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Figure 1. Major early events for successful human reproduction. We study the mechanism(s) by which the RNA-binding protein, ZFP36L2 (L2), affect ovulation (A) and early embryo division (B). Failure of proper L2 regulation in these critical steps causes female infertility.

From ovulation through fertilization and ultimately embryo implantation, reproduction requires precise gene regulation at multiple levels. A critical and understudied aspect of reproductive gene regulation is modulation of mRNA function. Particularly important are the regulatory interactions of RNA-binding proteins with elements within the untranslated regions of messenger RNAs. We began this research theme by identifying an important functional connection between the RNA-binding protein Zinc Finger Protein 36 Like-2 (ZFP36L2 or L2) and female fertility (1). More recently, as an independent PI, my lab identified the first physiological and reproduction-related L2 target, i.e., the luteinizing hormone receptor (LHR) mRNA (2). LHR is well known to play key roles in reproductive biology, particularly during ovulation and oocyte maturation. Thus, one of our main goals in lab is to determine the biochemical basis for regulation of L2’s RNA-binding activity and how L2 controls LHR and potentially other transcripts during the ovarian cycle. Our findings may provide new tools and opportunities to improve clinical solutions for in vitro oocyte maturation, ovulation induction and age-related ovarian infertility. As of now we have focused primarily on the role of L2 in controlling LHR expression during ovulation (Fig. 1A). However, we also observed an effect of L2 on early embryo division (Fig. 1B), specifically in the progression of the embryo beyond the two-cell stage. In mouse, the initiation of zygotic gene transcription occurs during the transition from the initial cleavage step to the two-cell stage. During this brief window, there is a massive degradation of maternal mRNAs, by mechanisms that are presently unknown. Since L2 can destabilize certain mRNAs it is possible that L2 is involved in maternal RNA degradation and/or zygotic gene activation.

Ovulatory disorders and unexplained infertility encompass 50% of infertility cases.  Compounding the problem, over the last two decades in developed countries, there has been a trend towards delaying childbearing, which has contributed to an increase in age-related female infertility mainly of ovarian origin (3). Infertility is a global women’s health issue affecting 10-15% of the 1.5 billion women of reproductive age (4) and a major socio-economic matter because the majority of these women have no access to infertility treatment, and even in developed economies there are great inequalities in access to diagnosis and treatment (5).

 

A full list of the lab’s publications can be found here.

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The Triple E core values of our lab are: Embrace, Educate and Empower

The Ramos Lab is committed to embrace individuals from all backgrounds and groups, including, but not restricted to those from under-represented minorities. We consider the education process as being dynamic and transformative. In ways that that the unforeseen novel knowledge leads a to an empowered society.