Male Infertility And Defective Sperm-oocyte Interaction
Funder
National Health and Medical Research Council
Funding Amount
$244,614.00
Summary
Infertility affects 15% of people and although not usually ill, they are extremely distressed by the condition. In vitro fertilisation (IVF) with normal sperm and intracytoplasmic sperm injection for sperm defects, can assist such patients have a family, but these treatments are expensive and not always successful. The causes of male infertility are largely unknown, diagnostic methods are crude and there is usually no treatment to promote natural conception. Conventional semen analysis provides ....Infertility affects 15% of people and although not usually ill, they are extremely distressed by the condition. In vitro fertilisation (IVF) with normal sperm and intracytoplasmic sperm injection for sperm defects, can assist such patients have a family, but these treatments are expensive and not always successful. The causes of male infertility are largely unknown, diagnostic methods are crude and there is usually no treatment to promote natural conception. Conventional semen analysis provides limited information on fertilising ability. Our work over 15 years has shown that many patients go undiagnosed, particularly those with defects impairing fertilisation. During human fertilisation, sperm bind to the zona pellucida, a coat around the egg, via the membrane over a cap like structure on the sperm head called the acrosome. Binding of a sperm triggers the acrosome reaction, the process by which the membranes covering the acrosome fuse and the acrosomal contents are released. The sperm then penetrates the zona pellucida, binds to the membrane of the egg and is taken into the cytoplasm. We have developed tests to assess sperm binding to the zona pellucida and the acrosome reaction using eggs that failed to fertilise during clinical IVF. These tests show defects of sperm binding to the zona pellucida and the zona pellucida induced acrosome reaction are present in over 25% of patients without other obvious causes for their infertility. The men are severely infertile but have normal sperm by conventional tests. In this project we will determine if there are changes in membrane proteins in sperm which do not bind to the zona pellucida or undergo the acrosome reaction. We will categorise patients on the responses of their sperm to activation of key enzymes and other regulatory molecules involved in the fertilisation process. This will allow us to select subjects for further examination of protein abnormalities and genetic causes of the conditions.Read moreRead less
Robert McLachlan is an internationally recognised clinician-scientist in male reproductive health. His basic research examines the genetic & endocrine regulation of sperm production. His clinical studies span male fertility regulation, the use of assisted reproductive treatments, and the evidence-based use of androgen replacement. As Director of Andrology Australia, he has a leading national role in professional and community education, developing research capacity and male health advocacy.
Role Of Stem-progenitor Cells In Endometrial Regeneration And Endometriosis
Funder
National Health and Medical Research Council
Funding Amount
$437,720.00
Summary
We have discovered 2 types of adult stem cells in the lining of the uterus (endometrium) that are likely responsible for its ability to grow a new lining each month. This project aims to determine if endometrial stem cells are shed into the pelvic cavity during menstruation to cause endometriosis, a common, chronic disorder affecting 6-15% of women during their reproductive years and for which treatments are suboptimal. This knowledge may change how endometriosis will be treated in the future.
Facilitating Endometrial Receptivity To Improve Pregnancy Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$734,252.00
Summary
The womb prepares itself in each menstrual cycle for pregnancy and the implantation of an embryo. In some women, the endometrium may not prepare itself adequately and this can lead to infertility. We have identified small RNA that may be useful in predicting which women are not adequately prepared for implantation and may be used to develop treatments for infertile women, for which there are currently no treatments.
Mechanisms And Utilisation Of IFN-epsilon-mediated Protection Against Chlamydia Reproductive Tract Infection
Funder
National Health and Medical Research Council
Funding Amount
$750,486.00
Summary
Chlamydia is a common cause of sexually transmitted diseases resulting in pelvic inflammatory disease, infertility and ectopic pregnancy. There are no vaccines that prevent infection or disease. We have discovered a new factor in the immune system (interferon-epsilon) that only occurs in the reproductive tract. If this factor is absent then Chlamydia infections are more severe. We will investigate how this factor protects against infection and if we can use it as a new agent against Chlamydia ST ....Chlamydia is a common cause of sexually transmitted diseases resulting in pelvic inflammatory disease, infertility and ectopic pregnancy. There are no vaccines that prevent infection or disease. We have discovered a new factor in the immune system (interferon-epsilon) that only occurs in the reproductive tract. If this factor is absent then Chlamydia infections are more severe. We will investigate how this factor protects against infection and if we can use it as a new agent against Chlamydia STDs.Read moreRead less
A Novel Reproductive Tract Factor That Protects Against Chlamydia
Funder
National Health and Medical Research Council
Funding Amount
$541,133.00
Summary
Chlamydia is a common cause of sexually transmitted diseases resulting in pelvic inflammatory disease, infertility and ectopic pregnancy. There are no vaccines that prevent infection or disease. We have discovered a new factor in the immune system (interferon-epsilon) that only occurs in the reproductive tract. If this factor is absent then Chlamydia infections are more severe. We will investigate how this factor protects against infection and if we can use it as a new agent against Chlamydia ST ....Chlamydia is a common cause of sexually transmitted diseases resulting in pelvic inflammatory disease, infertility and ectopic pregnancy. There are no vaccines that prevent infection or disease. We have discovered a new factor in the immune system (interferon-epsilon) that only occurs in the reproductive tract. If this factor is absent then Chlamydia infections are more severe. We will investigate how this factor protects against infection and if we can use it as a new agent against Chlamydia STDs.Read moreRead less
Endogenous Oestrogen Is A Key Missing Link In Urethral Hypospadias
Funder
National Health and Medical Research Council
Funding Amount
$456,467.00
Summary
Defects in penis development are among the most common birth abnormalities, and affect around 1 in every 150 live male births in Australia. Development of the penis is known to be driven by male hormones (androgens), but we have recently shown that oestrogen also plays a role in this process. This project will define the role of estrogen in penis development and how a loss or gain of estrogens can cause developmental defects.
Role Of The Histone Variant H3.3 In Germ Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$581,223.00
Summary
Over their life cycle, germ cells are unique in undergoing a large scale reformatting of their gene or DNA control systems, required for their own development, and for the development of the fertilized egg. We think that the protein ïhistone H3.3Í is crucial to this reformatting process. We will test this possibility by determining how much H3.3 is present in germ cells. Also, we will make mice which lack this protein in germ cells to see if this affects the reformatting process.