It has been recently found that some factors during intrauterine life are important and previously unsuspected determinants of cardiovascular disease decades later. The mechanisms are not yet clear but placental function in maintaining fetal nutrition and hormone secretion are likely to be important. Similar mechanisms have been found to affect female reproductive function and non-reproductive hormones in humans but the potential effects involving male reproductive health have not been studied s ....It has been recently found that some factors during intrauterine life are important and previously unsuspected determinants of cardiovascular disease decades later. The mechanisms are not yet clear but placental function in maintaining fetal nutrition and hormone secretion are likely to be important. Similar mechanisms have been found to affect female reproductive function and non-reproductive hormones in humans but the potential effects involving male reproductive health have not been studied so far. This project aims to search for prenatal factors that affect the development of the testis and prostate. By this means, prenatal factors may be an important in determining susceptibility to male infertility by lowering sperm output, androgen deficiency due to diminished testicular testosterone secretion and prostate disease notably prostatic hyperplasia. In this study we will employ our own specialised techniques for highly accurate measurement of the size of prostate zones and the testis using high frequency ultrasound. We will identify a birth cohort - a group of men born in a single hospital around 1970 - in whom we will measure prostate zones and testis size by ultrasound together with the hormonal markers relevant to the testis and prostate to examine whether any changes seen according to birthweight are due to concordant changes in hormones. This study could change the way in which disorders of male reproductive health are considered by focusing on factors occurring before and shortly after birth rather than on genetic or ambient environmntal factors in adult life which have been the overwhelming focus of research over recent decades.Read moreRead less
Cysteine-rich Secretory Protein Regulation Of Ion Channels In Male Fertility And Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$474,309.00
Summary
Diagnosis of the precise causes of male infertility and the development of male contraceptives requires improved understanding of sperm function. The Cysteine-Rich Secretory Proteins (CRISPs) are produced in the male reproductive tract where they regulate sperm function. Our project will demonstrate the essential requirement for CRISPs in sperm function and investigate their role in other tissues of the reproductive tract, including the prostate where they may be involved in prostate cancer.
Impairment of virilisation is one of the most common developmental defects in humans, yet over half the cases cannot be explained by our current knowledge. Studies of these processes is hindered because in most mammals virilisation occurs in the early fetus. Our recent studies using marsupials, where virilisation occurs after birth show that this process is mediated by 5-alpha-androstanediol, a hormone with previously undetermined physiological function. We will conduct experiments using tammar ....Impairment of virilisation is one of the most common developmental defects in humans, yet over half the cases cannot be explained by our current knowledge. Studies of these processes is hindered because in most mammals virilisation occurs in the early fetus. Our recent studies using marsupials, where virilisation occurs after birth show that this process is mediated by 5-alpha-androstanediol, a hormone with previously undetermined physiological function. We will conduct experiments using tammar wallabies and rabbits, to test 3 hypotheses about 5-alpha-androstanediol and specific enzymes in the developing reproductive tissues that either convert this hormone to active and inactive forms. The results of these experiments will direct testing for corresponding gene mutations in our collection of over 200 specimens from patients with defects of virilisation (pseudohemaphroditism) whose causes are still unknown. It is our expectation that the findings in these studies will provide insight not only into the pathways by which testicular hormones masculinize the developing male, but will also explain instances of male pseudohemaphroditism of unknown aetiology in humans.Read moreRead less
This Program Grant investigates a number of important reproductive problems that affect the fertility of men, prostate cancer and the way the mother nurtures and protects the baby during pregnancy. The successful development of sperm requires the proper function of a number of biological processes. This grant investigates the way in which sperm are produced, the genes that are needed to control their development, and the way sperm propel themselves and fertilize the egg. The research also invest ....This Program Grant investigates a number of important reproductive problems that affect the fertility of men, prostate cancer and the way the mother nurtures and protects the baby during pregnancy. The successful development of sperm requires the proper function of a number of biological processes. This grant investigates the way in which sperm are produced, the genes that are needed to control their development, and the way sperm propel themselves and fertilize the egg. The research also investigates how sperm are protected during their development from infection and immunological rejection, achieved in part by a special environment within the tubes in the testis where they grow. It appears that the general mechanisms that the body uses to combat infections are modified within the testis and the way in which this occurs may provide clues that could be applied to prevent the rejection of transplanted organs in general. Some of the substances that control these processes appear to play an important role in the body�s defense against infection. The grant also investigates the processes that are involved in the development of prostate cancer. These changes can occur over many years and the grant will study some substances that appear to be involved. The work will provide new knowledge that may assist in new tests to identify whether a cancer is slow or fast growing, thereby helping each man to decide the most sensible form of treatment. The grant will investigate how a group of proteins, that also are involved in the control of processes discussed above, assist the mother in protecting her baby during pregnancy. The outcomes will assist in the management of disturbances of pregnancy that may put the fetus at risk of survival.Read moreRead less