Page 7 - ASPIRE JANUARY 2023 Volume 8 / Issue 1

LL OF MISCARRIAGE
“We need to encourage and improve public and private investment in pregnancy research while developing a culture of offering participation in research to pregnant women,” he said.
“In many cases, miscarriage is not inevitable. Indeed, there are a number of treatment options that can reduce the occurrence of a miscarriage, for example progesterone treatment in high-risk women, heparin in women with antiphospholipid syndrome, and thyroxine to those with underactive thyroid disease.
“However, many miscarriages remain unexplained and there is an urgent need to research the aetiology of miscarriage comprehensively.
“For example, we need to better understand the role of the lining of the womb (endometrium) on miscarriage, the effect of the community of bacteria (‘microbiome’) in the vagina on miscarriage risk, and the effect of man’s sperm, for example sperm DNA fragmentation level, on miscarriage risk.”
ASPIRE 2023 ADELAIDE
Evolutionary genomics
advancing knowledge
of human biology
including reproduction
Evolutionary genomics will escalate our understanding of human biology, including reproduction, to new thresholds of discovery in the 21st century. Increasingly, scientists are applying evolutionary theory to study the interaction of factors that impact on human health, including environmental influences, genetic variations, diet, lifestyles and exposure to pathogens.
This issue will come under the microscope at the ASPIRE 2023 Congress in Adelaide through the keynote address of eminent ovarian physiologist Professor Aaron Hsueh, who has led a range of medical breakthroughs in his laboratory in the Department of Obstetrics and Gynaecology at Stanford University School of Medicine.
Professor Hsueh is also the author of the recently published book The Enlightenment of Evolutionary Medicine – The Past and Future of Human Diseases. His work will enlighten delegates to our 2023 Congress on the discovery of hormones and receptors based on evolutionary genomics.
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“The biggest breakthrough in biology in the 19th century was Charles Darwin’s theory of evolution, and the biggest breakthrough in biology in the 20th century was the sequencing of the human genome,” Professor Hsueh explained. “At the beginning of the 21st century, we can combine evolutionary theory with genomics to further understand biology and medicine.”
Professor Hsueh’s research includes the discovery of human placensin, a glucogenic hormone secreted by human placenta that is capable of promoting placental function. His team investigated hormonal regulation of granulosa cell functions leading to the establishment of a sensitive in vitro FSH bioassay.
“By applying the evolutionary principle, we designed a longacting follicle stimulating protein called ELONVA, which is now in clinical use for ovarian stimulation and oocyte retrieval,” Professor Hsueh said.
His laboratory has contributed to the understanding of ovarian follicle growth and atresia, intraovarian mechanisms of oocyte maturation, and autocrine/ paracrine regulation of early embryonic development.
Using evolutionary genomics, Professor Hsueh’s laboratory discovered many hormones and receptors, cloned human FSH and LH receptors together with five related receptors, naming them LGR 4 to 8, before identifying LGR 7 as the relaxin receptor and LGR 8 as the receptor for insulin-like peptide 3 (INSL3).
He also led breakthrough work on an in-vitro activation (IVA) method to actuate ovarian pre-antral follicles for the derivation of mature oocytes in patients with primary ovarian insufficiency and low ovarian reserve.
“We performed IVA by fragmenting the ovarian cortex of patients with primary ovarian insufficiency followed by transplants back to the patients resulting in follicle growth,” Professor Hsueh said. “The approach started as treatment for primary ovarian insufficiency and is now used for treating middle aged infertile women using in vivo incision of ovaries to promote follicle growth.”
In his pioneering work, Professor Hsueh has collaborated with colleagues in the Asia Pacific region including Professor Kazuhiro Kawamua in Japan on IVA development, Professor Chii-Ruey Tzeng in Taiwan on ovarian research, Professor Yingpu Sun in China on placensin, and Professor Ross Bathgate in Australia on characterisation of the INSL3 receptor.
“Understanding human medicine from an evolutionary perspective is my life-long goal,” Professor Hsueh said. “Evolutionary genomics analysis provides a new paradigm to pursue future discoveries in reproduction and all biomedical endeavours.”
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