Molecular Reproduction and Development最新文献

In addition to widely recognized contributions of the paternal genome, centriole, and oocyte-activation factors, sperm deliver a wide range of macromolecules to the fertilized embryo. The impacts of these factors on the embryo, progeny, and even subsequent generations have become increasingly apparent, along with an understanding of an extensive potential for male health and environmental exposures to exert both immediate and long-term impacts on mammalian reproduction. Available data reveal that sperm factors interact with and regulate the actions of oocyte factors as well as exerting additional direct effects on the early embryo. This review provides a summary of the nature and mechanisms of paternal effects in early mammalian embryos, long-term effects in progeny, susceptibility of sperm components to diverse environmental factors, and potential approaches to mitigate adverse effects of such exposures.

Müllerian ducts (MD), also known as paramesonephric ducts, are the primordial anlage of the female reproductive tract organs including the oviduct, uterus, cervix and upper vagina along the craniocaudal axis. Although the general architecture of MD-derived organs is conserved, each organ possesses their unique epithelial structures and cell types to confer their region-specific functions, which collectively coordinate successful fertilization and pregnancy. MD epithelial fate decisions and differentiation along the craniocaudal axis is dependent on spatiotemporal regulation of intrinsic transcription factors and extrinsic signals derived from the mesenchyme. Findings from genetic mouse models, single-cell sequencing studies, and organoid cultures have significantly advanced our understanding of the cellular and molecular mechanisms of MD regionalization. In this review, we first discuss the diversity of epithelial morphologies and cell types in the female reproductive tract organs. Then, we discuss the roles of key transcription factors (Hox, transcriptional cascade driving multiciliogenesis, Foxa2, and P63), signaling pathways (estrogen/ESR1, Wnt/β-catenin, hedgehog, and retinoic acid), and epigenetic factors (microRNAs, chromatin remodeling factors, and histone modification enzymes) in region-specific MD differentiation. Further deciphering molecular mechanisms of MD craniocaudal patterning will open new avenues to improve our strategies for prevention, diagnosis, and treatment of Müllerian anomalies and female reproductive tract disorders.

High doses of follicle stimulating hormone (FSH) are used during ovarian stimulation to maximize the number of oocytes recovered for in vitro fertilization (IVF) during assisted reproductive technology (ART) in women. Whether high FSH doses are detrimental to embryo viability remains controversial. Evidence from many clinical studies revealed that FSH dose is inversely correlated with live birth rate in women. The mechanistic basis for this effect has been elusive. This review summarizes over 20 years of work using a unique biomedical model, the small ovarian reserve heifer (SORH). Those studies revealed that excessive FSH doses can disrupt gene expression via multiple cell-signaling pathways in ovarian cells, resulting in follicular hyperstimulation dysgenesis (FHD). This compromises the capacity of ovulatory-size follicles to respond to gonadotropins, produce estradiol and ovulate, causes premature cumulus expansion and oocyte maturation, and impairs the fertilizability of oocytes. The SORH model has thus provided new insights into the nature and mechanisms of the deleterious effects of excessive FSH doses during ovarian stimulation. The SORH model has been and remains valuable for basic research and for the discovery of ways to optimize FSH dosing clinically to improve IVF success and ART outcomes.

A role for the plasminogen activator (PA) system has been postulated in mammalian gonads, considering the complex process of morphogenesis these organs undergo during their development. Our results show that mouse Sertoli cells under basal conditions produce both types of PA, tissue-type PA (tPA) and urokinase-type PA (uPA), and hormonal treatments increase the production of both enzymes. The increased enzyme secretion does not correlate with a parallel increase in their mRNAs. However, the proteolytic activity results from a balance between enzyme activity and inhibitors. Hormonal stimulation decreased the expression of the inhibitor PAI-1, suggesting that the increase in proteolytic activity might depend on the decreased production of PAI-1.

The expression of the two enzymes and their inhibitor depends on the seminiferous epithelium stage. We observed higher uPA mRNA levels at stages VII-VIII and IX-XII, tPA peaks at stages VII-VIII, and PAI-1 mRNA levels decreased at stages VII-VIII and IX-XII.

The testes from mice lacking the uPA gene (uPA^−/−) presented statistically smaller sizes and weights. Histological analysis of uPA^−/−animals showed tubular morphology defects and atypical residual bodies (RB), suggesting a defect in Sertoli cell phagocytosis. Moreover, we show lower sperm concentration and motility in uPA^−/− mice. These data suggested an effective deficiency of testicular development in the absence of uPA.

Echinoderms exhibit a wide range of reproductive strategies as adaptations to variable environments. The processes of gonadal development, germ cell differentiation, and spermatogenesis in echinoderms are crucial physiological processes that warrant further in-depth exploration. This review systematically summarizes research from early basic sciences to recent studies on male gonadal development and spermatogenesis, encompassing morphology, histology, physiology, cell biology, developmental biology, and evolutionary biology. We introduce the structural and cellular similarities and differences among model or non-model organisms from five classes of echinoderms to provide insights for future comparative research between higher vertebrates and lower organisms. The regulatory systems involved in echinoderm spermatogenesis are described from various aspects including nutritional supply, environmental factors, neurological influences, endocrinological influences, and hormonal influences. This article aims to elucidate gonadal development and spermatogenesis in echinoderms—organisms at unique evolutionary nodes—providing valuable materials for studying adaptive evolution and developmental biology. Additionally, a comprehensive summary of characterized genes and gene markers associated with testes development and spermatogenesis is provided as useful information for future systematic studies on cell subpopulations. Future studies can focus on molecular changes associated with chromatin remodeling during germ cell development, cellular differentiation, and intercellular communication mediated by receptor-ligand interactions, to further our understanding of biological processes and regulatory networks involved in echinoderm gonadal development and spermatogenesis.

Odourant receptors (ORs) are not restricted only to the nose, but also occur in many other organs and tissues, including the reproductive system. In fact, ORs are the most heavily expressed in testis than in any other extra-nasal tissue. Accumulating evidence suggests that olfactory and reproductive systems are both structurally and functionally linked and that these interconnections can influence various aspects of reproduction. In this article, we first review our current understanding of these interconnections and then collate accumulated evidence on the presence of ORs in the male reproductive system and sperm cells. We then investigate the potential role of female reproductive tract odourants in sperm chemotaxis and selection. Finally, since the existing evidence especially for sperm odor sensing capability and its physiological function are controversial, we also review potential reasons for the controversy and propose some ways to resolve the debate. Collectively, we conclude that reproductive odourant signaling may play an important, although currently largely unclear role in many key processes directly related to male fertility. However, since we lack holistic understanding of the functional significance of ORs and odor sensing pathways of the male reproductive system, more empirical research is warranted.