Recruitment of doctoral students

	Thesis by:
	Lucille Berthet – INRAE, CNRS, Université de Tours
	Thesis supervision:
	Joëlle Dupont – INRAE, CNRS, Université de Tours

Thesis project abstract:

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder affecting 8-13% of women of childbearing age worldwide. In addition to representing one of the main causes of infertility in women, this pathology can alter menstrual cycles and cause acne, hyperpilosity, hair loss and weight gain, as well as increasing susceptibility to developing other health problems (diabetes, hypertension, hypercholesterolemia, heart disease, cancer).

Endocrine disruptors (EDs) are substances, natural or synthetic, that can interfere with hormone production and action in the body. New studies suggest that exposure to EPs may be a causal factor in PCOS.

The aims of Lucille Berthet’s thesis project are to identify the main EDs present in the follicular fluid ^[1] of PCOS patients, compared with non-PCOS patients, using a non-targeted mass spectrometry approach. The role of the main EDs identified will then be investigated in ovarian follicle cells, the granulosa cells. Effects on cell viability, proliferation and steroidogenesis ^[2] will be assessed individually, as well as in mixtures. This analysis will be carried out in vitro, on patient cells, as well as in vivo, in a rat model of spontaneously developing PCOS. This model will enable in-depth analysis of the effects of dietary exposure to EDs during gestation on female offspring, as well as on the production and quality of their gametes in adulthood.

The ambition of this research is to open up new perspectives in the management of PCOS patients.

^[1] Follicular fluid: a liquid rich in growth factors, nutrients, metabolites and hormones, present in the ovarian follicles in which the ovocytes develop.

^[2] Steroidogenesis: the process of synthesizing steroid hormones, which are involved in functions such as growth, metabolism and reproduction.

	Thesis by:
	Nastia Colin-Laignelet – Institut Cochin, Université de Paris
	Thesis supervision:
	Daniel Vaiman – Institut Cochin Catherine Patrat – Institut Cochin

Thesis project abstract:

Endometriosis is a chronic inflammatory gynecological disease, affecting around one in ten women. It is characterized by the implantation of cells resembling those of the inner layer of the uterus, outside the uterus, usually in the peritoneal cavity. Endometriosis leads to inflammatory reactions, with the formation of scar tissue and adhesions between neighbouring organs, as well as severe pain. Endometriosis is sometimes associated with infertility, and is one of its main causes.

The origins of this disease appear to be multifactorial, stemming from a complex interaction between genetics and environment. One gene in particular has been highlighted by a team at the Institut Cochin as a potential major player in familial cases of endometriosis.

Nastia Colin-Laignelet’s thesis project aims to study this gene in detail, in order to understand its functions and how its variability could impact biological mechanisms linked to endometriosis. An understanding of the mechanisms involved and their dysfunctions will enable action to be taken at both diagnostic and curative levels.

	Thesis by:
	Élisa Nied – CNRS, Université de Strasbourg
	Thesis supervision:
	Valérie Simonneaux – CNRS

Thesis project’s abstract:

Infertility is a major public health issue that can have a profound impact on the lives of those affected. Several studies indicate that a functional, well-synchronized biological clock is necessary for the proper functioning of female reproductive cycles and fertility. However, in industrialized societies, around 15% of women work staggered hours.

The aim of Élisa Nied’s thesis project is to study how shift work affects female reproductive health.

Using female mice as an animal model, this project tests the hypothesis that disruption of the light/dark cycle, as experienced by women working shifts, alters the function of the hypothalamic-pituitary-ovarian axis ^[1], which could lead to reduced fertility and impact on offspring development. This project also aims to develop different chronotherapeutic protocols ^[2] promoting resynchronization of the reproductive axis in female mice chronically exposed to time shifts, in order to improve their fertility.

^[1] Hypothalamic-pituitary-ovarian axis: pathway linking the hypothalamus, pituitary and ovaries. The hypothalamus releases a hormone to the pituitary which induces the latter to synthesize LH and FSH, hormones which act on the ovaries. The ovaries produce other hormones targeting, among others, the hypothalamus and pituitary gland.

^[2] Chronotherapy: approach aimed at administering a drug treatment at the best time of day or night, depending on its target and the biological rhythms associated with it. To find out more, read the Inserm article “À la bonne heure – C’est quoi la chronothérapie?” (in French only).

	Thesis by:
	Hugo Saavedra – Institut Curie, Université PSL
	Thesis supervision:
	Deborah Bourc’his – Inserm, Institut Curie

Thesis project’s abstract:

The development of an embryo begins with the activation of its genome and the acquisition of pluripotency, the property enabling cells to differentiate into other cell types and thus generate a complete organism.

These key events require epigenetic regulation of gene expression, i.e. the reorganization of chromatin, formed by DNA and its architect proteins called histones. However, the precise mechanisms by which histone marks ^[1] are interpreted and govern these processes after fertilization remain poorly understood.

Hugo Saavedra’s thesis project focuses on the role of a protein called SPIN1, a chromatin reader abundantly supplied to the embryo by the ovocyte at the time of fertilization. SPIN1 is a protein capable of recognizing various histone marks. The working hypothesis of this project is that SPIN1 would serve as a versatile platform, like a conductor of an orchestra, to coordinate gene expression via various chromatin pathways in the ovocyte and early embryo. These actions would then have crucial effects on the progression of embryonic development and, consequently, embryo viability and reproductive success.

^[1] Histone marks: modifications of histones (mainly by acetylation, methylation, phosphorylation or ubiquitination) enabling the recruitment of proteins capable of modifying chromatin structure.

	Thesis by:
	Cécilia Travagli-Chanal – Ined, Université de Picardie Jules Vernes
	Thesis supervision:
	Élise de La Rochebrochard – Ined Nathalie Le Bouteillec – Ined, Université de Picardie Jules Vernes

Thesis project’s abstract:

With 15 to 25% of couples of childbearing age affected, infertility represents a real public health problem. While advances such as medically assisted reproduction (MAP) bring hope, questions persist as to who can access these treatments. Research in the social sciences and humanities points out that marginalized populations, such as incarcerated women, face additional obstacles to reproductive health.
Since the January 18, 1994 law on public health and social protection, the health of people in prison has been overseen by the Ministry of Health. By law, this means that access to infertility treatments, such as MAP, must be the same in prison as in the community. However, the situation of imprisonment calls this ideal into question, since access to care involves a greater number of players (hospital, wardens, prison administration, gendarmerie, etc.). So, despite a legal framework guaranteeing equal access to healthcare, many obstacles stand in the way of access in detention.

Cécilia Travagli-Chanal’s thesis project aims to explore these obstacles, looking at both the rights of incarcerated people and institutional attitudes. The aim of this research is to study public policies on reproductive infertility and their effective transcription within the prison environment. Using qualitative methods, the study seeks to shed light on this under-explored issue, and to enrich and illuminate ethical debates on reproductive autonomy and social justice.