While growing up, Abisola Kehinde was fascinated by biology, one of those courses she didn’t have to study much to easily understand. It was natural to her, so choosing a career in science was a no-brainer. She was never told that, as a woman, there wasn’t space for her in this field. But there were other challenges related to gender biases.
The tools of assisted reproductive technologies (ART) have catalyzed remarkable developments in reproductive medicine. As a result, over five million babies have been born worldwide using ART since the first live birth derived from in vitro fertilization (IVF) in 1978. The prevalence of ART is largely a consequence of the high frequency of couples experiencing fertility difficulties (~15%) that can be treated by ART.
Our research goals are focused on genetic epigenetic investigations, at multiple levels of human development, related to the reproductive health of couples undergoing ART. My overall research program has been dedicated to understanding the roles genetics and epigenetics play in male infertility as well as in the negative outcomes of pregnancies derived from ART.
The objectives of my research program are diverse and include: (1) the identification and analysis of meiotic errors and its association with sperm aneuploidy and male infertility, and epigenetic modifications in male infertility; (2) the definition of the basal level of chromosomal abnormalities in pre-implantation embryos, and differentiation of the roles of meiotic and mitotic abnormalities in implantation failure in ART; (3) the examination of the potential genetic and epigenetic risks associated with ART pregnancies that may offer opportunities to develop unique strategies to prevent abnormal pregnancies after ART.
Study of chromosomal and epigenetic abnormalities after ICSI treatment for male infertility:
Intracytoplasmic sperm injection (ICSI) is an assisted reproductive procedure in treatment of male infertility. It involves the injection of a sperm into an oocyte to facilitate fertilization. Because natural barriers to fertilization are bypassed, ICSI may facilitate the transmission of genetic (DNA related) and epigenetic (DNA independent mechanisms that influence gene expression) abnormalities to the next generation. These abnormalities include a deviation from the normal complement of chromosomes (46 units of compacted DNA) in a cell. There is also concern that the injection procedure of ICSI disrupts the organization of the oocyte and this may affect the development of the resulting embryo. These alterations in pregnancies can potentially lead to pregnancy loss, birth defects, and low birth weight. We hypothesize that ICSI presents both procedure-dependent and independent risks to the fetus. We will investigate of the incidence of chromosomal abnormalities and epigenetic changes in the pregnancies of three assisted reproductive techniques - intrauterine insemination, in vitro fertilization (IVF), and ICSI - and evaluate how the differences among the techniques, namely the use of cell culture, the genetic background of different types of infertility involved, and the method of fertilization, effects the development of these abnormalities. Furthermore, we will examine key steps of cell division in the development of sperm when a chromosomal abnormality in a child is determined to be passed on from the father. Our long-term aims are to identify chromosomal and epigenetic risk factors to conceptions of ICSI, and to develop strategies to prevent abnormal offspring from being born after ICSI.
Investigation of meiotic and imprinting defects as an underlying cause of male factor infertility:
Infertility is regarded as a major health problem, affecting approximately one in six couples in Canada. It is estimated that 30-40% of couples seeking fertility treatments are diagnosed with male-factor infertility due to abnormal sperm production. In the majority of these cases, the cause of infertility remains unknown. It is suspected that genetic and epigenetic factors may both play an important role in the onset of male infertility. Recent ours and other studies have shown that errors in this meiotic division are more prevalent in infertile men and may play an important role in idiopathic male infertility. We recently provided evidence that meiotic errors in infertile men may also be associated with the production of aneuploid sperm, that is, sperm containing either extra or missing chromosomes. There is increasing evidence in the literature to suggest that infertile men may be at risk of having abnormal DNA methylation (a chemical modification of genetic sequences) in their sperm, which may affect sperm production. Recently, we also found that a subgroup of infertile men had increased imprinting defects (defects in the methylation of specific DNA sequences) in their sperm. We will use recently developed techniques to further characterize the meiotic defects that lead to the production of aneuploid sperm and male infertility in two unique infertile male groups (men with very low sperm counts with and without chromosome rearrangements). We will also investigate the prevalence of imprinting defects among infertile men, and its possible association with meiotic errors within the same study population. Detailed meiotic and imprinting studies of infertile men will begin to reveal the underlying genetic causes of male infertility. The results of this study could lead to improved treatment and reproductive outcomes for couples undergoing infertility treatments, such as intracytoplasmic sperm injection (ICSI).