose, as well as an inactive state, resulted in less pronounced stepping responses and difficulties in eliciting them. There was also a tendency towards a similar finding for placing in that both glucose and an inactive state were associated with a less vigorous placing response, although this could not be proved significant. However, there was no effect of glucose on expressions of laterality in either ofthe responses studied. A theoretical debate in progress concerns whether different newborn functional asymmetries can be said representing a single neural system for lateralization or multiple sub-systems rooted in different neural mechanisms (Grattan, De Vos, Levy, & McClintock, 1992). In order to look closer at this issue in relation to newborn head- and leg preferences, Study II was designed to investigate the presence of side biases in newbornstepping and placing responses (lower-body), together with head turning preference (upperbody), and whether observed lateral biases of the upper- and lower body are congruent with each other. No evident lateral bias could be found for either response in terms of the first foot moved or direction of head turning. Furthermore, asymmetries in head turning did not correspond to asymmetries in leg movements, in support for multiple sub-systemsrather than a single lateralized system. However, a lateral bias was found for onset latency in relation to the first foot moved in both stepping and placing. The findings are discussed in relation to underlying neural mechanisms for lateral biases in leg movements and the important role of a thorough methodology in investigating newborn responses.
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